Pub Date : 2023-10-30DOI: 10.2174/0115701808248336230921100850
khushal kapadiya, Reshmabanu Piludiya
Background:: Multicomponent reactions (MCRs) have proven as one of the best alternatives to minimize several environmental consequences, mainly the use of hazardous chemicals, byproducts, and severe production processes. Literature reveals that MCRs with PEG-400 and metal oxide-based greener media provide a new and useful strategy for the construction of biologically potent organic systems. Objective:: The present study aimed to synthesize newer Betti bases by a modified Betti reaction employing a highly efficient catalyst for the direct synthesis of a novel class of non-racemic amino benzyl naphthol ligands under green solvent media. The involvement of the articulated framework (4a-4j) was studied against nine cancer panels (NCI-60 cell lines) in terms of inhibiting/killing cancer cells. Methods:: For the modification of the Betti reaction, we used 2-aminopyridin-3-ol, aromatic aldehydes, and a naphthol system using greener media employing PEG-400 and alumina as a prime active and highly selective catalyst. Furthermore, the antiproliferative activity against NCI-60 human cancer cell lines (GI50) was used for the development of pharmacologically active compounds and exhibited the single dose (10-5 M) study. Results:: Based on greener media synthesis, recompenses of ease of workup, less reaction time, higher yield, and higher atom economy, as well as environmentally friendly, were reported. Betti bases were obtained at a yield of 87-98% and characterized by spectroscopic techniques. Among the synthesized scaffolds, compound 4b was found to be extra potent in melanoma cancer [MDAMB- 435], while compound 4h showed promising inhibition in leukemic cancer cell lines [HL- 60(TB) and MOLT-4]. Conclusion:: A straightforward way for an efficient synthesis of Betti bases was developed via the reaction of naphthol and aldehydes with amines in PEG-400 media. An Al2O3 was effectively catalyzed in the Betti reaction in excellent yields without the formation of any other by-product in atom economy and environmentally benign way. The newly synthesized hybrids were tested in vitro against a panel of cancer cell lines, and some of the compounds exhibited significant inhibitory anti-proliferative effects. The most potent compounds (4b and 4h) showed interesting results, and compound 4b was found extra potent in melanoma cancer cell lines with -62% GI values.
{"title":"Highly Efficient and One-pot New Betti Bases: PEG-400 and Al2O3 Mediated Synthesis, Optimizations, and Cytotoxic Studies","authors":"khushal kapadiya, Reshmabanu Piludiya","doi":"10.2174/0115701808248336230921100850","DOIUrl":"https://doi.org/10.2174/0115701808248336230921100850","url":null,"abstract":"Background:: Multicomponent reactions (MCRs) have proven as one of the best alternatives to minimize several environmental consequences, mainly the use of hazardous chemicals, byproducts, and severe production processes. Literature reveals that MCRs with PEG-400 and metal oxide-based greener media provide a new and useful strategy for the construction of biologically potent organic systems. Objective:: The present study aimed to synthesize newer Betti bases by a modified Betti reaction employing a highly efficient catalyst for the direct synthesis of a novel class of non-racemic amino benzyl naphthol ligands under green solvent media. The involvement of the articulated framework (4a-4j) was studied against nine cancer panels (NCI-60 cell lines) in terms of inhibiting/killing cancer cells. Methods:: For the modification of the Betti reaction, we used 2-aminopyridin-3-ol, aromatic aldehydes, and a naphthol system using greener media employing PEG-400 and alumina as a prime active and highly selective catalyst. Furthermore, the antiproliferative activity against NCI-60 human cancer cell lines (GI50) was used for the development of pharmacologically active compounds and exhibited the single dose (10-5 M) study. Results:: Based on greener media synthesis, recompenses of ease of workup, less reaction time, higher yield, and higher atom economy, as well as environmentally friendly, were reported. Betti bases were obtained at a yield of 87-98% and characterized by spectroscopic techniques. Among the synthesized scaffolds, compound 4b was found to be extra potent in melanoma cancer [MDAMB- 435], while compound 4h showed promising inhibition in leukemic cancer cell lines [HL- 60(TB) and MOLT-4]. Conclusion:: A straightforward way for an efficient synthesis of Betti bases was developed via the reaction of naphthol and aldehydes with amines in PEG-400 media. An Al2O3 was effectively catalyzed in the Betti reaction in excellent yields without the formation of any other by-product in atom economy and environmentally benign way. The newly synthesized hybrids were tested in vitro against a panel of cancer cell lines, and some of the compounds exhibited significant inhibitory anti-proliferative effects. The most potent compounds (4b and 4h) showed interesting results, and compound 4b was found extra potent in melanoma cancer cell lines with -62% GI values.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136132364","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}
Abstract: An energetic desire to reduce the undesirable effects brought on by synthetic heterocyclic substances and to combat antimicrobial resistance has led to an increase in curiosity in using natural antimicrobial agents derived from plants, such as phenolics, catechol, pyrogallol, essential oils, Lchicoric acid, caffeic acid, catechins, coumarin, proanthocyanidins, 4-thiazolidinone, and alkaloids. The usage of naturally occurring heterocycles against Gram-positive (S. aureus, S. pyogenes, B. subtilis, A. niger, and B. cereus) and Gram-negative (P. aeruginosa, E. coli, K. pneumonia, P. vulgaris, and S. infantis) bacteria has been the subject of increased investigation in past few decades. This review targets the use of plant-derived antimicrobials to increase the microbiological safety of food and the possible antimicrobial activity of nitrogen- and oxygen-based heterocyclic compounds. It is possible to find novel medications to treat infectious diseases and address the issues brought on by antibiotic resistance by exploring and utilising the potential of these chemicals. Additional research is desirable on the toxicological effects and potential additive and/or synergistic antimicrobial actions in order to maximise the usage of these potential natural antimicrobials in foods.
