Pub Date : 2024-07-03DOI: 10.2174/0118715206302216240628072554
Salma Batool, Laiba Asim, Fawad Raffaq Qureshi, Ammara Masood, Maria Mushtaq, Rahman Shah Zaib Saleem
Liver and Breast cancer are ranked as the most prevailing cancers that cause high cancer-related mortality. As cancer is a life-threatening disease that affects the human population globally, there is a need to develop novel therapies. Among the available treatment options include radiotherapy, chemotherapy, surgery, and immunotherapy. The most superlative modern method is the use of plant-derived anticancer drugs that target the cancerous cells and inhibit their proliferation. Plant-derived compounds are generally considered safer than synthetic drugs/traditional therapies and could serve as potential novel targets to treat liver and breast cancer to revolutionize cancer treatment. Alkaloids and Polyphenols have been shown to act as anticancer agents through molecular approaches. They disrupt various cellular mechanisms, inhibit the production of cyclins and CDKs to arrest the cell cycle, and activate the DNA repairing mechanism by upregulating p53, p21, and p38 expression. In severe cases, when no repair is possible, they induce apoptosis in liver and breast cancer cells by activating caspase-3, 8, and 9 and increasing the Bax/Bcl-2 ratio. They also deactivate several signaling pathways, such as PI3K/AKT/mTOR, STAT3, NF-kB, Shh, MAPK/ERK, and Wnt/β-catenin pathways, to control cancer cell progression and metastasis. The highlights of this review are the regulation of specific protein expressions that are crucial in cancer, such as in HER2 over-expressing breast cancer cells; alkaloids and polyphenols have been reported to reduce HER2 as well as MMP expression. This study reviewed more than 40 of the plant-based alkaloids and polyphenols with specific molecular targets against liver and breast cancer. Among them, Oxymatrine, Hirsutine, Piperine, Solamargine, and Brucine are currently under clinical trials by qualifying as potent anticancer agents due to lesser side effects. As a lot of research is there on anticancer compounds, there is a desideratum to compile data to move towards clinical trials phase 4 and control the prevalence of liver and breast cancer.
{"title":"Molecular Targets of Plant-based Alkaloids and Polyphenolics in Liver and Breast Cancer- An Insight into Anticancer Drug Development.","authors":"Salma Batool, Laiba Asim, Fawad Raffaq Qureshi, Ammara Masood, Maria Mushtaq, Rahman Shah Zaib Saleem","doi":"10.2174/0118715206302216240628072554","DOIUrl":"https://doi.org/10.2174/0118715206302216240628072554","url":null,"abstract":"<p><p>Liver and Breast cancer are ranked as the most prevailing cancers that cause high cancer-related mortality. As cancer is a life-threatening disease that affects the human population globally, there is a need to develop novel therapies. Among the available treatment options include radiotherapy, chemotherapy, surgery, and immunotherapy. The most superlative modern method is the use of plant-derived anticancer drugs that target the cancerous cells and inhibit their proliferation. Plant-derived compounds are generally considered safer than synthetic drugs/traditional therapies and could serve as potential novel targets to treat liver and breast cancer to revolutionize cancer treatment. Alkaloids and Polyphenols have been shown to act as anticancer agents through molecular approaches. They disrupt various cellular mechanisms, inhibit the production of cyclins and CDKs to arrest the cell cycle, and activate the DNA repairing mechanism by upregulating p53, p21, and p38 expression. In severe cases, when no repair is possible, they induce apoptosis in liver and breast cancer cells by activating caspase-3, 8, and 9 and increasing the Bax/Bcl-2 ratio. They also deactivate several signaling pathways, such as PI3K/AKT/mTOR, STAT3, NF-kB, Shh, MAPK/ERK, and Wnt/β-catenin pathways, to control cancer cell progression and metastasis. The highlights of this review are the regulation of specific protein expressions that are crucial in cancer, such as in HER2 over-expressing breast cancer cells; alkaloids and polyphenols have been reported to reduce HER2 as well as MMP expression. This study reviewed more than 40 of the plant-based alkaloids and polyphenols with specific molecular targets against liver and breast cancer. Among them, Oxymatrine, Hirsutine, Piperine, Solamargine, and Brucine are currently under clinical trials by qualifying as potent anticancer agents due to lesser side effects. As a lot of research is there on anticancer compounds, there is a desideratum to compile data to move towards clinical trials phase 4 and control the prevalence of liver and breast cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oral Squamous Cell Carcinoma (OSCC) is the most common cancer arising from squamous epithelium in the oral cavity and is characterized by high aggressiveness and metastatic potential, which together with a late diagnosis results in a 5-year survival rate of only 50% of patients. The therapeutic options for OSCC management are limited and largely influenced by the cancer stage. While radical surgery can be curative in early stage of disease, most cases require adjuvant therapies, including chemotherapy and radiotherapy which, however, often achieve poor curative rates and are associated with important negative effects. Therefore, there is an urgent need to discover new alternative treatment strategies to improve patients' outcomes. Several medicinal herbs are being studied for their preventive or therapeutic effect in several diseases, including cancer. In particular, the Indian spice curcumin, largely used in oriental countries, has been studied as a chemopreventive or adjuvant agent for different malignancies. Indeed, curcumin is characterized by important biological properties, including antioxidant, anti-inflammatory, and anticancer effects, which could also be exploited in OSCC. However, due to its limited bioavailability and poor aqueous solubility, this review is focused on studies designing new synthetic analogues and developing novel types of curcumin delivery systems to improve its pharmacokinetic and biological properties. Thus, this review analyses the potential therapeutic role of curcumin in OSCC by providing an overview of current in vitro and in vivo studies demonstrating the beneficial effects of curcumin and its analogues in OSCC.
