Background: It is noteworthy that a wide array of plants and nutraceuticals are effectively utilized in the treatment of various cancers, demonstrating potent effects on different cancer targets with fewer side effects. Notably, estrogen alpha has been identified as a crucial factor in breast cancer cell proliferation. Agents that can antagonize its action hold promise as potential drug leads for the treatment of breast cancer. Objective: This study aims to discover and identify the potential inhibitors against the most influential ERα receptor by the computational approach of 134 phytochemicals from 17 medicinal plants by using in silico docking studies. Methods: The molecular docking was performedby a genetic algorithm using the Auto Dock Vina program, and the validation of docking was also performed by using Molecular Dynamic (MD) simulation by the Desmond tool of Schrödinger molecular modeling. Drug-likeness properties and toxicity studies were conducted using SWISS PRO. Results: The top ten highest binding energy phytochemicals ginicidin (-10.8 kcal/mol), lemairone (-10.5 kcal/mol), ixoratannin (-10.0 kcal/mol), hydnocarpine (-9.8 kcal/mol), arabelline (-9.8 kcal/mol), acutilobine E (-9.8 kcal/mol), chaparinone (-8.9 kcal/mol), plumieride coumerate (-8.8 kcal/mol), acutilobine C (-8.7 kcal/mol), and mezerein (-8.7 kcal/mol) were taken for drug-likeness test and ADMET profile prediction with the help of web-based server SWISS ADME and protoxII. Docking's study dictated that ten phytochemical constituents showed greater binding interactions than standard tamoxifen (-6.6 kcal/mol) towards the target protein ERα. MSD study was achieved for the most active 4 phytoconstituents, and the stability of the ligand-protein complex was confirmed and showed that all the four compounds possess comparatively stable ligand-protein complexes with ERα target as compared to the tamoxifen-ERα complex. Conclusion: Among the top ten phytochemicals, ginicidin (glycoside) formed a more stable complex and had greater binding affinity than standard tamoxifen with better safety profiles. Hence, this compound can be further studied for lead optimization and drug development for the treatment of breast cancer.
{"title":"In Silico Studies of Phytoconstituents to Identify Potential Inhibitors for ERα Protein of Breast Cancer","authors":"Veerachamy Alagarsamy, Mohaideen Thasthagir Sulthana, Bandi Narendhar, Viswas Raja Solomon, Periyasamy Parthiban, Aithamraju Satishchandra, Lalkote Aruna Jothi, Sankaranarayanan Murugesan","doi":"10.2174/0115734064301748240821081206","DOIUrl":"https://doi.org/10.2174/0115734064301748240821081206","url":null,"abstract":"Background: It is noteworthy that a wide array of plants and nutraceuticals are effectively utilized in the treatment of various cancers, demonstrating potent effects on different cancer targets with fewer side effects. Notably, estrogen alpha has been identified as a crucial factor in breast cancer cell proliferation. Agents that can antagonize its action hold promise as potential drug leads for the treatment of breast cancer. Objective: This study aims to discover and identify the potential inhibitors against the most influential ERα receptor by the computational approach of 134 phytochemicals from 17 medicinal plants by using in silico docking studies. Methods: The molecular docking was performedby a genetic algorithm using the Auto Dock Vina program, and the validation of docking was also performed by using Molecular Dynamic (MD) simulation by the Desmond tool of Schrödinger molecular modeling. Drug-likeness properties and toxicity studies were conducted using SWISS PRO. Results: The top ten highest binding energy phytochemicals ginicidin (-10.8 kcal/mol), lemairone (-10.5 kcal/mol), ixoratannin (-10.0 kcal/mol), hydnocarpine (-9.8 kcal/mol), arabelline (-9.8 kcal/mol), acutilobine E (-9.8 kcal/mol), chaparinone (-8.9 kcal/mol), plumieride coumerate (-8.8 kcal/mol), acutilobine C (-8.7 kcal/mol), and mezerein (-8.7 kcal/mol) were taken for drug-likeness test and ADMET profile prediction with the help of web-based server SWISS ADME and protoxII. Docking's study dictated that ten phytochemical constituents showed greater binding interactions than standard tamoxifen (-6.6 kcal/mol) towards the target protein ERα. MSD study was achieved for the most active 4 phytoconstituents, and the stability of the ligand-protein complex was confirmed and showed that all the four compounds possess comparatively stable ligand-protein complexes with ERα target as compared to the tamoxifen-ERα complex. Conclusion: Among the top ten phytochemicals, ginicidin (glycoside) formed a more stable complex and had greater binding affinity than standard tamoxifen with better safety profiles. Hence, this compound can be further studied for lead optimization and drug development for the treatment of breast cancer.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227266","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 : 2024-09-05DOI: 10.2174/0115734064308484240820080153
Farid M. Sroor, Eman A. Younis, Hanan F. Aly