{"title":"An Emerging Class of Antimicrobial Heterocycles Derived from Natural Sources","authors":"Benu Chaudhary, Babita Patial, Rajiv Sharma, Anshul Chawla","doi":"10.2174/0115701808254524231018040600","DOIUrl":"https://doi.org/10.2174/0115701808254524231018040600","url":null,"abstract":"Abstract: An energetic desire to reduce the undesirable effects brought on by synthetic heterocyclic substances and to combat antimicrobial resistance has led to an increase in curiosity in using natural antimicrobial agents derived from plants, such as phenolics, catechol, pyrogallol, essential oils, Lchicoric acid, caffeic acid, catechins, coumarin, proanthocyanidins, 4-thiazolidinone, and alkaloids. The usage of naturally occurring heterocycles against Gram-positive (S. aureus, S. pyogenes, B. subtilis, A. niger, and B. cereus) and Gram-negative (P. aeruginosa, E. coli, K. pneumonia, P. vulgaris, and S. infantis) bacteria has been the subject of increased investigation in past few decades. This review targets the use of plant-derived antimicrobials to increase the microbiological safety of food and the possible antimicrobial activity of nitrogen- and oxygen-based heterocyclic compounds. It is possible to find novel medications to treat infectious diseases and address the issues brought on by antibiotic resistance by exploring and utilising the potential of these chemicals. Additional research is desirable on the toxicological effects and potential additive and/or synergistic antimicrobial actions in order to maximise the usage of these potential natural antimicrobials in foods.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136316942","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 : 2023-10-27DOI: 10.2174/0115701808269296231019055844
Lili Su, Zixian Wang, Pengli Guo, Zhongmei He, Jianming Li, Yan Zhao, Ying Zong, Weijia Chen, Rui Du
Background:: Paeoniflorin has been proven to have neuroprotective and antidepressant effects in several studies. However, there is currently no comprehensive elaboration of its antidepressant effects through network pharmacology combined with transcriptomics analysis. The purpose of this study is to explore the potential mechanisms by which paeoniflorin exerts its antidepressant effects using network pharmacology and transcriptomics sequencing approaches. Methods:: We utilized metascape to enrich the intersecting targets for paeoniflorin and depression for enrichment analyses. Additionally, we employed Cytoscape software to construct target pathway networks. For the screening of differentially expressed genes (DEGs) altered by paeoniflorin, we sequenced mRNA from the hippocampal tissue of CUMS model mice using the BMKCloud platform. We further enriched their biological functions and signaling pathways by using the Omishare database. The study utilized a combination of network pharmacology and transcriptomics analysis to evaluate the interactions between paeoniflorin and key targets. The results were then verified through a molecular docking process and a subsequent Western blot experiment. Results:: According to a comprehensive analysis, paeoniflorin has 19 key targets that are closely related to its therapeutic effect. Molecular docking revealed that paeoniflorin has a high affinity for HIF-1α, VEGFA, and other targets. Furthermore, protein expression and immunofluorescence staining analysis showed that paeoniflorin significantly increased the expression level of HIF-1α and VEGFA in the hippocampus of depression model mice. Conclusion:: These findings suggest that paeoniflorin may have therapeutic potential in depression through the activation of the HIF-1α-VEGFA pathway.