{"title":"Curcumin and its Analogues in Oral Squamous Cell Carcinoma: State-of-the-art and Therapeutic Potential.","authors":"Valentina Schiavoni, Monica Emanuelli, Davide Sartini, Eleonora Salvolini, Valentina Pozzi, Roberto Campagna","doi":"10.2174/0118715206297840240510063330","DOIUrl":"https://doi.org/10.2174/0118715206297840240510063330","url":null,"abstract":"<p><p>Oral Squamous Cell Carcinoma (OSCC) is the most common cancer arising from squamous epithelium in the oral cavity and is characterized by high aggressiveness and metastatic potential, which together with a late diagnosis results in a 5-year survival rate of only 50% of patients. The therapeutic options for OSCC management are limited and largely influenced by the cancer stage. While radical surgery can be curative in early stage of disease, most cases require adjuvant therapies, including chemotherapy and radiotherapy which, however, often achieve poor curative rates and are associated with important negative effects. Therefore, there is an urgent need to discover new alternative treatment strategies to improve patients' outcomes. Several medicinal herbs are being studied for their preventive or therapeutic effect in several diseases, including cancer. In particular, the Indian spice curcumin, largely used in oriental countries, has been studied as a chemopreventive or adjuvant agent for different malignancies. Indeed, curcumin is characterized by important biological properties, including antioxidant, anti-inflammatory, and anticancer effects, which could also be exploited in OSCC. However, due to its limited bioavailability and poor aqueous solubility, this review is focused on studies designing new synthetic analogues and developing novel types of curcumin delivery systems to improve its pharmacokinetic and biological properties. Thus, this review analyses the potential therapeutic role of curcumin in OSCC by providing an overview of current in vitro and in vivo studies demonstrating the beneficial effects of curcumin and its analogues in OSCC.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-30DOI: 10.2174/0118715206299407240324110505
Rafat M. Mohareb, Rehab A. Ibrahim, Fatma O. Al Farouk, Ensaf S. Alwan
Background:: Xanthenes and benzoxanthenesare are highly valuable compounds in organic chemistry and medicinal chemistry. Xanthene derivatives were found to have many applications in medicinal chemistry. Objective:: This work aims to explore the synthesis of xanthene derivatives with various substituents and find the possibility of their uses as anticancer agents. Method:: The basic starting compound through this work was the 2,3-dihydro-1H-xanthen-1-one (3), which was synthesized from the reaction of cyclohexan-1,3-dione and 2-hydroxybenzaldehyde. Compound 3 synthesized new thiophene, pyrimidine, isoxazole, and thiazole derivatives based on the xanthenes nucleus. Fused xanthene derivatives were obtained through further heterocyclization reactions. Multicomponent reactions expressed in this work were carried out in the presence of solvent catalyzed by Et3N and in solvent-free ionic liquid immobilized catalyst. Results:: Cytotoxicity for the newly synthesized compounds toward cancer cell lines was measured, and the results revealed that many compounds exhibited high inhibitions. Conclusion:: The antiproliferative activity of the synthesized compounds was studied on six selected cancer cell lines. The nature of the heterocyclic ring and the variations of substituted groups showed a high effect through the inhibitions of the tested compound.