Background: Alternative and complementary applications of newly synthesized chemicals have enhanced the prospect of finding curative treatments for liver hepatocarcinogenesis and pancreatic cancer. Methods: The current study investigated the curative effect of the newly synthesized drug 4- methyl-N-((4-(trifluoromethoxy) phenyl) carbamoyl) benzenesulfonamide (3) against diethyl nitrosamine (DEN) (50 mg/kg) and carbon tetrachloride (CCl4) (2 mg/kg)-induced hepatocellular carcinoma (HCC) and pancreatic cancer in male rats using doxorubicin as a reference drug. Results: The findings demonstrated that the DEN/CCl4 treatment produced oxidative stress, as evidenced by an increase in MDA and a reduction in GSH levels. A temporary decline in antioxidant and total antioxidant capacity (TAC) was detected. An increase in the levels of TNF-α and other inflammatory markers, interleukin-6 (IL-6) and B-cell lymphoma 2 (Bcl-2), was found. Our findings showed that the liver and pancreas had significantly higher levels of hepatocellular carcinoma biomarkers, namely α-fetoprotein and α-L-Fucosidase (α-FU). Changes in the biomarkers of hepatic function were also seen, with elevated levels of γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), and transaminases (AST, ALT). Our findings were supported by immunohistochemical and pathological examinations, which revealed considerable improvement in liver and pancreatic tissues after treatment with medication 3 when compared to normal healthy rats. Conclusion: To summarize, the new synthetic medication 3 could be an effective chemotherapeutic method for treating DEN and CCl4-induced HCC and pancreatic cancer.
{"title":"A Preclinical Study on 4-Methyl-N-((4-(trifluoromethoxy)phenyl) carbamoyl)-benzenesulfonamide as a Potent Chemotherapeutic Agent against Liver and Pancreatic Carcinogenesis in Rats: Immunohistochemical and Histopathological Studies","authors":"Farid M. Sroor, Eman A. Younis, Hanan F. Aly","doi":"10.2174/0115734064308484240820080153","DOIUrl":"https://doi.org/10.2174/0115734064308484240820080153","url":null,"abstract":"Background: Alternative and complementary applications of newly synthesized chemicals have enhanced the prospect of finding curative treatments for liver hepatocarcinogenesis and pancreatic cancer. Methods: The current study investigated the curative effect of the newly synthesized drug 4- methyl-N-((4-(trifluoromethoxy) phenyl) carbamoyl) benzenesulfonamide (3) against diethyl nitrosamine (DEN) (50 mg/kg) and carbon tetrachloride (CCl4) (2 mg/kg)-induced hepatocellular carcinoma (HCC) and pancreatic cancer in male rats using doxorubicin as a reference drug. Results: The findings demonstrated that the DEN/CCl4 treatment produced oxidative stress, as evidenced by an increase in MDA and a reduction in GSH levels. A temporary decline in antioxidant and total antioxidant capacity (TAC) was detected. An increase in the levels of TNF-α and other inflammatory markers, interleukin-6 (IL-6) and B-cell lymphoma 2 (Bcl-2), was found. Our findings showed that the liver and pancreas had significantly higher levels of hepatocellular carcinoma biomarkers, namely α-fetoprotein and α-L-Fucosidase (α-FU). Changes in the biomarkers of hepatic function were also seen, with elevated levels of γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), and transaminases (AST, ALT). Our findings were supported by immunohistochemical and pathological examinations, which revealed considerable improvement in liver and pancreatic tissues after treatment with medication 3 when compared to normal healthy rats. Conclusion: To summarize, the new synthetic medication 3 could be an effective chemotherapeutic method for treating DEN and CCl4-induced HCC and pancreatic cancer.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219124","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}
Background: Oxadiazole derivatives have shown significant potential as anti-cancer agents with low μM potencies. Some examples of drugs in this class include Raltegravir, Zibotentan, Setileuton (MK-0633), Nesapidil, Furamizole, and Tidazosin. The presence of the oxadiazole nucleus in Raltegravir exemplifies its importance in drug development, showcasing how specific structural motifs like oxadiazole can be strategically incorporated into molecules to achieve desired therapeutic effects. A large number of researchers across the globe have already developed and reported many oxadiazoles as potential anti-cancer medicines. Objective: Therefore, we tried to discuss the anti-cancer potentials of oxadiazole derivatives reported between 2019 and 2023. The design strategies, structure-activity relationship (SAR), and protein- inhibitor interactions of potential compounds on different targets have to be identified to help the medicinal chemists design new drug-likeness oxadiazole molecules for anti-cancer therapy. Similarly, the ADMET profiles of potential oxadiazoles using the in silico SWISSADME tool have to be studied. Results: We have highlighted the recently reported most potent oxadiazole derivatives as well as their hybrid compounds. The SAR study revealed that oxadiazole-linked pyridine, indazole, thiadiazine, quinoxaline, thiazolidine, indeno-pyrazole, thiophene, piperidine, benzimidazole, triazole, and sulphonamide showcased promising anti-cancer action. The chemico-biological interactions of potential oxadiazole compounds suggest good interactions with different amino acid residues that make them possible candidates for developing novel and effective anti-cancer therapies. Similarly, the in silico ADMET report suggested favourable physicochemical, pharmacokinetic, and druglikeness properties of potential oxadiazole compounds. Conclusion: Overall, these results will prove to be a helpful and vital tool for medicinal chemists investigating and working with oxadiazoles for anti-cancer action.