{"title":"Integrating Network Pharmacology and Transcriptomic Strategies to Explore the Pharmacological Mechanism of Paeoniflorin Exerts Antidepressant Effects","authors":"Lili Su, Zixian Wang, Pengli Guo, Zhongmei He, Jianming Li, Yan Zhao, Ying Zong, Weijia Chen, Rui Du","doi":"10.2174/0115701808269296231019055844","DOIUrl":"https://doi.org/10.2174/0115701808269296231019055844","url":null,"abstract":"Background:: Paeoniflorin has been proven to have neuroprotective and antidepressant effects in several studies. However, there is currently no comprehensive elaboration of its antidepressant effects through network pharmacology combined with transcriptomics analysis. The purpose of this study is to explore the potential mechanisms by which paeoniflorin exerts its antidepressant effects using network pharmacology and transcriptomics sequencing approaches. Methods:: We utilized metascape to enrich the intersecting targets for paeoniflorin and depression for enrichment analyses. Additionally, we employed Cytoscape software to construct target pathway networks. For the screening of differentially expressed genes (DEGs) altered by paeoniflorin, we sequenced mRNA from the hippocampal tissue of CUMS model mice using the BMKCloud platform. We further enriched their biological functions and signaling pathways by using the Omishare database. The study utilized a combination of network pharmacology and transcriptomics analysis to evaluate the interactions between paeoniflorin and key targets. The results were then verified through a molecular docking process and a subsequent Western blot experiment. Results:: According to a comprehensive analysis, paeoniflorin has 19 key targets that are closely related to its therapeutic effect. Molecular docking revealed that paeoniflorin has a high affinity for HIF-1α, VEGFA, and other targets. Furthermore, protein expression and immunofluorescence staining analysis showed that paeoniflorin significantly increased the expression level of HIF-1α and VEGFA in the hippocampus of depression model mice. Conclusion:: These findings suggest that paeoniflorin may have therapeutic potential in depression through the activation of the HIF-1α-VEGFA pathway.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136318557","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: Methamphetamine (METH) is a highly addictive neural stimulant that severely affects the CNS and can induce oxidative damage. Piperine and curcumin are active constituents that have numerous properties, including antioxidant, anti-inflammatory, and neuroprotective Objective: In this study, the synergistic effect of piperine and curcumin nanoparticles was investigated on the acute doses of METH-induced neurotoxicity in mice brains. Methods: METH (6 mg/kg, i.p) was administered to 14 groups of mice and piperine-curcumin nanoparticles at different doses (10, 20, 40 mg/kg and 20, 40 and 60 mg/kg, respectively) were administered. Open field test (OFT) and conditioned place preference (CPP) were used to investigate locomotor activity, anxiety-like behavior, and addictive behavior in mice. Oxidative stress biomarkers (reactive oxygen species (ROS), protein carbonyl content, lipid peroxidation, glutathione content, and mitochondrial function were evaluated in isolated brain mitochondria. Results: We found that piperine and curcumin nanoparticles significantly decreased hyperlocomotion and anxiety-like behavior in METH-treated mice. Also, METH enhanced CPP whilst piperine and curcumin nanoparticles suppressed the effect of METH-induced CPP. METH administration significantly increased ROS, protein carbonyl content, and lipid peroxidation and decreased glutathione content and mitochondrial function in the isolated brain mitochondria. Piperine and curcumin nanoparticles (at all doses) showed synergistic effects on reducing oxidative damages in a dosedependent manner compared to the METH group. Conclusion: In conclusion, combined piperine and curcumin nanoparticles showed greater neuroprotective effects against METH-induced neurotoxicity due to their greater permeability and better antioxidant properties than piperine and curcumin alone
{"title":"The Synergistic Effect of Curcumin and Piperine Nanoparticles on Methamphetamine-induced Neurotoxicity, Oxidative Stress, and Memory Impairments in Mice Brain","authors":"Pedram Ebrahimnejad, Hamed Ghazvini, Parisa Hasanjani, Parisa Saberi-Hasanabadi, Javad Akhtari, Hamidreza Mohammadi","doi":"10.2174/0115701808249823231017103251","DOIUrl":"https://doi.org/10.2174/0115701808249823231017103251","url":null,"abstract":"Background: Methamphetamine (METH) is a highly addictive neural stimulant that severely affects the CNS and can induce oxidative damage. Piperine and curcumin are active constituents that have numerous properties, including antioxidant, anti-inflammatory, and neuroprotective Objective: In this study, the synergistic effect of piperine and curcumin nanoparticles was investigated on the acute doses of METH-induced neurotoxicity in mice brains. Methods: METH (6 mg/kg, i.p) was administered to 14 groups of mice and piperine-curcumin nanoparticles at different doses (10, 20, 40 mg/kg and 20, 40 and 60 mg/kg, respectively) were administered. Open field test (OFT) and conditioned place preference (CPP) were used to investigate locomotor activity, anxiety-like behavior, and addictive behavior in mice. Oxidative stress biomarkers (reactive oxygen species (ROS), protein carbonyl content, lipid peroxidation, glutathione content, and mitochondrial function were evaluated in isolated brain mitochondria. Results: We found that piperine and curcumin nanoparticles significantly decreased hyperlocomotion and anxiety-like behavior in METH-treated mice. Also, METH enhanced CPP whilst piperine and curcumin nanoparticles suppressed the effect of METH-induced CPP. METH administration significantly increased ROS, protein carbonyl content, and lipid peroxidation and decreased glutathione content and mitochondrial function in the isolated brain mitochondria. Piperine and curcumin nanoparticles (at all doses) showed synergistic effects on reducing oxidative damages in a dosedependent manner compared to the METH group. Conclusion: In conclusion, combined piperine and curcumin nanoparticles showed greater neuroprotective effects against METH-induced neurotoxicity due to their greater permeability and better antioxidant properties than piperine and curcumin alone","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136316763","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 : 2023-10-25DOI: 10.2174/0115701808245049231019095755
