Medicinal Chemistry最新文献

{"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":"13 1","pages":""},"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}

{"title":"Exploring Thiophene Derivatives: Synthesis Strategies and Biological Significance","authors":"Isha Mishra, Vikram Sharma, Nitin Kumar, Gaurav Krishna, Vandana Arora Sethi, Ravi Mittal, Prashant K. Dhakad, Raghav Mishra","doi":"10.2174/0115734064326879240801043412","DOIUrl":"https://doi.org/10.2174/0115734064326879240801043412","url":null,"abstract":"Objectives: Thiophene is one of the most important heterocyclic scaffolds with notable pharmacological properties. Thiophene and its derivatives are of particular interest among sulphurcontaining heterocycles because of their similarities to numerous natural and synthetic compounds with identified potential. The purpose of this study is to extensively analyse the synthetic pathways adopted for synthesising thiophene derivatives and investigate their various biological functions. Methods: A comprehensive review of the existing literature was conducted to collect data pertaining to the methods that are employed for the synthesis of thiophene derivatives. A comprehensive search was carried out through relevant databases, including work published in 2024. A variety of synthesis procedures were identified and arranged, encompassing both traditional approaches like the Gewald reaction and contemporary ones like microwave-assisted synthesis and green synthesis. In addition, a comprehensive compilation of in vitro and in vivo studies was conducted to investigate the biological effects of 50 distinct thiophene derivatives. The primary focus of the studies was on various activities such as anti-cancer, anti-inflammatory, antiprotozoal, antibacterial, antioxidant, and antiviral functions. Results: Diverse methodologies have been employed in the synthesis of thiophene derivatives, encompassing both conventional and modern methods. Furthermore, the biological potential of thiophene derivatives was investigated, demonstrating a broad range of actions. Key structural elements necessary for biological activity were clarified by investigations of the structure-activity relationship. Conclusion: The biological potential and flexible synthesis pathways of thiophene derivatives make them attractive candidates for use in medicinal and pharmaceutical chemistry. Understanding the different synthesis methods and biological actions of thiophene derivatives may assist rational design and create novel treatments for a variety of conditions. The potential for these compounds to be further explored and optimised is considerable for the next drug development initiatives.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"12 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219152","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}

{"title":"Crucial Structural Understanding for Selective HDAC8 Inhibition: Common Pharmacophores, Molecular Docking, Molecular Dynamics, and Zinc Binder Analysis of selective HDAC8 inhibitors.","authors":"Kakali Sarkar, Sudhan Debnath, Debanjan Sen, Supratik Kar, Samir Kumar Sil","doi":"10.2174/0115734064320232240709105228","DOIUrl":"https://doi.org/10.2174/0115734064320232240709105228","url":null,"abstract":"<p><strong>Background: </strong>Overexpression of HDAC8 was observed in various cancers and inhibition of HDAC8 has emerged as a promising therapeutic approach in recent decades.</p><p><strong>Objective: </strong>This review aims to facilitate the discovery of novel selective HDAC8 inhibitors by analyzing the structural scaffolds of 66 known selective HDAC8 inhibitors, along with their IC50 values against HDAC8 and other HDACs.</p><p><strong>Methods: </strong>The inhibitors were clustered based on structural symmetry, and common pharmacophores for each cluster were identified using Phase. Molecular docking with all HDACs was performed to determine binding affinity and crucial interacting residues for HDAC8 inhibition. Representative inhibitors from each cluster were subjected to molecular dynamics simulation to analyze RMSD, RMSF, active site amino acid residues, and crucial interacting residues responsible for HDAC8 inhibition. The study reviewed the active site amino acid information, active site cavities of all HDACs, and the basic structure of Zn2+ binding groups.</p><p><strong>Results: </strong>Common pharmacophores identified included AADHR_1, AADDR_1, ADDR_1, ADHHR_1, and AADRR_1. Molecular docking analysis revealed crucial interacting residues: HIS- 142, GLY-151, HIS-143, PHE-152, PHE-20 in the main pocket, and ARG-37, TYR-100, TYR-111, TYR-306 in the secondary pocket. The RMSD of protein and RMSF of active site amino acid residues for stable protein-ligand complexes were less than 2.4 Å and 1.0 Å, respectively, as identified from MD trajectories. The range of Molecular Mechanics Generalized Born Surface Area (MMGBSA) ΔG predicted from MD trajectories was between -15.8379 Å and -61.5017 Å kcal/mol.</p><p><strong>Conclusion: </strong>These findings may expedite the rapid discovery of selective HDAC8 inhibitors subject to experimental evaluation.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748544","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}