{"title":"Ionic Liquids Immobilized Synthesis of New Xanthenes Derivatives and their Antiproliferative, Molecular Docking, and Morphological Studies","authors":"Rafat M. Mohareb, Rehab A. Ibrahim, Fatma O. Al Farouk, Ensaf S. Alwan","doi":"10.2174/0118715206299407240324110505","DOIUrl":"https://doi.org/10.2174/0118715206299407240324110505","url":null,"abstract":"Background:: Xanthenes and benzoxanthenesare are highly valuable compounds in organic chemistry and medicinal chemistry. Xanthene derivatives were found to have many applications in medicinal chemistry. Objective:: This work aims to explore the synthesis of xanthene derivatives with various substituents and find the possibility of their uses as anticancer agents. Method:: The basic starting compound through this work was the 2,3-dihydro-1H-xanthen-1-one (3), which was synthesized from the reaction of cyclohexan-1,3-dione and 2-hydroxybenzaldehyde. Compound 3 synthesized new thiophene, pyrimidine, isoxazole, and thiazole derivatives based on the xanthenes nucleus. Fused xanthene derivatives were obtained through further heterocyclization reactions. Multicomponent reactions expressed in this work were carried out in the presence of solvent catalyzed by Et3N and in solvent-free ionic liquid immobilized catalyst. Results:: Cytotoxicity for the newly synthesized compounds toward cancer cell lines was measured, and the results revealed that many compounds exhibited high inhibitions. Conclusion:: The antiproliferative activity of the synthesized compounds was studied on six selected cancer cell lines. The nature of the heterocyclic ring and the variations of substituted groups showed a high effect through the inhibitions of the tested compound.","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-30DOI: 10.2174/0118715206289666240423091244
Yanfang Zhao, Wanbao Ding, Peixian Zhang, Lei Deng, Yi Long, Jiuqin Lu, Fereshteh Shiri, Mostafa Heidari Majd
Background: Although tamoxifen (TMX) belongs to selective estrogen receptor modulators (SERMs) and selectively binds to estrogen receptors, it affects other estrogen-producing tissues due to passive diffusion and non-differentiation of normal and cancerous cells and leads to side effects. Methods: The problems expressed about tamoxifen (TMX) encouraged us to design a new drug delivery system based on magnetic nanoparticles (MNPs) to simultaneously target two receptors on cancer cells through folic acid (FA) and hyaluronic acid (HA) groups. The mediator of binding of two targeting agents to MNPs is a polymer linker, including dopamine, polyethylene glycol, and terminal amine (DPN). Results: Zeta potential, dynamic light scattering (DLS), and Field emission scanning electron microscopy (FESEM) methods confirmed that MNPs-DPN-HA-FA has a suitable size of ~105 nm and a surface charge of -41 mV, and therefore, it can be a suitable option for carrying TMX and increasing its solubility. The cytotoxic test showed that the highest concentration of MNPs-DPN-HA-FA-TMX decreased cell viability to about 11% after 72 h of exposure compared to the control. While the protective effect of modified MNPs on normal cells was evident, unlike tamoxifen, the survival rate of liver cells, even after 180 min of treatment, was not significantly different from the control group. The protective effect of MNPs was also confirmed by examining the amount of malondialdehyde, and no significant difference was observed in the amount of lipid peroxidation caused by modified MNPs compared to the control. Flow cytometry proved that TMX can induce apoptosis by targeting MNPs. Real-time PCR showed that the modified MNPs activated the intrinsic and extrinsic mitochondrial pathways of apoptosis, so the Bak1/Bclx ratio for MNPs-DPN-HA-FA-TMX and free TMX was 70.82 and 0.38, respectively. Also, the expression of the caspase-3 gene increased 430 times compared to the control. On the other hand, only TNF gene expression, which is responsible for metastasis in some tumors, was decreased by both free TMX and MNPs-DPN-HA-FA-TMX. Finally, molecular docking proved that MNPs-DPN-HA-FA-TMX could provide a very stable interaction with both CD44 and folate receptors, induce apoptosis in cancer cells, and reduce hepatotoxicity. Conclusion: All the results showed that MNPs-DPN-HA-FA-TMX can show good affinity to cancer cells using targeting agents and induce apoptosis in metastatic breast ductal carcinoma T-47D cell lines. Also, the protective effects of MNPs on hepatocytes are quite evident, and they can reduce the side effects of TMX.
{"title":"Improving Tamoxifen Performance in Inducing Apoptosis and Hepatoprotection by Loading on a Dual Nanomagnetic Targeting System","authors":"Yanfang Zhao, Wanbao Ding, Peixian Zhang, Lei Deng, Yi Long, Jiuqin Lu, Fereshteh Shiri, Mostafa Heidari Majd","doi":"10.2174/0118715206289666240423091244","DOIUrl":"https://doi.org/10.2174/0118715206289666240423091244","url":null,"abstract":"Background: Although tamoxifen (TMX) belongs to selective estrogen receptor modulators (SERMs) and selectively binds to estrogen receptors, it affects other estrogen-producing tissues due to passive diffusion and non-differentiation of normal and cancerous cells and leads to side effects. Methods: The problems expressed about tamoxifen (TMX) encouraged us to design a new drug delivery system based on magnetic nanoparticles (MNPs) to simultaneously target two receptors on cancer cells through folic acid (FA) and hyaluronic acid (HA) groups. The mediator of binding of two targeting agents to MNPs is a polymer linker, including dopamine, polyethylene glycol, and terminal amine (DPN). Results: Zeta potential, dynamic light scattering (DLS), and Field emission scanning electron microscopy (FESEM) methods confirmed that MNPs-DPN-HA-FA has a suitable size of ~105 nm and a surface charge of -41 mV, and therefore, it can be a suitable option for carrying TMX and increasing its solubility. The cytotoxic test showed that the highest concentration of MNPs-DPN-HA-FA-TMX decreased cell viability to about 11% after 72 h of exposure compared to the control. While the protective effect of modified MNPs on normal cells was evident, unlike tamoxifen, the survival rate of liver cells, even after 180 