Girish Chandra Arya, Rajiv Sharma, Shefali Mehla
Background: Colorectal cancer is the third foremost cause of death in women and men. Globally, about 1.94 million colon cancer cases were diagnosed and around 0.93 million patients died in the previous year. Introduction: Several drugs have been permitted by the Food And Drug Administration (FDA) for the treatment of colorectal cancer. The main difficulties of current drugs are the expansion of resistance issues, target selectivity issues and toxicity issues. The existing therapies, such as surgery and hormonal therapy, are in use but exhibit numerous adverse effects, such as pharmacokinetic issues and pharmacodynamic issues. Hence, hereby is a crucial requirement of novel moieties that are peaceable and efficient in the handling of colorectal cancer. Method: Phthalazine derivatives have expanded admiration over a few years due to their efficient anticancer significance. These Phthalazine derivatives exhibit anticancer activity by targeting various mechanisms such as apoptosis induction, tubulin polymerization inhibition, EGFR inhibition, and aurora kinase inhibition. Result: In this study, we have focused on the Structural Activity relationship, numerous synthetic strategies and mechanism of action of phthalazine derivatives for potential treatment of cancer. Conclusion: Among some of phthalazine derivative compounds not only induced antiproliferative activity even also improved bioavailability and reduced side effects, like 4-(phthalazine-1-yl) aniline with (IC50 = 0.22 ± 0.11 μM), and 4-phthalazin-1-yl-amino) benzonitrile (IC50 = 1.20 μM), 4-((5- methyl-pyrazole-3-yl) amino)-2-phenylphthalazin-1-one (IC50 = 0.031 μM) and 4-((5-methylpyrazole- 3-yl) amino)-2-(p-tolyl)phthalazin-1-one (IC50 = 0.065 μM). Therefore, this study would be the inspiration for the betterment of human health.
{"title":"A Concise Review of Synthetic Strategy, Mechanism of Action, and SAR Studies of Phthalazine Derivatives as Anticancer Agent","authors":"Girish Chandra Arya, Rajiv Sharma, Shefali Mehla","doi":"10.2174/0115701808245049231019095755","DOIUrl":"https://doi.org/10.2174/0115701808245049231019095755","url":null,"abstract":"Background: Colorectal cancer is the third foremost cause of death in women and men. Globally, about 1.94 million colon cancer cases were diagnosed and around 0.93 million patients died in the previous year. Introduction: Several drugs have been permitted by the Food And Drug Administration (FDA) for the treatment of colorectal cancer. The main difficulties of current drugs are the expansion of resistance issues, target selectivity issues and toxicity issues. The existing therapies, such as surgery and hormonal therapy, are in use but exhibit numerous adverse effects, such as pharmacokinetic issues and pharmacodynamic issues. Hence, hereby is a crucial requirement of novel moieties that are peaceable and efficient in the handling of colorectal cancer. Method: Phthalazine derivatives have expanded admiration over a few years due to their efficient anticancer significance. These Phthalazine derivatives exhibit anticancer activity by targeting various mechanisms such as apoptosis induction, tubulin polymerization inhibition, EGFR inhibition, and aurora kinase inhibition. Result: In this study, we have focused on the Structural Activity relationship, numerous synthetic strategies and mechanism of action of phthalazine derivatives for potential treatment of cancer. Conclusion: Among some of phthalazine derivative compounds not only induced antiproliferative activity even also improved bioavailability and reduced side effects, like 4-(phthalazine-1-yl) aniline with (IC50 = 0.22 ± 0.11 μM), and 4-phthalazin-1-yl-amino) benzonitrile (IC50 = 1.20 μM), 4-((5- methyl-pyrazole-3-yl) amino)-2-phenylphthalazin-1-one (IC50 = 0.031 μM) and 4-((5-methylpyrazole- 3-yl) amino)-2-(p-tolyl)phthalazin-1-one (IC50 = 0.065 μM). Therefore, this study would be the inspiration for the betterment of human health.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135218849","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 : 2023-10-23DOI: 10.2174/0115701808274204231012111936
Meng Ji, Ji-hua Xu, He-yin Mi, Peng Jiang, Yue Li
Objective: Vinpocetine (Vinp), a derivative of alkaloid vincristine with anti-inflammatory and antioxidant effects, has been shown to have neuroprotective effects in Parkinson's disease (PD). Its role and mechanisms, however, are not fully understood. Therefore, the aim of this study was to investigate the effects and possible mechanisms of Vinp on PD cells. Methods: SH-SY5Y cells were treated with Vinp and then with rotenone to induce a cellular model of PD. The proliferation level and apoptosis rate of SH-SY5Y cells after different treatments were detected by MTT and flow cytometry assays, respectively. Western blot was used to determine the relative protein expression of α-Synuclein (α-Syn) in differently treated cells. Additionally, commercial kits and ELISA were used to determine oxidative stress-related indicators (superoxide dismutase [SOD], malondialdehyde [MDA], and reactive oxygen species [ROS]) and inflammatory factors (tumor necrosis factor α [TNF-α], interleukin-5 [IL-5], and interleukin-1β [IL-1β]) in SH-SY5Y cells after different treatments, respectively. Results: Vinp at different concentrations (5, 10, and 50 µM) had no significant effect on the proliferation and apoptosis of SH-SY5Y cells. For rotenone-induced SH-SY5Y cells, Vinp pretreatment could significantly reduce α-Syn expression, increased cell viability and decreased apoptosis, oxidative stress (downregulation of ROS and MDA levels and upregulation of SOD activity) and inflammation (increased levels of TNF-α, IL-5, and IL-1β). In contrast, overexpression of α-Syn in SHSY5Y cells with Vinp pretreatment and rotenone induction partially reversed the aforementioned protective effects of Vinp, causing a decrease in proliferation, an increase in apoptosis rate, inflammation, and oxidative stress. Conclusion: Vinp exerted neuroprotective effects by downregulating α-Syn to promote proliferation, inhibit apoptosis, and inhibit oxidative stress and inflammation in rotenone-induced SH-SY5Y cells.