{"title":"Unveiling the Anti-cancer Potential of Oxadiazole Derivatives: A Comprehensive Exploration of Structure-Activity Relationships and Chemico-Biological Insights","authors":"Sai Satyaprakash Mishra, Ajeya Samanta, Abhik Paul, Avik Maji, Tapan Kumar Maity","doi":"10.2174/0115734064329573240823113924","DOIUrl":"https://doi.org/10.2174/0115734064329573240823113924","url":null,"abstract":"Background: Oxadiazole derivatives have shown significant potential as anti-cancer agents with low μM potencies. Some examples of drugs in this class include Raltegravir, Zibotentan, Setileuton (MK-0633), Nesapidil, Furamizole, and Tidazosin. The presence of the oxadiazole nucleus in Raltegravir exemplifies its importance in drug development, showcasing how specific structural motifs like oxadiazole can be strategically incorporated into molecules to achieve desired therapeutic effects. A large number of researchers across the globe have already developed and reported many oxadiazoles as potential anti-cancer medicines. Objective: Therefore, we tried to discuss the anti-cancer potentials of oxadiazole derivatives reported between 2019 and 2023. The design strategies, structure-activity relationship (SAR), and protein- inhibitor interactions of potential compounds on different targets have to be identified to help the medicinal chemists design new drug-likeness oxadiazole molecules for anti-cancer therapy. Similarly, the ADMET profiles of potential oxadiazoles using the in silico SWISSADME tool have to be studied. Results: We have highlighted the recently reported most potent oxadiazole derivatives as well as their hybrid compounds. The SAR study revealed that oxadiazole-linked pyridine, indazole, thiadiazine, quinoxaline, thiazolidine, indeno-pyrazole, thiophene, piperidine, benzimidazole, triazole, and sulphonamide showcased promising anti-cancer action. The chemico-biological interactions of potential oxadiazole compounds suggest good interactions with different amino acid residues that make them possible candidates for developing novel and effective anti-cancer therapies. Similarly, the in silico ADMET report suggested favourable physicochemical, pharmacokinetic, and druglikeness properties of potential oxadiazole compounds. Conclusion: Overall, these results will prove to be a helpful and vital tool for medicinal chemists investigating and working with oxadiazoles for anti-cancer action.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219126","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 : 2024-09-02DOI: 10.2174/0115734064328915240827062052
Neetu Agrawal, Deepika Goyal, Shilpi Pathak
Thiazine, a six-membered heterocycle containing nitrogen and sulfur atoms, is of paramount importance due to its diverse biological functions and broad therapeutic effects. The pharmacological attributes of 1,3-thiazine span a wide range of activities, including antileukemic, antimycobacterial, anti-inflammatory, sedative, hypnotic, anti-influenza, antituberculosis, melanogenesis inhibition, BACE1 inhibition (with anti-Alzheimer's potential), growth promotion, neuroprotective, and anticonvulsant properties. Consequently, novel synthetic methodologies and the design of new 1,3-thiazine derivatives are significantly influenced by recent research findings. This comprehensive review explores both in vivo and in vitro preclinical studies on the biomedical and therapeutic applications of 1,3-thiazine, highlighting its extensive medical relevance. It is anticipated that derivatization strategies for 1,3-thiazine will open new avenues for the development of innovative biological agents. This review aims to engage researchers, stimulating the creation of promising new treatments and preventive measures for various diseases.