min of treatment, was not significantly different from the control group. The protective effect of MNPs was also confirmed by examining the amount of malondialdehyde, and no significant difference was observed in the amount of lipid peroxidation caused by modified MNPs compared to the control. Flow cytometry proved that TMX can induce apoptosis by targeting MNPs. Real-time PCR showed that the modified MNPs activated the intrinsic and extrinsic mitochondrial pathways of apoptosis, so the Bak1/Bclx ratio for MNPs-DPN-HA-FA-TMX and free TMX was 70.82 and 0.38, respectively. Also, the expression of the caspase-3 gene increased 430 times compared to the control. On the other hand, only TNF gene expression, which is responsible for metastasis in some tumors, was decreased by both free TMX and MNPs-DPN-HA-FA-TMX. Finally, molecular docking proved that MNPs-DPN-HA-FA-TMX could provide a very stable interaction with both CD44 and folate receptors, induce apoptosis in cancer cells, and reduce hepatotoxicity. Conclusion: All the results showed that MNPs-DPN-HA-FA-TMX can show good affinity to cancer cells using targeting agents and induce apoptosis in metastatic breast ductal carcinoma T-47D cell lines. Also, the protective effects of MNPs on hepatocytes are quite evident, and they can reduce the side effects of TMX.","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":"21 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Green synthesis offers a fast, simple, and economical method for producing metallic nanoparticles.The basis of this method is to obtain nanoparticles using natural materials, such as plants, fungi, and bacteria, instead of harmful and expensive chemical-reducing agents. In this study, CeO2NPs were produced using Alhagi maurorum extract, and their anticancer and antibacterial activities were evaluated. Method: Alhagi maurorum extract was prepared according to a previously described protocol, and CeO2NPs were synthesized from the salt of this extract. The resulting nanoparticles were characterized using Transmission electron microscopy (TEM), scanning electron microscope (SEM), and X-ray diffraction (XRD) techniques. The antibacterial and cytotoxic effects of the nanoparticles were measured by MIC, MBC, and MTT assays, respectively. The results were analyzed using one-way analysis of variance (ANOVA) using Prism software. Results: The MTT assay on breast cancer cell lines showed that the cytotoxic effect of CeO2NPs on cell lines was concentration-dependent. In addition, this nanoparticle was more effective against Gram-positive bacteria. Conclusion: These nanoparticles can be used as cancer drug delivery systems with specific targeting at low concentrations in addition to anticancer treatments. It can also have biological and medicinal applications, such as natural food preservation and wound dressing.
{"title":"Cerium Oxide Nanoparticles Synthesis Using Alhagi Maurorum Leaf Extract and Evaluation of Their Cytotoxic Effect on Breast Cancer Cell Lines and Antibacterial Effects","authors":"Sayedeh Azimeh Hosseini, Mehrdad Khatami, Amirkian Asadollahi, Hajar Yaghoobi","doi":"10.2174/0118715206296523240424072939","DOIUrl":"https://doi.org/10.2174/0118715206296523240424072939","url":null,"abstract":"Introduction: Green synthesis offers a fast, simple, and economical method for producing metallic nanoparticles.The basis of this method is to obtain nanoparticles using natural materials, such as plants, fungi, and bacteria, instead of harmful and expensive chemical-reducing agents. In this study, CeO2NPs were produced using Alhagi maurorum extract, and their anticancer and antibacterial activities were evaluated. Method: Alhagi maurorum extract was prepared according to a previously described protocol, and CeO2NPs were synthesized from the salt of this extract. The resulting nanoparticles were characterized using Transmission electron microscopy (TEM), scanning electron microscope (SEM), and X-ray diffraction (XRD) techniques. The antibacterial and cytotoxic effects of the nanoparticles were measured by MIC, MBC, and MTT assays, respectively. The results were analyzed using one-way analysis of variance (ANOVA) using Prism software. Results: The MTT assay on breast cancer cell lines showed that the cytotoxic effect of CeO2NPs on cell lines was concentration-dependent. In addition, this nanoparticle was more effective against Gram-positive bacteria. Conclusion: These nanoparticles can be used as cancer drug delivery systems with specific targeting at low concentrations in addition to anticancer treatments. It can also have biological and medicinal applications, such as natural food preservation and wound dressing.","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":"14 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: As a beneficial natural flavonoid, genistein has demonstrated a wide range of biological functions via regulating a number of targets and signaling pathways, such as anti-cancer, antioxidant, antibacterial, antiinflammatory, antifungal, antiviral, iron chelation, anti-obesity, anti-diabetes, and anti-hypertension. PubMed/Medline and Web of Science were searched using appropriate keywords until the end of December 2023. Despite its many potential benefits, genistein’s clinical application is limited by low hydrophilicity, poor solubility, and suboptimal bioavailability due to its structure. These challenges can be addressed through the conversion of genistein into glycosides. Glycosylation of active small molecules may enhance their solubility, stability, and biological activity. In recent years, extensive research has been conducted on the synthesis, properties, and anticancer activity of glycoconjugates. Previous reviews were devoted to discussing the biological activities of genistin, with a little summary of the biosynthesis and the structure-activity relationship for their anticancer activity of genistein glycoside derivatives. Therefore, we summarized recent advances in the biosynthesis of genistein glycosylation and discussed the antitumor activities of genistein glycoside derivatives in a structure-activity relationship, which may provide important information for further development of genistein derivatives.