{"title":"Vinpocetine Exerts Neuroprotective Effects via Downregulating α-Syn in Rotenone-induced Cellular Models of Parkinson’s Disease","authors":"Meng Ji, Ji-hua Xu, He-yin Mi, Peng Jiang, Yue Li","doi":"10.2174/0115701808274204231012111936","DOIUrl":"https://doi.org/10.2174/0115701808274204231012111936","url":null,"abstract":"Objective: Vinpocetine (Vinp), a derivative of alkaloid vincristine with anti-inflammatory and antioxidant effects, has been shown to have neuroprotective effects in Parkinson's disease (PD). Its role and mechanisms, however, are not fully understood. Therefore, the aim of this study was to investigate the effects and possible mechanisms of Vinp on PD cells. Methods: SH-SY5Y cells were treated with Vinp and then with rotenone to induce a cellular model of PD. The proliferation level and apoptosis rate of SH-SY5Y cells after different treatments were detected by MTT and flow cytometry assays, respectively. Western blot was used to determine the relative protein expression of α-Synuclein (α-Syn) in differently treated cells. Additionally, commercial kits and ELISA were used to determine oxidative stress-related indicators (superoxide dismutase [SOD], malondialdehyde [MDA], and reactive oxygen species [ROS]) and inflammatory factors (tumor necrosis factor α [TNF-α], interleukin-5 [IL-5], and interleukin-1β [IL-1β]) in SH-SY5Y cells after different treatments, respectively. Results: Vinp at different concentrations (5, 10, and 50 µM) had no significant effect on the proliferation and apoptosis of SH-SY5Y cells. For rotenone-induced SH-SY5Y cells, Vinp pretreatment could significantly reduce α-Syn expression, increased cell viability and decreased apoptosis, oxidative stress (downregulation of ROS and MDA levels and upregulation of SOD activity) and inflammation (increased levels of TNF-α, IL-5, and IL-1β). In contrast, overexpression of α-Syn in SHSY5Y cells with Vinp pretreatment and rotenone induction partially reversed the aforementioned protective effects of Vinp, causing a decrease in proliferation, an increase in apoptosis rate, inflammation, and oxidative stress. Conclusion: Vinp exerted neuroprotective effects by downregulating α-Syn to promote proliferation, inhibit apoptosis, and inhibit oxidative stress and inflammation in rotenone-induced SH-SY5Y cells.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135460553","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 : 2023-10-20DOI: 10.2174/0115701808273623231009074241
Ricardo Silva Porto, Viviane Amaral Porto
Background: Cinnamic acid, derived from Cinnamomum cassia, is a natural compound known for its wide-ranging therapeutic properties and minimal toxicity. Extensive research has demonstrated the diverse biological activities displayed by cinnamic acid derivatives, encompassing their potential as agents against cancer, diabetes, microbial infections, tuberculosis, malaria, and more. Objective: This review aims to provide an overview of the latest applications detailing the biological activity of cinnamic acid derivatives, as documented in patents. Methods: The published patent data underwent a prior screening and selection process based on their relevance and primary focus: the biological activities of cinnamic acid derivatives as potential drugs. Espacenet, USPTO, and Google Patents were used for this selection. Results: Cinnamic acid derivatives demonstrate a range of activities, including anticancer, antibacterial, anti-inflammatory, analgesic, anticholinesterase, and other properties. These biological activities were investigated across different derivatives, emphasizing their pharmacological potential when compared to reference compounds. Conclusions: Despite several patents have explored the biological properties of cinnamic acid derivatives, there has been a lack of a comprehensive review dedicated to this subject. Accordingly, this review aims to facilitate the discovery of new and diverse potential drugs with various therapeutic profiles.