{"title":"Exploring the Diverse Therapeutic Applications of 1, 3-Thiazine: A Comprehensive Review","authors":"Neetu Agrawal, Deepika Goyal, Shilpi Pathak","doi":"10.2174/0115734064328915240827062052","DOIUrl":"https://doi.org/10.2174/0115734064328915240827062052","url":null,"abstract":"Thiazine, a six-membered heterocycle containing nitrogen and sulfur atoms, is of paramount importance due to its diverse biological functions and broad therapeutic effects. The pharmacological attributes of 1,3-thiazine span a wide range of activities, including antileukemic, antimycobacterial, anti-inflammatory, sedative, hypnotic, anti-influenza, antituberculosis, melanogenesis inhibition, BACE1 inhibition (with anti-Alzheimer's potential), growth promotion, neuroprotective, and anticonvulsant properties. Consequently, novel synthetic methodologies and the design of new 1,3-thiazine derivatives are significantly influenced by recent research findings. This comprehensive review explores both in vivo and in vitro preclinical studies on the biomedical and therapeutic applications of 1,3-thiazine, highlighting its extensive medical relevance. It is anticipated that derivatization strategies for 1,3-thiazine will open new avenues for the development of innovative biological agents. This review aims to engage researchers, stimulating the creation of promising new treatments and preventive measures for various diseases.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219125","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 : 2024-09-02DOI: 10.2174/0115734064317811240815184525
Tanzeel Ur Rehman, Yaser Abdulaziz Alnaam, Misbah Zahid, Jari S. Algethami
Aim: Due to interdisciplinary research, many innovative concepts have been merged that seemed to be impractical. Recently, medicinal organometallic chemistry has made remarkable progress, but the latency of these compounds has not been fully exploited. This systematic review has examined the published literature on anticancer organometallic chemistry across countries, science fields, and organizations involved in organometallics research for cancer. Method: The study data related to anticancer organometallics were searched from Scopus between 2085 and 2022. Biblioshiny and VOS Viewers were used to analyze and visualize patterns in scientific literature derived from Scopus. Results: Publications on organometallic compounds have been found to contribute to, on average, 1.02% per year, accounting for 94.3% of the total scholarly work published in the last two decades since 2003. However, research productivity has been found to be steadily improved, with 81.5% of all publications produced between 2011 and 2022. The countries possessing the highest published work have been found to be China, the UK, and Germany. The leading institutions, the University of Warwick, United Kingdom, and the University of Auckland, New Zealand, have topped the list of organizations with the most publications. Although the use of medicinal organometallics for cancer has become widespread over the last two decennaries, there has been a notable influx of groundbreaking scientific publications in recent years. Conclusion: The findings of this study may enable researchers to envision potential future scenarios for scientific collaborations involving the utilization of organometallics in the treatment of cancer. This study may provide aspiring and current researchers with the necessary tools and knowledge to effectively pursue their research endeavors for scientific collaborations investigating the use of anticancer organometallics in the medicinal field. The areas, such as ruthenium with reactive oxygen species and angiogenesis, represent opportunities for future investigation and innovation.