:作为一种有益的天然类黄酮,染料木素通过调节多个靶点和信号通路,如抗癌、抗氧化、抗菌、抗炎、抗真菌、抗病毒、螯合铁、抗肥胖、抗糖尿病和抗高血压等,显示出广泛的生物学功能。在 2023 年 12 月底之前,我们使用适当的关键词对 PubMed/Medline 和 Web of Science 进行了检索。尽管染料木素具有许多潜在的益处,但由于其结构的原因,染料木素的临床应用受到亲水性低、溶解性差和生物利用度不理想的限制。这些难题可以通过将染料木素转化为糖苷来解决。活性小分子的糖基化可提高其溶解性、稳定性和生物活性。近年来,人们对糖类共轭物的合成、性质和抗癌活性进行了广泛的研究。以往的综述主要讨论了染料木素的生物活性,对染料木素苷衍生物的生物合成及其抗癌活性的结构-活性关系进行了少量总结。因此,我们总结了最近在染料木苷糖基化的生物合成方面取得的进展,并从结构-活性关系的角度讨论了染料木苷衍生物的抗肿瘤活性,这可能会为染料木苷衍生物的进一步开发提供重要信息。
{"title":"Biosynthesis and Anticancer Activity of Genistein Glycoside Derivatives","authors":"Xing Zheng, Jun Zhang, Shun Liu, Yingzi Yu, Qingying Peng, Yaling Peng, Xu Yao, Xingxing Peng, Jing Zhou","doi":"10.2174/0118715206299272240409043726","DOIUrl":"https://doi.org/10.2174/0118715206299272240409043726","url":null,"abstract":": As a beneficial natural flavonoid, genistein has demonstrated a wide range of biological functions via regulating a number of targets and signaling pathways, such as anti-cancer, antioxidant, antibacterial, antiinflammatory, antifungal, antiviral, iron chelation, anti-obesity, anti-diabetes, and anti-hypertension. PubMed/Medline and Web of Science were searched using appropriate keywords until the end of December 2023. Despite its many potential benefits, genistein’s clinical application is limited by low hydrophilicity, poor solubility, and suboptimal bioavailability due to its structure. These challenges can be addressed through the conversion of genistein into glycosides. Glycosylation of active small molecules may enhance their solubility, stability, and biological activity. In recent years, extensive research has been conducted on the synthesis, properties, and anticancer activity of glycoconjugates. Previous reviews were devoted to discussing the biological activities of genistin, with a little summary of the biosynthesis and the structure-activity relationship for their anticancer activity of genistein glycoside derivatives. Therefore, we summarized recent advances in the biosynthesis of genistein glycosylation and discussed the antitumor activities of genistein glycoside derivatives in a structure-activity relationship, which may provide important information for further development of genistein derivatives.","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":"22 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-17DOI: 10.2174/0118715206309421240402093335
Nurul Amalina Abd Aziz, Normah Awang, Nurul Farahana Kamaludin, Nur Najmi Mohamad Anuar, Asmah Hamid, Kok Meng Chan, Suhana Arshad
Background: Organotin(IV) complexes of dithiocarbamate are vital in medicinal chemistry, exhibiting potential in targeting cancer cells due to their unique properties that enhance targeted delivery. This study aimed to synthesize and characterize organotin(IV) N-ethyl-N-benzyldithiocarbamate complexes (ONBDCs) and evaluate their cytotoxicity against A549 cells, which are commonly used as a model for human lung cancer research. background: Organotin(IV) compounds exhibit potent cytotoxicity through two primary mechanisms: binding to DNA via external phosphate groups and disrupting internal phospholipid metabolism, similarly to the mechanism of action of cisplatin. Additionally, the distinct stereoelectronic properties of these compounds endow them with exceptional therapeutic potential. Method: The two ONBDC derivatives – ONBDC 1 (dimethyltin(IV) N-ethyl-N-benzyldithiocarbamate) and ONBDC 2 (triphenyltin(IV) N-ethyl-N-benzyldithiocarbamate) – were synthesized via the reaction of tin(IV) chloride with N-ethylbenzylamine in the presence of carbon disulfide. A range of analytical techniques, including elemental analysis, IR spectroscopy, NMR spectroscopy, UV-Vis spectrometry, TGA/DTA analysis, and X-ray crystallography, was conducted to characterize these compounds comprehensively. The cytotoxic effects of ONBDCs against A549 cells were evaluated using MTT assay. Results: Both compounds were synthesized and characterized successfully via elemental and spectroscopies analysis. MTT assay revealed that ONBDC 2 demonstrated remarkable cytotoxicity towards A549 cells, with an IC50 value of 0.52 μM. Additionally, ONBDC 2 displayed significantly higher cytotoxic activity against the A549 cell line when compared to the commercially available chemotherapeutic agent cisplatin (IC50: 32 μM). method: The compound was synthesized by using the in-situ method. Then, we used the elemental and spectroscopies analysis to characterize the compound. Subsequently, the cytotoxic potential of this compound is screened by using MTT assay. Conclusion: Thus, it was shown that ONBDC 2 could have important anticancer properties and should be further explored as a top contender for creating improved and specialized cancer treatments.