{"title":"Uncovering the Biological Applications of Cinnamic Acid Derivatives: A Patent Review","authors":"Ricardo Silva Porto, Viviane Amaral Porto","doi":"10.2174/0115701808273623231009074241","DOIUrl":"https://doi.org/10.2174/0115701808273623231009074241","url":null,"abstract":"Background: Cinnamic acid, derived from Cinnamomum cassia, is a natural compound known for its wide-ranging therapeutic properties and minimal toxicity. Extensive research has demonstrated the diverse biological activities displayed by cinnamic acid derivatives, encompassing their potential as agents against cancer, diabetes, microbial infections, tuberculosis, malaria, and more. Objective: This review aims to provide an overview of the latest applications detailing the biological activity of cinnamic acid derivatives, as documented in patents. Methods: The published patent data underwent a prior screening and selection process based on their relevance and primary focus: the biological activities of cinnamic acid derivatives as potential drugs. Espacenet, USPTO, and Google Patents were used for this selection. Results: Cinnamic acid derivatives demonstrate a range of activities, including anticancer, antibacterial, anti-inflammatory, analgesic, anticholinesterase, and other properties. These biological activities were investigated across different derivatives, emphasizing their pharmacological potential when compared to reference compounds. Conclusions: Despite several patents have explored the biological properties of cinnamic acid derivatives, there has been a lack of a comprehensive review dedicated to this subject. Accordingly, this review aims to facilitate the discovery of new and diverse potential drugs with various therapeutic profiles.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135618282","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: Mentha piperita, a naturally occurring herb, is utilized in medicinal formulations. It possesses abundant bioactive elements, including flavonoids and phenolic acid compounds,that exhibit various properties such as antioxidants, anti-inflammatory and anti-cancer. Objective: In the present study, chemical constituents of essential oil extracted from Mentha piperita were analyzed and identified through GC-MS. In vitro antiproliferative activity was performed on A549 lung cancer cell line lines. In silico study was conducted by Schrodinger’s Maestro’s software to identify chemical constituents in the plant as potential EGFR (Epidermal Growth Factor Receptors) inhibitors Methods: Hydro-distilled essential oil was analyzed by GC-MS to identify chemical components based on the retention index and mass fragmentation pattern, which was then tested for its antiproliferative activity by MTT assay against human lung cancer cell lines. All the identified constituents were investigated in silico for their affinity towards EGFR (Epidermal Growth Factor Receptors). Result: A total of thirty constituents were identified where D-carvone (56.69%), L-limonene (12.36%), squalene (3.36%), cis-carveol (2.93%), and α-amorphene (2.36%) were observed as major constituents of the essential oil. The essential mentha oil also exhibited antiproliferative activity against lung cancer cell lines with an IC50 value of 86.05 µg/ml. Furthermore, from the in silico study, five constituents were identified to have a better affinity for EGFR (Epidermal Growth Factor Receptors) than that of the standard drug Osimertinib. Conclusion: In the present study, the aerial part of the plant Mentha piperita was hydrodistilled.Thirty phytoconstituents were identified through GC-MS data. An in-silico study was performed using Schrodinger software, and a further in vitro study was performed in which essential oil showedgood antiproliferative activity against the A549 cancer cell line.
{"title":"Chemical Composition, In Vitro and In silico Evaluation of Essential Oil Extracted from Mentha Piperita L. for Lung Cancer","authors":"Bhim Singh, Amit Kumar, Kumari Sunita Prajapati, Shivam Patel, Shashank Kumar, Vikas Jaitak","doi":"10.2174/0115701808266939231011044527","DOIUrl":"https://doi.org/10.2174/0115701808266939231011044527","url":null,"abstract":"Background: Mentha piperita, a naturally occurring herb, is utilized in medicinal formulations. It possesses abundant bioactive elements, including flavonoids and phenolic acid compounds,that exhibit various properties such as antioxidants, anti-inflammatory and anti-cancer. Objective: In the present study, chemical constituents of essential oil extracted from Mentha piperita were analyzed and identified through GC-MS. In vitro antiproliferative activity was performed on A549 lung cancer cell line lines. In silico study was conducted by Schrodinger’s Maestro’s software to identify chemical constituents in the plant as potential EGFR (Epidermal Growth Factor Receptors) inhibitors Methods: Hydro-distilled essential oil was analyzed by GC-MS to identify chemical components based on the retention index and mass fragmentation pattern, which was then tested for its antiproliferative activity by MTT assay against human lung cancer cell lines. All the identified constituents were investigated in silico for their affinity towards EGFR (Epidermal Growth Factor Receptors). Result: A total of thirty constituents were identified where D-carvone (56.69%), L-limonene (12.36%), squalene (3.36%), cis-carveol (2.93%), and α-amorphene (2.36%) were observed as major constituents of the essential oil. The essential mentha oil also exhibited antiproliferative activity against lung cancer cell lines with an IC50 value of 86.05 µg/ml. Furthermore, from the in silico study, five constituents were identified to have a better affinity for EGFR (Epidermal Growth Factor Receptors) than that of the standard drug Osimertinib. Conclusion: In the present study, the aerial part of the plant Mentha piperita was hydrodistilled.Thirty phytoconstituents were identified through GC-MS data. An in-silico study was performed using Schrodinger software, and a further in vitro study was performed in which essential oil showedgood antiproliferative activity against the A549 cancer cell line.