{"title":"Mapping the Landscape of Global Anticancer Organometallics Research: A Systematic Review","authors":"Tanzeel Ur Rehman, Yaser Abdulaziz Alnaam, Misbah Zahid, Jari S. Algethami","doi":"10.2174/0115734064317811240815184525","DOIUrl":"https://doi.org/10.2174/0115734064317811240815184525","url":null,"abstract":"Aim: Due to interdisciplinary research, many innovative concepts have been merged that seemed to be impractical. Recently, medicinal organometallic chemistry has made remarkable progress, but the latency of these compounds has not been fully exploited. This systematic review has examined the published literature on anticancer organometallic chemistry across countries, science fields, and organizations involved in organometallics research for cancer. Method: The study data related to anticancer organometallics were searched from Scopus between 2085 and 2022. Biblioshiny and VOS Viewers were used to analyze and visualize patterns in scientific literature derived from Scopus. Results: Publications on organometallic compounds have been found to contribute to, on average, 1.02% per year, accounting for 94.3% of the total scholarly work published in the last two decades since 2003. However, research productivity has been found to be steadily improved, with 81.5% of all publications produced between 2011 and 2022. The countries possessing the highest published work have been found to be China, the UK, and Germany. The leading institutions, the University of Warwick, United Kingdom, and the University of Auckland, New Zealand, have topped the list of organizations with the most publications. Although the use of medicinal organometallics for cancer has become widespread over the last two decennaries, there has been a notable influx of groundbreaking scientific publications in recent years. Conclusion: The findings of this study may enable researchers to envision potential future scenarios for scientific collaborations involving the utilization of organometallics in the treatment of cancer. This study may provide aspiring and current researchers with the necessary tools and knowledge to effectively pursue their research endeavors for scientific collaborations investigating the use of anticancer organometallics in the medicinal field. The areas, such as ruthenium with reactive oxygen species and angiogenesis, represent opportunities for future investigation and innovation.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219129","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 : 2024-09-02DOI: 10.2174/0115734064327558240826050650
Irena Kostova
: Although platinum and ruthenium complexes have been clinically recognized to be the most efficient metal-based anticancer candidates, applied in a wide range of cancer cell lines, their serious toxic effects and drug resistance require the necessity for new metal antitumor complexes. There is excessive interest in the design of new Pt-group metal complexes, including osmium and rhodium, which have revealed great chemotherapeutic potential. They have demonstrated modes of action that differ from those of the most broadly-used in clinical practice platinum- and rutheniumbased compounds. Os and Rh complexes are equipotent to their platinum and ruthenium analogues. Many Os- and Rh-based complexes with strong antitumor activity and low toxic effects have been developed and recognized for their antineoplastic activity in the last few years. Some of them have exposed different action profiles from the conventional anticancer metal complexes. That is why they might serve as a possible alternative that deserves more investigation, though limited studies on their biological effects have been reported, which is in contrast with the classical isoelectronic Pt and Ru complex compounds. Studies of Os and Rh complexes are currently attracting scientific attention. Recent developments of this interesting class of novel chemotherapeutic agents have been reviewed.
{"title":"Recent Advances in Anticancer Research of Osmium and Rhodium Complexes","authors":"Irena Kostova","doi":"10.2174/0115734064327558240826050650","DOIUrl":"https://doi.org/10.2174/0115734064327558240826050650","url":null,"abstract":": Although platinum and ruthenium complexes have been clinically recognized to be the most efficient metal-based anticancer candidates, applied in a wide range of cancer cell lines, their serious toxic effects and drug resistance require the necessity for new metal antitumor complexes. There is excessive interest in the design of new Pt-group metal complexes, including osmium and rhodium, which have revealed great chemotherapeutic potential. They have demonstrated modes of action that differ from those of the most broadly-used in clinical practice platinum- and rutheniumbased compounds. Os and Rh complexes are equipotent to their platinum and ruthenium analogues. Many Os- and Rh-based complexes with strong antitumor activity and low toxic effects have been developed and recognized for their antineoplastic activity in the last few years. Some of them have exposed different action profiles from the conventional anticancer metal complexes. That is why they might serve as a possible alternative that deserves more investigation, though limited studies on their biological effects have been reported, which is in contrast with the classical isoelectronic Pt and Ru complex compounds. Studies of Os and Rh complexes are currently attracting scientific attention. Recent developments of this interesting class of novel chemotherapeutic agents have been reviewed.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219127","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 : 2024-08-29DOI: 10.2174/0115734064314933240812120123
Sony A.S., Xavier Suresh
Background: Flavonoids express a wide range of medicinal properties, our study presented results on the anticancer activity of selected compounds using in silico studies. Objective: In this article, in silico studies were carried out to find promising anticancer lead among selected flavonoid compounds. Methods: Here, we carried out molecular docking and MD simulation for anticancer screening of flavonoid derivatives against CDK2 and CDK9 proteins. Results: Among the compounds under investigation, Flavone and Recoflavone had the lowest binding energy against CDK2/CDK9 targets using docking studies and MD simulations. Conclusion: We can conclude that Flavone and Recoflavone are promising anticancer lead compounds in the development of new anticancer drugs.