{"title":"The Development of Organotin(IV) N-Ethyl-N-Benzyldithiocarbamate Complexes: A Study on Their Synthesis, Characterization, and Cytocidal Effects on A549 Cell Line","authors":"Nurul Amalina Abd Aziz, Normah Awang, Nurul Farahana Kamaludin, Nur Najmi Mohamad Anuar, Asmah Hamid, Kok Meng Chan, Suhana Arshad","doi":"10.2174/0118715206309421240402093335","DOIUrl":"https://doi.org/10.2174/0118715206309421240402093335","url":null,"abstract":"Background: Organotin(IV) complexes of dithiocarbamate are vital in medicinal chemistry, exhibiting potential in targeting cancer cells due to their unique properties that enhance targeted delivery. This study aimed to synthesize and characterize organotin(IV) N-ethyl-N-benzyldithiocarbamate complexes (ONBDCs) and evaluate their cytotoxicity against A549 cells, which are commonly used as a model for human lung cancer research. background: Organotin(IV) compounds exhibit potent cytotoxicity through two primary mechanisms: binding to DNA via external phosphate groups and disrupting internal phospholipid metabolism, similarly to the mechanism of action of cisplatin. Additionally, the distinct stereoelectronic properties of these compounds endow them with exceptional therapeutic potential. Method: The two ONBDC derivatives – ONBDC 1 (dimethyltin(IV) N-ethyl-N-benzyldithiocarbamate) and ONBDC 2 (triphenyltin(IV) N-ethyl-N-benzyldithiocarbamate) – were synthesized via the reaction of tin(IV) chloride with N-ethylbenzylamine in the presence of carbon disulfide. A range of analytical techniques, including elemental analysis, IR spectroscopy, NMR spectroscopy, UV-Vis spectrometry, TGA/DTA analysis, and X-ray crystallography, was conducted to characterize these compounds comprehensively. The cytotoxic effects of ONBDCs against A549 cells were evaluated using MTT assay. Results: Both compounds were synthesized and characterized successfully via elemental and spectroscopies analysis. MTT assay revealed that ONBDC 2 demonstrated remarkable cytotoxicity towards A549 cells, with an IC50 value of 0.52 μM. Additionally, ONBDC 2 displayed significantly higher cytotoxic activity against the A549 cell line when compared to the commercially available chemotherapeutic agent cisplatin (IC50: 32 μM). method: The compound was synthesized by using the in-situ method. Then, we used the elemental and spectroscopies analysis to characterize the compound. Subsequently, the cytotoxic potential of this compound is screened by using MTT assay. Conclusion: Thus, it was shown that ONBDC 2 could have important anticancer properties and should be further explored as a top contender for creating improved and specialized cancer treatments.","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":"30 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-17DOI: 10.2174/0118715206287870240408031843
Lin Tan, Juan C. Solis-Sainz
Background: Monochasma savatieri, is a rare and endangered plant used to treat cancer in Chinese traditional medicine. Objective: To evaluate the anti-cancer activity of M. savatieri aqueous extract by determining its cytotoxicity, anti-migratory, and anti-adhesion effects on breast cancer cells. objective: To evaluate the anti-cancer activity of M. savatieri aqueous extract by determining its cytotoxicity, anti-migratory and anti-adhesion effects on breast cancer cells. Methods: Cell viability, migration, adhesion, circularity, and cell cycle were evaluated by crystal violet (CV) staining, wound-healing, and transwell assays and flow cytometry in MCF7 and MDA-MB-231 cells. Caveolin-1, snail, vimentin and activated Erk and Akt expression were determined by western blot in MDA-MB-231 cells. Immunofluorescent assays confirmed caveolin-1 expression in MDA-MB-231 cells. method: Cell viability, migration, adhesion, circularity, and cell cycle were evaluated by crystal violet staining, wound-healing and transwell assays and flow cytometry in MCF7 and MDA-MB-231 cells. Caveolin-1, snail, vimentin and activated Erk and Akt expression were determined by western blot in MDA-MB-231 cells. Caveolin-1 expression in MDA-MB-231 cells was confirmed by immunofluorescent assays. Results: Survival and cell cycle of MCF7 and MDA-MB-231 cells were not modified by doses up to 500 μg/mL of the extract. The extract inhibited cell migration and adhesion of MDA-MB-231 cells. When cells were exposed to the extract, there was a slight decrease in protein expression of factors related to epithelial-to-mesenchymal transition (snail and vimentin) and a strong decrease in the expression of the oncogenic membrane protein caveolin- 1. Furthermore, the levels of phosphorylated Erk and Akt were also decreased. The content of acteoside, a phenylpropanoid glycoside with reported anti-cancer activity present in M. savatieri, was almost 5 times as much as isoacteoside. Conclusion: M. savatieri possesses anti-cancer activity without exerting cytotoxicity on breast cancer cells. The extract exhibited anti-migratory and anti-adhesion effects on breast cancer cells by regulating Erk and Akt signaling pathways and the expression of caveolin-1. In addition, acteoside present in M. savatieri could be responsible for the observed effects. conclusion: M. savatieri possesses anti-cancer activity without exerting cytotoxicity on breast cancer cells. The extract exerted anti-migratory and anti-adhesion effects on breast cancer cells by regulating Erk and Akt signaling pathways and the expression of caveolin-1. In addition, acteoside present in M. savatieri could be responsible for the observed effects.