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135619493","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 : 2023-10-20DOI: 10.2174/0115701808267565231012095231
Hui Gao, Hong Liu, Jingxuan Hou, Qingshan Gu, Meiqi Shi, Qingkun Wu, Lu Zheng
Abstract: Epidermal growth factor tyrosine kinase receptor (EGFR) is expressed in a variety of tumors and has become a new target for anti-cancer drugs. In recent years, small molecule inhibitors targeting EGFR have been reported extensively. In this study, the structure–activity relationship of 119 pyrimidine EGFR inhibitors were studied based on comparative field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMISA). Performant models with high predictive ability were constructed (CoMFA model: q2 = 0.574, r 2 = 0.970, SEE = 0.163, F = 407.252; CoMSIA model: q2 = 0.575, r 2 = 0.968, SEE = 0.171, F = 286.102), according to which 9 new EGFR inhibitors were designed. MD simulation (100 ns) on the docked complex of compound N7 (the most active compound) shows that the small molecule binds with the protein stably. MM/PBSA calculation provided the binding free energy of the compound N7, -37.18 kcal·mol-1, lower than the original ligand. Newly designed molecules showed promising results in ADMET prediction. These results will provide valuable guidance for the design of novel EGFR inhibitors
摘要表皮生长因子酪氨酸激酶受体(Epidermal growth factor tyrosine kinase receptor, EGFR)在多种肿瘤中表达，已成为抗癌药物的新靶点。近年来，针对EGFR的小分子抑制剂被广泛报道。本研究采用比较场分析(CoMFA)和比较分子相似指数分析(CoMISA)对119种嘧啶类EGFR抑制剂的构效关系进行了研究。构建了具有较高预测能力的绩效模型(CoMFA模型:q2 = 0.574, r 2 = 0.970, SEE = 0.163, F = 407.252;CoMSIA模型:q2 = 0.575, r 2 = 0.968, SEE = 0.171, F = 286.102)，据此设计出9种新的EGFR抑制剂。对化合物N7(活性最强的化合物)的对接物进行了100 ns的MD模拟，结果表明该小分子与蛋白质的结合稳定。MM/PBSA计算得到化合物N7的结合自由能为-37.18 kcal·mol-1，低于原配体。新设计的分子在ADMET预测中显示出良好的结果。这些结果将为新型EGFR抑制剂的设计提供有价值的指导
{"title":"3D-QSAR and Molecular Docking Studies of Pyrimidine-based EGFR Inhibitors","authors":"Hui Gao, Hong Liu, Jingxuan Hou, Qingshan Gu, Meiqi Shi, Qingkun Wu, Lu Zheng","doi":"10.2174/0115701808267565231012095231","DOIUrl":"https://doi.org/10.2174/0115701808267565231012095231","url":null,"abstract":"Abstract: Epidermal growth factor tyrosine kinase receptor (EGFR) is expressed in a variety of tumors and has become a new target for anti-cancer drugs. In recent years, small molecule inhibitors targeting EGFR have been reported extensively. In this study, the structure–activity relationship of 119 pyrimidine EGFR inhibitors were studied based on comparative field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMISA). Performant models with high predictive ability were constructed (CoMFA model: q2 = 0.574, r 2 = 0.970, SEE = 0.163, F = 407.252; CoMSIA model: q2 = 0.575, r 2 = 0.968, SEE = 0.171, F = 286.102), according to which 9 new EGFR inhibitors were designed. MD simulation (100 ns) on the docked complex of compound N7 (the most active compound) shows that the small molecule binds with the protein stably. MM/PBSA calculation provided the binding free energy of the compound N7, -37.18 kcal·mol-1, lower than the original ligand. Newly designed molecules showed promising results in ADMET prediction. These results will provide valuable guidance for the design of novel EGFR inhibitors","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135618643","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 : 2023-10-20DOI: 10.2174/0115701808243556231017055256
Dilan Konyar, Egemen Foto, Fatma Zilifdar Foto, Mehmet Erdem Buyukbingol
Background:: As cancer stands as a significant global health concern, many heterocyclic compounds that are more effective in cancer cells than healthy cells are being investigated for their selective anticancer potentials. One such compound is fenretinide, a synthetic derivative of retinoic acid that has a broad spectrum of cytotoxic activity against primary tumor cells, cell lines, and/or xenografts of various cancers. In this context, bexarotene and its derivatives, synthesized from hybridization of the fenretinide, are expected to possess a potential anticancer activity. background: Cancer is currently the most prevalent disease. It is already known that the Fenretinide compound shows biological activity template. The Fenretinide compound is obtained as a result of the amidification of the retinoic acid with p-hydroxy aniline. The Bexarotene compound and its derivatives that will be obtained as a result of the hybridization of the Fenretinide compound are expected to show anticancer activity. Objective:: The objective of the present study was to investigate the synthesis