{"title":"Efficient Synthesis of Mannopyranoside-based Fatty Acyl Esters: Effects of Acyl Groups on Antimicrobial Potential.","authors":"Md Lutfor Rahaman, Md Atiqur Rahman, Md Mohin Hasnain, Mohammad Amran, Talha Bin Emran, Md Ashikur Rahaman Khan, Md Abdul Majed Patwary, Mohsin Kazi, Mohammed Mahbubul Matin","doi":"10.2174/0115734064292665240523113515","DOIUrl":"https://doi.org/10.2174/0115734064292665240523113515","url":null,"abstract":"<p><strong>Background: </strong>The approval of Sucrose Fatty Acid Esters (SFAEs) as food additives/ preservatives with antimicrobial potential has triggered enormous interest in discovering new biological applications. Accordingly, many researchers reported that SFAEs consist of various sugar moieties, and hydrophobic side chains are highly active against certain fungal species.</p><p><strong>Objective: </strong>This study aimed to conduct aregioselective synthesis of SAFE and check the effect of chain length and site of acylation (i.e., C-6 vs. C-2, C-3, C-4, and long-chain vs. short-chain) on antimicrobial potency.</p><p><strong>Methods: </strong>A direct acylation method maintaining several conditions was used for esterification. In vitro tests, molecular docking, and in silico studies were conducted using standard procedures.</p><p><strong>Results: </strong>In vitro tests revealed that the fatty acid chain length in mannopyranoside esters significantly affects the antifungal activity, where C12 chains are more potent against Aspergillus species. In terms of acylation site, mannopyranoside esters with a C8 chain substituted at the C-6 position are more active in antifungal inhibition. Molecular docking also revealed that these mannopyranoside esters had comparatively better stable binding energy and hence better inhibition, with the fungal enzymes lanosterol 14-alpha-demethylase (3LD6), urate oxidase (1R51), and glucoamylase (1KUL) than the standard antifungal drug fluconazole. Additionally, the thermodynamic, orbital, drug-likeness, and safety profiles of these mannopyranoside esters were calculated and discussed, along with the Structure-Activity Relationships (SAR).</p><p><strong>Conclusion: </strong>This study thus highlights the importance of the acylation site and lipid-like fatty acid chain length that govern the antimicrobial activity of mannopyranoside-based SFAE.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262250","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}

{"title":"In Silico Discovery and Predictive Modeling of Novel Acetylcholinesterase (AChE) Inhibitors for Alzheimer's Treatment.","authors":"Humaera Noor Suha, Md Shamim Hossain, Shofiur Rahman, Abdullah Alodhayb, Md Mainul Hossain, Sarkar M A Kawsar, Raymond Poirier, Kabir M Uddin","doi":"10.2174/0115734064304100240511112619","DOIUrl":"https://doi.org/10.2174/0115734064304100240511112619","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease, akin to coronary artery disease of the heart, is a progressive brain disorder driven by nerve cell damage.</p><p><strong>Method: </strong>This study utilized computational methods to explore 14 anti-acetylcholinesterase (AChE) derivatives (1 ̶ 14) as potential treatments. By scrutinizing their interactions with 11 essential target proteins (AChE, Aβ, BChE, GSK-3β, MAO B, PDE-9, Prion, PSEN-1, sEH, Tau, and TDP-43) and comparing them with established drugs such as donepezil, galantamine, memantine, and rivastigmine, ligand 14 emerged as notable. During molecular dynamics simulations, the protein boasting the strongest bond with the critical 1QTI protein and exceeding drug-likeness criteria also exhibited remarkable stability within the enzyme's pocket across diverse temperatures (300 ̶ 320 K). In addition, we utilized density functional theory (DFT) to compute dipole moments and molecular orbital properties, including assessing the thermodynamic stability of AChE derivatives.</p><p><strong>Result: </strong>This finding suggests a welldefined, potentially therapeutic interaction further supported by theoretical and future in vitro and in vivo investigations.</p><p><strong>Conclusion: </strong>Ligand 14 thus emerges as a promising candidate in the fight against Alzheimer's disease.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158633","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}