{"title":"Docking and Molecular Dynamics Studies on Anticancer Activities of Flavonoids as Inhibitors of CDK2 and CDK9","authors":"Sony A.S., Xavier Suresh","doi":"10.2174/0115734064314933240812120123","DOIUrl":"https://doi.org/10.2174/0115734064314933240812120123","url":null,"abstract":"Background: Flavonoids express a wide range of medicinal properties, our study presented results on the anticancer activity of selected compounds using in silico studies. Objective: In this article, in silico studies were carried out to find promising anticancer lead among selected flavonoid compounds. Methods: Here, we carried out molecular docking and MD simulation for anticancer screening of flavonoid derivatives against CDK2 and CDK9 proteins. Results: Among the compounds under investigation, Flavone and Recoflavone had the lowest binding energy against CDK2/CDK9 targets using docking studies and MD simulations. Conclusion: We can conclude that Flavone and Recoflavone are promising anticancer lead compounds in the development of new anticancer drugs.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219128","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 : 2024-08-28DOI: 10.2174/0115734064315601240628115330
Md. Abdullah Al Mashud, Ramprosad Devnath, Masuma Anzuman, Mahbuba Iasmin Sumona, Md. Shamim Hossain, Ajoy Kumer, Md. Enamul Kabir Talukder, Md. Mashiar Rahman, Raihan Rahman Imon, Shopnil Akash, Abdelfattah El Moussaoui, Ahmad Mohammad Salamatullah, Mohammed Bourhia
Background: Head and neck cancer (HNC) is on the rise worldwide, endangering lives and straining healthcare systems in both developing and developed nations. Despite the availability of a number of therapy options, the success rate for treating and controlling head and neck cancer remains dismal. To combat the aggressiveness and drug resistance of Epstein-Barr virus (EBV)-positive Head-Neck cancer cells, this study looks into the potential of Euphorbia tirucalli (pencil cactus) leaf extract. Objectives: The goal of this study is to identify prospective therapeutic candidates from the extract of Euphorbia tirucalli (pencil cactus) leaves, which have the ability to inhibit Epstein-Barr virus (EBV)-positive Head-Neck cancer cells. Materials and Methods: The thirteen most important chemical components found in Euphorbia tirucalli (pencil cactus) leaves were analyzed by means of molecular modeling techniques such as Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET), Quantum Mechanics (QM) calculation, Molecular Dynamics (MD) profiling, molecular docking, and molecular dynamics (MD) simulations. Using the Prediction of Activity Spectra for Substances (PASS) model, we assess the potency of these compounds in vitro against an Epstein- Barr virus (EBV)-positive head-neck cancer cell line. Important molecular properties such as chemical potential, electronegativity, hardness, and softness can be determined with the use of quantum chemical calculations employing HOMO-LUMO analysis. These drugs' safety and toxicological characteristics are better understood thanks to assessments of their pharmacokinetics and ADMET. These tests show that there is no risk of hepatotoxicity or cancer in humans and that they are safe to use. In order to verify binding interactions and complex stability, molecular dynamics simulations are used to reveal stable docked complexes. Results: The molecular docking analysis identifies ligands (01), (02), and (10) as strong competitors, with strong binding affinity for the Epstein-Barr virus (EBV)-positive Head-Neck cancer cell line. Not only do the ligands (01), (02), and (10) match the criteria for a potential new inhibitor of head-neck cancer, but they also outperform the present FDA-approved treatment. Conclusion: Taraxerol, euphol, and ephorginol, three phytochemicals isolated from the leaves of the Euphorbia tirucalli (pencil cactus), have been identified as effective anti-cancer agents with the potential to serve as a foundation for novel head-neck cancer therapies, particularly those targeting the Epstein-Barr virus (EBV)-overexpressing subtype of this disease. An effective, individualized treatment plan for head-neck cancer is a long way off, but this study is a major step forward that could change the lives of patients and lessen the global burden of this disease.