of novel amid-derived and bexarotene-based compounds, as well as to assess their cytotoxic effects in different cancer cell lines. objective: The purpose of this study was to analyze the synthesis of novel amid-derived compounds based on Bexarotene and cytotoxic effects in different cancer tissues. Methods:: This study involved the synthesis of twelve novel retinoid derivatives (6-17) in a six-step process. The cytotoxic activities of these compounds were assessed against various cancer cell lines, such as A549 (human lung carcinoma), HeLa (human cervical cancer), MCF7 (human breast adenocarcinoma), and WiDr (human colon adenocarcinoma). The chemical structures of these compounds were elucidated through their elemental analysis, mass spectrometry (ESI+, ESI-), as well as 1H-NMR and 13C-NMR spectroscopic data. method: In this study, novel twelve retinoid derivatives (6-17) were synthesized in six steps. Cytotoxic activities of the compounds have been tested against human lung carcinoma cells (A549), human cervical cancer cells (HeLa), human breast adenocarcinoma (MCF7), and human colon adenocarcinoma cell line (WiDr). The chemical structures of the compounds were explained with their elemental analysis, mass (ESI+, ESI-), and 1H-NMR, 13C-NMR spectral data. Results:: The obtained cell toxicity results indicated that compounds 6, 8, 11, 12, 13, 14, and 17 were found to exhibit the strongest cytotoxic activity in above mentioned cancer cell lines. The IC50 values for active compounds, 11 and 12, were determined as 2.38μM and 2.29μM, respectively. Remarkably, these compounds displayed higher cytotoxic activity in the WiDr cell line related to positive control, camptothecin (CPT). Moreover, compounds 14 and 17 demonstrated very similar level of cytotoxic activity to CPT, indicating their potential for antitumoral applications upon further studies. result: According to the obtained c
{"title":"Design, Synthesis, and Biological Evaluation of Some Novel Retinoid Derivatives","authors":"Dilan Konyar, Egemen Foto, Fatma Zilifdar Foto, Mehmet Erdem Buyukbingol","doi":"10.2174/0115701808243556231017055256","DOIUrl":"https://doi.org/10.2174/0115701808243556231017055256","url":null,"abstract":"Background:: As cancer stands as a significant global health concern, many heterocyclic compounds that are more effective in cancer cells than healthy cells are being investigated for their selective anticancer potentials. One such compound is fenretinide, a synthetic derivative of retinoic acid that has a broad spectrum of cytotoxic activity against primary tumor cells, cell lines, and/or xenografts of various cancers. In this context, bexarotene and its derivatives, synthesized from hybridization of the fenretinide, are expected to possess a potential anticancer activity. background: Cancer is currently the most prevalent disease. It is already known that the Fenretinide compound shows biological activity template. The Fenretinide compound is obtained as a result of the amidification of the retinoic acid with p-hydroxy aniline. The Bexarotene compound and its derivatives that will be obtained as a result of the hybridization of the Fenretinide compound are expected to show anticancer activity. Objective:: The objective of the present study was to investigate the synthesis of novel amid-derived and bexarotene-based compounds, as well as to assess their cytotoxic effects in different cancer cell lines. objective: The purpose of this study was to analyze the synthesis of novel amid-derived compounds based on Bexarotene and cytotoxic effects in different cancer tissues. Methods:: This study involved the synthesis of twelve novel retinoid derivatives (6-17) in a six-step process. The cytotoxic activities of these compounds were assessed against various cancer cell lines, such as A549 (human lung carcinoma), HeLa (human cervical cancer), MCF7 (human breast adenocarcinoma), and WiDr (human colon adenocarcinoma). The chemical structures of these compounds were elucidated through their elemental analysis, mass spectrometry (ESI+, ESI-), as well as 1H-NMR and 13C-NMR spectroscopic data. method: In this study, novel twelve retinoid derivatives (6-17) were synthesized in six steps. Cytotoxic activities of the compounds have been tested against human lung carcinoma cells (A549), human cervical cancer cells (HeLa), human breast adenocarcinoma (MCF7), and human colon adenocarcinoma cell line (WiDr). The chemical structures of the compounds were explained with their elemental analysis, mass (ESI+, ESI-), and 1H-NMR, 13C-NMR spectral data. Results:: The obtained cell toxicity results indicated that compounds 6, 8, 11, 12, 13, 14, and 17 were found to exhibit the strongest cytotoxic activity in above mentioned cancer cell lines. The IC50 values for active compounds, 11 and 12, were determined as 2.38μM and 2.29μM, respectively. Remarkably, these compounds displayed higher cytotoxic activity in the WiDr cell line related to positive control, camptothecin (CPT). Moreover, compounds 14 and 17 demonstrated very similar level of cytotoxic activity to CPT, indicating their potential for antitumoral applications upon further studies. result: According to the obtained c","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135666379","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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