{"title":"Monochasma Savatieri Aqueous Extract inhibits Human Breast Cancer Cell Line Migration and Adhesion Without Generating Toxicity","authors":"Lin Tan, Juan C. Solis-Sainz","doi":"10.2174/0118715206287870240408031843","DOIUrl":"https://doi.org/10.2174/0118715206287870240408031843","url":null,"abstract":"Background: Monochasma savatieri, is a rare and endangered plant used to treat cancer in Chinese traditional medicine. Objective: To evaluate the anti-cancer activity of M. savatieri aqueous extract by determining its cytotoxicity, anti-migratory, and anti-adhesion effects on breast cancer cells. objective: To evaluate the anti-cancer activity of M. savatieri aqueous extract by determining its cytotoxicity, anti-migratory and anti-adhesion effects on breast cancer cells. Methods: Cell viability, migration, adhesion, circularity, and cell cycle were evaluated by crystal violet (CV) staining, wound-healing, and transwell assays and flow cytometry in MCF7 and MDA-MB-231 cells. Caveolin-1, snail, vimentin and activated Erk and Akt expression were determined by western blot in MDA-MB-231 cells. Immunofluorescent assays confirmed caveolin-1 expression in MDA-MB-231 cells. method: Cell viability, migration, adhesion, circularity, and cell cycle were evaluated by crystal violet staining, wound-healing and transwell assays and flow cytometry in MCF7 and MDA-MB-231 cells. Caveolin-1, snail, vimentin and activated Erk and Akt expression were determined by western blot in MDA-MB-231 cells. Caveolin-1 expression in MDA-MB-231 cells was confirmed by immunofluorescent assays. Results: Survival and cell cycle of MCF7 and MDA-MB-231 cells were not modified by doses up to 500 μg/mL of the extract. The extract inhibited cell migration and adhesion of MDA-MB-231 cells. When cells were exposed to the extract, there was a slight decrease in protein expression of factors related to epithelial-to-mesenchymal transition (snail and vimentin) and a strong decrease in the expression of the oncogenic membrane protein caveolin- 1. Furthermore, the levels of phosphorylated Erk and Akt were also decreased. The content of acteoside, a phenylpropanoid glycoside with reported anti-cancer activity present in M. savatieri, was almost 5 times as much as isoacteoside. Conclusion: M. savatieri possesses anti-cancer activity without exerting cytotoxicity on breast cancer cells. The extract exhibited anti-migratory and anti-adhesion effects on breast cancer cells by regulating Erk and Akt signaling pathways and the expression of caveolin-1. In addition, acteoside present in M. savatieri could be responsible for the observed effects. conclusion: M. savatieri possesses anti-cancer activity without exerting cytotoxicity on breast cancer cells. The extract exerted anti-migratory and anti-adhesion effects on breast cancer cells by regulating Erk and Akt signaling pathways and the expression of caveolin-1. In addition, acteoside present in M. savatieri could be responsible for the observed effects.","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":"161 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.2174/0118715206269038231203151111
Soha Gomaa, Mohamed Nassef, Randa El-Naggar, Ahmed Massoud, Mona El-Kholy
Background:: Due to its systemic toxicity, traditional chemotherapy of tumors is being taken into consideration. Herbal therapy, containing phytochemical polyphenol derivatives such as Curcumin (Cur), Ginger (Gin), Cloves (Clov) and Amygdaline (Amyg), is one of the numerous complementary and alternative approaches as an anti-cancer therapy and holds great promise for cancer chemo-prevention with fewer side effects. Aim:: The current study was designated to assess anti-tumoral immunity and anti-cancer and chemo-preventive effectiveness of herbal extracts of Cur, Ginger, Clov and Amyg in Ehrlich Ascites Carcinoma (EAC)-challenging mice. Methods: Chemo-preventive efficacy of herbal extracts of Cur, Gin, Clov and Amyg were analyzed in vivo by examination of the apoptosis rate of EAC tumor cells by flow cytometry. The total numbers of EAC cells, splenocytes counts and leucocytes count with their differentials relative % in peripheral blood (PB) of EACchallenging mice were investigated. Results:: EAC-challenging mice treated with herbal extracts of Cur, Gin, Clov and Amyg showed a marked decline in EAC tumor cell count and a noticeable increase in apoptosis rate of EAC tumor cells, a remarkable decrease in serum level of cancer antigen 125 (CA-125) with an obvious increase in the number of splenocytes comparing to that in EAC-challenging mice treated with PBS alone. Moreover, the data indicated an insignificant change in the total leucocytes count and their differentials relative % of eosinophil, neutrophils, monocytes and lymphocytes in EAC-challenging mice treated with Cur and Amyg, but these parameters were markedly increased in EAC-challenging mice injected with Gin and Clov compared to that in EAC-challenging mice treated with PBS alone. Conclusion:: To conclude, the herbal extracts of Cur, Gin, Clov and Amyg may have anti-tumoral immunity and anti-cancer potency and potential to reduce the resistance to cancer conventional chemotherapy and exert cancer chemo-protective approaches with low adverse effects. Further research is necessary to determine the regimen's toxicity on various tissues and organs and to connect the diagnostic and therapeutic approaches used in the regimen's biomedical use.