{"title":"New Approach as Inhibitor Against Head-Neck Cancer by In silico, DFT, FMOs, Docking, Molecular Dynamic, and ADMET of Euphorbia tirucalli (Pencil Cactus)","authors":"Md. Abdullah Al Mashud, Ramprosad Devnath, Masuma Anzuman, Mahbuba Iasmin Sumona, Md. Shamim Hossain, Ajoy Kumer, Md. Enamul Kabir Talukder, Md. Mashiar Rahman, Raihan Rahman Imon, Shopnil Akash, Abdelfattah El Moussaoui, Ahmad Mohammad Salamatullah, Mohammed Bourhia","doi":"10.2174/0115734064315601240628115330","DOIUrl":"https://doi.org/10.2174/0115734064315601240628115330","url":null,"abstract":"Background: Head and neck cancer (HNC) is on the rise worldwide, endangering lives and straining healthcare systems in both developing and developed nations. Despite the availability of a number of therapy options, the success rate for treating and controlling head and neck cancer remains dismal. To combat the aggressiveness and drug resistance of Epstein-Barr virus (EBV)-positive Head-Neck cancer cells, this study looks into the potential of Euphorbia tirucalli (pencil cactus) leaf extract. Objectives: The goal of this study is to identify prospective therapeutic candidates from the extract of Euphorbia tirucalli (pencil cactus) leaves, which have the ability to inhibit Epstein-Barr virus (EBV)-positive Head-Neck cancer cells. Materials and Methods: The thirteen most important chemical components found in Euphorbia tirucalli (pencil cactus) leaves were analyzed by means of molecular modeling techniques such as Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET), Quantum Mechanics (QM) calculation, Molecular Dynamics (MD) profiling, molecular docking, and molecular dynamics (MD) simulations. Using the Prediction of Activity Spectra for Substances (PASS) model, we assess the potency of these compounds in vitro against an Epstein- Barr virus (EBV)-positive head-neck cancer cell line. Important molecular properties such as chemical potential, electronegativity, hardness, and softness can be determined with the use of quantum chemical calculations employing HOMO-LUMO analysis. These drugs' safety and toxicological characteristics are better understood thanks to assessments of their pharmacokinetics and ADMET. These tests show that there is no risk of hepatotoxicity or cancer in humans and that they are safe to use. In order to verify binding interactions and complex stability, molecular dynamics simulations are used to reveal stable docked complexes. Results: The molecular docking analysis identifies ligands (01), (02), and (10) as strong competitors, with strong binding affinity for the Epstein-Barr virus (EBV)-positive Head-Neck cancer cell line. Not only do the ligands (01), (02), and (10) match the criteria for a potential new inhibitor of head-neck cancer, but they also outperform the present FDA-approved treatment. Conclusion: Taraxerol, euphol, and ephorginol, three phytochemicals isolated from the leaves of the Euphorbia tirucalli (pencil cactus), have been identified as effective anti-cancer agents with the potential to serve as a foundation for novel head-neck cancer therapies, particularly those targeting the Epstein-Barr virus (EBV)-overexpressing subtype of this disease. An effective, individualized treatment plan for head-neck cancer is a long way off, but this study is a major step forward that could change the lives of patients and lessen the global burden of this disease.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219151","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 : 2024-08-26DOI: 10.2174/0115734064324855240806052735
Jose Manuel Mendez-Arriaga
Background: Globally, parasitic diseases are considered among the neglected diseases. Clinically, several drugs are used in treatment, however due to drug resistance and multidrug resistance and the low investment in new research lines, there has been a failure in the treatment of parasitic illnesses. Objectives: The present mini-review is a comprehensive review of the use of platinum group metals as biological agents. It aims to establish the actual state of the art of these metal elements in the antiparasitic activity-specific area and define the future possibilities of action. Methods: The review comprises more than 100 research works done in this field. The differences between platinum group metals chemistry and their use as metal complexes with biological activity have been discussed. Results: This review highlighted the platinum group metal's potential as an antiparasitic agent for different diseases. Conclusion: The review will be helpful for the researchers involved in targeted drugs for parasitic disease therapy.
{"title":"Platinum Group Metals against Parasites: State of the Art and Future Perspectives","authors":"Jose Manuel Mendez-Arriaga","doi":"10.2174/0115734064324855240806052735","DOIUrl":"https://doi.org/10.2174/0115734064324855240806052735","url":null,"abstract":"Background: Globally, parasitic diseases are considered among the neglected diseases. Clinically, several drugs are used in treatment, however due to drug resistance and multidrug resistance and the low investment in new research lines, there has been a failure in the treatment of parasitic illnesses. Objectives: The present mini-review is a comprehensive review of the use of platinum group metals as biological agents. It aims to establish the actual state of the art of these metal elements in the antiparasitic activity-specific area and define the future possibilities of action. Methods: The review comprises more than 100 research works done in this field. The differences between platinum group metals chemistry and their use as metal complexes with biological activity have been discussed. Results: This review highlighted the platinum group metal's potential as an antiparasitic agent for different diseases. Conclusion: The review will be helpful for the researchers involved in targeted drugs for parasitic disease therapy.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219154","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 : 2024-08-12DOI: 10.2174/0115734064316022240801093905
Hoang Minh Phan, Tan Thanh Mai, Thinh Nguyen Quang Don, Dat Thanh Do, Khac Minh Thai, Thanh Dao Tran, Phuong Truong, Phuong Nguyen Hoai Huynh
Introduction: Chalcone compounds exhibit diverse bioactivities, attracting significant interest. Morpholine is a heterocycle commonly used in medicinal chemistry. It could enhance the potency, pharmacokinetics, and bioactivities of its compounds. Method: Adding morpholine into the chalcone scaffold could help create new compounds with favorable bioactivities. In this study, a new parallel synthesis procedure has been developed. Using this procedure, 18 novel morpholinoalkoxychalcones have been successfully synthesized. They had chains with morpholine appended on ring A or ring B. All the synthesized compounds were evaluated for the antibacterial and antifungal activities by agar diffusion method on 5 bacteria and 2 fungi strains. Results: The compounds with good inhibition were determined with respect to the MIC values by the agar dilution method. Among the tested compounds, B.21 was found to be the best against S. faecalis, with an MIC value of 0.6 mM. B.43 was found to be the best against A. niger and C. albicans with MIC value of 2.04 mM. Conclusion: The in silico study has revealed two targets to align with the in vitro results. Longer alkyl chains have enhanced the activity, along with the presence of OH, NH2, and halogen groups on both rings A and B. result: We synthesis 18 new morpholinoalkoxychalcones with the chain both on ring A and ring B. All compounds are new based on Scifinder at 10/2023. 3 compounds showed intermediate activity on 5 bacteria strains and 8 compounds showed intermediate activity on 2 fungi strains. The in silico study showed that there were 2 targets suitable with the in vitro results.