{"title":"Substituted 4H-3,1-benzoxazine-4-one Derivatives as Inhibitors of Cathepsin G","authors":"Kholoud F. Aliter, Rami A. Al-Horani","doi":"10.2174/0115734064300678240408084822","DOIUrl":"https://doi.org/10.2174/0115734064300678240408084822","url":null,"abstract":"Background: Cathepsin G (CatG) is a cationic serine protease with a wide substrate specificity. CatG has been reported to play a role in several pathologies, including rheumatoid arthritis, ischemic reperfusion injury, acute respiratory distress syndrome, and cystic fibrosis, among others. Objective: We aim to develop a new class of CatG inhibitors and evaluate their potency and selectivity against a series of serine proteases. Methods: We exploited chemical synthesis as well as chromogenic substrate hydrolysis assays to construct and evaluate the new inhibitors. Results: In this communication, we report on a new class of CatG inhibitors of 4H-3,1-benzoxazin- 4-one derivatives. We constructed a small library of seven substituted 4H-3,1-benzoxazin-4-one derivatives and identified their inhibition potential against CatG. Five molecules were identified as CatG inhibitors with values of 0.84-5.5 μM. Inhibitor 2 was the most potent, with an IC50 of 0.84 ± 0.11 μM and significant selectivity over representative serine proteases of thrombin, factor XIa, factor XIIIa, and kallikrein. Conclusion: Thus, we propose this inhibitor as a lead molecule to guide subsequent efforts to develop clinically relevant potent and selective CatG inhibitors for use as anti-inflammatory agents.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"44 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140811885","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}

{"title":"Synthesis, Molecular Docking Studies and Biological Evaluation of Thiazolyl Hydrazone Derivatives of Chromone-3-carbaldehyde as Potent Anti-Oxidant and Anti-Inflammatory Agents","authors":"Rakhi Gawali, Raghunath Bhosale, Rohit Bavi, Shravan Jadhav, Nargisbano Peerzade","doi":"10.2174/0115734064293848240408085039","DOIUrl":"https://doi.org/10.2174/0115734064293848240408085039","url":null,"abstract":"Introduction: A series of 15 thiazolyl hydrazone derivatives of chromone-3- carbaldehyde have been designed and synthesized by the cyclization of thiosemicarbazone derivatives of chromone-3-carbaldehydes with 4’-substituted-2-bromo acetophenones. Method: All these derivatives were evaluated for antioxidant activity by their direct scavenging activity objects to reactive oxygen species such as DPPH, and nitric oxide, as well as in vitro antiinflammatory activity by a protein denaturation method. Most of these synthesized compounds have shown significant antioxidant activity, among which the compounds 5b, 5c, 5e, 5g, and 5j showed very good antioxidant activities in comparison with the standard ascorbic acid. The in vitro anti-inflammatory activity revealed that the compounds 5b, 5g, and 5h possessed significant activity compared to standard diclofenac sodium. Result: Additionally, molecular docking studies of these molecules using ovalbumin as the protein showed remarkable interactions with its active site residues, and the results indicated that the binding mode of these compounds closely resembled that of the reference compound, diclofenac sodium. Conclusion: Thus, these compounds represent an attractive template for the evaluation of new antiinflammatory and antioxidant agents and might be useful for exploring new therapeutic tools.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"22 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812007","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}

{"title":"Unveiling Therapeutic Avenues for Crohn’s Disease Management: Exploring Inhibitors for Adherent-Invasive Escherichia coli Propanediol Dehydratase","authors":"Mohammed Bourhia, Md. Eram Hosen, Md Omar Faruqe, Faria Tasnim, Mohamed Taibi, Amine Elbouzidi, Yousef A. Bin Jardan, Samir Ibenmoussa, Abdeslam Asehraou","doi":"10.2174/0115734064295521240227052730","DOIUrl":"https://doi.org/10.2174/0115734064295521240227052730","url":null,"abstract":"Introduction:: Inflammatory Bowel Disease (IBD) encompasses a group of chronic disorders distinguished by inflammation of the gastrointestinal tract. Among these, Crohn's Disease (CD) stands out as a complex and impactful condition due to challenges for both diagnosis and management, making it a cynosure of research. Method:: In CD, there is the predominance of proinflammatory bacteria, including the Adherentinvasive Escherichia coli (AIEC) with virulence-associated metabolic enzyme Propanediol Dehydratase (pduC), which has been identified as a therapeutic target for the management of CD. Herein, molecular modeling techniques, including molecular docking, Molecular Mechanics with Generalized Born and Surface Area (MMGBSA), drug-likeness, and pharmacokinetics profiling, were utilized to probe the potentials of eighty antibacterial compounds to serve as inhibitors of pduC. Result:: The results of this study led to the identification of five compounds with promising potentials; the results of the molecular docking simulation revealed the compounds as possessing better binding affinities for the target compared to the standard drug (sulfasalazine), while Lipinski’s rule of five-based assessment of their drug-likeness properties revealed them as potential oral drugs. MMGBSA free energy calculation and Molecular Dynamics (MD) simulation of the complexes formed a sequel to molecular docking, revealing the compounds as stable binders in the active site of the protein. Conclusion:: Ultimately, the results of this study have revealed five compounds to possess the potential to serve as inhibitors of pduC of AIEC. However, experimental studies are still needed to validate the findings of this study.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"49 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140805993","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}