{"title":"Anti-tumoral Immunity and Chemo-preventive Effectiveness of Herbal Extracts of Curcumin, Ginger, Clove and Amygdaline in Ehrlich Ascites Carcinoma-Challenging Mice","authors":"Soha Gomaa, Mohamed Nassef, Randa El-Naggar, Ahmed Massoud, Mona El-Kholy","doi":"10.2174/0118715206269038231203151111","DOIUrl":"https://doi.org/10.2174/0118715206269038231203151111","url":null,"abstract":"Background:: Due to its systemic toxicity, traditional chemotherapy of tumors is being taken into consideration. Herbal therapy, containing phytochemical polyphenol derivatives such as Curcumin (Cur), Ginger (Gin), Cloves (Clov) and Amygdaline (Amyg), is one of the numerous complementary and alternative approaches as an anti-cancer therapy and holds great promise for cancer chemo-prevention with fewer side effects. Aim:: The current study was designated to assess anti-tumoral immunity and anti-cancer and chemo-preventive effectiveness of herbal extracts of Cur, Ginger, Clov and Amyg in Ehrlich Ascites Carcinoma (EAC)-challenging mice. Methods: Chemo-preventive efficacy of herbal extracts of Cur, Gin, Clov and Amyg were analyzed in vivo by examination of the apoptosis rate of EAC tumor cells by flow cytometry. The total numbers of EAC cells, splenocytes counts and leucocytes count with their differentials relative % in peripheral blood (PB) of EACchallenging mice were investigated. Results:: EAC-challenging mice treated with herbal extracts of Cur, Gin, Clov and Amyg showed a marked decline in EAC tumor cell count and a noticeable increase in apoptosis rate of EAC tumor cells, a remarkable decrease in serum level of cancer antigen 125 (CA-125) with an obvious increase in the number of splenocytes comparing to that in EAC-challenging mice treated with PBS alone. Moreover, the data indicated an insignificant change in the total leucocytes count and their differentials relative % of eosinophil, neutrophils, monocytes and lymphocytes in EAC-challenging mice treated with Cur and Amyg, but these parameters were markedly increased in EAC-challenging mice injected with Gin and Clov compared to that in EAC-challenging mice treated with PBS alone. Conclusion:: To conclude, the herbal extracts of Cur, Gin, Clov and Amyg may have anti-tumoral immunity and anti-cancer potency and potential to reduce the resistance to cancer conventional chemotherapy and exert cancer chemo-protective approaches with low adverse effects. Further research is necessary to determine the regimen's toxicity on various tissues and organs and to connect the diagnostic and therapeutic approaches used in the regimen's biomedical use.","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":"42 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.2174/0118715206294031240404071838
ShuangYi Lei, ShanShan Tian, SongMei Lu, Zhou Qing, JianLin Long, LuChun Li, Dan Yang
Background: Primary Pulmonary Lymphoepithelioma-like Carcinoma (PPLELC) is a rare form of cancer for which no standard treatment has been established to date. Patients with advanced-stage PPLELC generally have a poor prognosis with overall survival of 22.7 months. Case Presentation: Here, we report a case of advanced primary pulmonary lymphoepithelioma-like carcinoma. Initially, the patient underwent a first-line (GP) and a second-line (DP) of chemotherapy, which provided temporary relief but resulted in varying degrees of myelosuppression. When the disease progressed again, we administered a third-line treatment consisting of camrelizumab combined with anlotinib. Result: This resulted in a progression-free survival of over 26 months without significant toxic side effects. Conclusion: Our findings suggest that combining camrelizumab and anlotinib could lead to a long progressionfree survival in patients with advanced PPLELC.
{"title":"Primary Pulmonary Lymphoepithelioma-like Carcinoma: A Case Report Utilizing Camrelizumab and Anlotinib for Prolonged Survival","authors":"ShuangYi Lei, ShanShan Tian, SongMei Lu, Zhou Qing, JianLin Long, LuChun Li, Dan Yang","doi":"10.2174/0118715206294031240404071838","DOIUrl":"https://doi.org/10.2174/0118715206294031240404071838","url":null,"abstract":"Background: Primary Pulmonary Lymphoepithelioma-like Carcinoma (PPLELC) is a rare form of cancer for which no standard treatment has been established to date. Patients with advanced-stage PPLELC generally have a poor prognosis with overall survival of 22.7 months. Case Presentation: Here, we report a case of advanced primary pulmonary lymphoepithelioma-like carcinoma. Initially, the patient underwent a first-line (GP) and a second-line (DP) of chemotherapy, which provided temporary relief but resulted in varying degrees of myelosuppression. When the disease progressed again, we administered a third-line treatment consisting of camrelizumab combined with anlotinib. Result: This resulted in a progression-free survival of over 26 months without significant toxic side effects. Conclusion: Our findings suggest that combining camrelizumab and anlotinib could lead to a long progressionfree survival in patients with advanced PPLELC.","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140565943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}