简介：查耳酮化合物具有多种生物活性，引起了人们的极大兴趣。吗啉是药物化学中常用的杂环。它可以增强其化合物的药效、药代动力学和生物活性。研究方法在查尔酮支架中加入吗啉有助于创造具有良好生物活性的新化合物。本研究开发了一种新的平行合成程序。利用这一程序，成功合成了 18 种新型吗啉烷氧基查尔酮。通过琼脂扩散法对 5 种细菌和 2 种真菌菌株进行了抗菌和抗真菌活性评估。结果：通过琼脂稀释法测定了具有良好抑菌作用的化合物的 MIC 值。在测试的化合物中，B.21 对粪肠球菌的抑制效果最好，MIC 值为 0.6 mM。B.43 对 A. niger 和 C. albicans 的作用最好，MIC 值为 2.04 mM。结论：硅学研究发现了两个与体外研究结果一致的靶点。较长的烷基链增强了活性，同时 A 环和 B 环上都存在 OH、NH2 和卤素基团：我们合成了 18 种新的吗啉基烷氧基查耳酮，其 A 环和 B 环上都有链。3 个化合物对 5 种细菌菌株显示出中等活性，8 个化合物对 2 种真菌菌株显示出中等活性。硅学研究表明，有 2 个目标与体外结果相吻合。
{"title":"Synthesis and Evaluation of Antibacterial and Antifungal Activities In vitro and In silico of Novel Morpholinoalkoxychalcones","authors":"Hoang Minh Phan, Tan Thanh Mai, Thinh Nguyen Quang Don, Dat Thanh Do, Khac Minh Thai, Thanh Dao Tran, Phuong Truong, Phuong Nguyen Hoai Huynh","doi":"10.2174/0115734064316022240801093905","DOIUrl":"https://doi.org/10.2174/0115734064316022240801093905","url":null,"abstract":"Introduction: Chalcone compounds exhibit diverse bioactivities, attracting significant interest. Morpholine is a heterocycle commonly used in medicinal chemistry. It could enhance the potency, pharmacokinetics, and bioactivities of its compounds. Method: Adding morpholine into the chalcone scaffold could help create new compounds with favorable bioactivities. In this study, a new parallel synthesis procedure has been developed. Using this procedure, 18 novel morpholinoalkoxychalcones have been successfully synthesized. They had chains with morpholine appended on ring A or ring B. All the synthesized compounds were evaluated for the antibacterial and antifungal activities by agar diffusion method on 5 bacteria and 2 fungi strains. Results: The compounds with good inhibition were determined with respect to the MIC values by the agar dilution method. Among the tested compounds, B.21 was found to be the best against S. faecalis, with an MIC value of 0.6 mM. B.43 was found to be the best against A. niger and C. albicans with MIC value of 2.04 mM. Conclusion: The in silico study has revealed two targets to align with the in vitro results. Longer alkyl chains have enhanced the activity, along with the presence of OH, NH2, and halogen groups on both rings A and B. result: We synthesis 18 new morpholinoalkoxychalcones with the chain both on ring A and ring B. All compounds are new based on Scifinder at 10/2023. 3 compounds showed intermediate activity on 5 bacteria strains and 8 compounds showed intermediate activity on 2 fungi strains. The in silico study showed that there were 2 targets suitable with the in vitro results.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219153","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}
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