{"title":"Computational Chemistry: Prediction of Compound Accessibility of Targeted Synthesized Compounds","authors":"Visagamoorthy Babu, Sumeer Ahmed, A. K. Rahiman, Sarkar M. A. Kawsar, Malika Berredjem, Ajmal R. Bhat, K. Anver Basha","doi":"10.2174/0115734064293464240405050455","DOIUrl":"https://doi.org/10.2174/0115734064293464240405050455","url":null,"abstract":"Introduction: In the present work, a series of novel pyridine carboxamides 3(a-h) were synthesized and screened with antibacterial activity. This research explores the application of Density Functional Theory (DFT) in studying biological systems at the quantum mechanical level, particularly in the context of drug design. DFT offers a streamlined approach to quantum mechanical calculations, making it indispensable in various scientific fields, and for its exceptional accuracy, reduced computational time, and cost-effectiveness has become a pivotal tool in computational chemistry. This research work highlights the integration of DFT studies with POM analyses, which effectively identify pharmacophoric sites. Moreover, the research incorporates in silico pharmacokinetics analyses to assess the pharmacokinetic properties of synthesized compounds. The paper focused on a series of compounds previously reported, aiming to provide a comprehensive understanding of their electronic structure, pharmacophoric features, and potential as drug candidates. This study not only contributes to the evolving field of computational chemistry but also holds implications for advancing drug design processes by combining theoretical insights with practical analyses. Methods: The compounds 3(a-h) were subjected to Density Functional Theory (DFT) computations using the B3LYP/6-31G(d) basis set to get optimized geometric structures. GaussViewis used to display the contributions of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). The determination of energy gaps was conducted using Gaussian 09W. The pharmacokinetic profiles were evaluated using existing techniques such as Osiris, Petra, and Molinspiration, as well as a novel platform called POM Analyse Results: The computational studies DFT, POM and in silico pharmacokinetics studies revealed that the studied compounds are biologically active, non-toxic, non-carcinogenic in nature and may be utilized as drug candidates. Conclusion: Density functional theory (DFT) investigations emphasize the exceptional stability of complex 3d, which possesses the biggest energy gap and the lowest softness. In contrast, compound 3h demonstrates poorer stability among the tested compounds, characterized by the lowest energy gap and the highest softness values. These findings are further substantiated by absolute energy calculations. The negligible energy difference in compound 3h indicates an increased transfer of electric charge within the molecule, which is associated with its enhanced biological effectiveness. The drug-likeness of the compounds is confirmed by POM and in silico pharmacokinetics investigations, with compound 3h being identified as the most biologically active among the investigated compounds.","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"38 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140623624","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}

{"title":"A Computational Study of Green Tea Extracts and their Derivatives as Potential Inhibitors for Squalene Monooxygenase","authors":"Kabelo Phuti Mokgopa, Kevin A. Lobb, Tendamudzimu Tshiwawa","doi":"10.2174/0115734064280290240211170037","DOIUrl":"https://doi.org/10.2174/0115734064280290240211170037","url":null,"abstract":"Background: According to the World Health Organisation, cardiovascular complications have been recognized as the leading course of death between 2000 and 2019. Cardiovascular complications are caused by excess LDL cholesterol in the body or arteries that can build up to form a plaque. There are drugs currently in clinical use called statins that target HMGCoA reductase. However, these drugs result in several side effects. This work investigated using computational approaches to lower cholesterol by investigating green tea extracts as an inhibitors for squalene monooxygenase (the second-rate-controlling step in cholesterol synthesis). Methods: Pharmacophore modeling was done to identify possible pharmacophoric sites based on the pIC50 values. The best hypothesis generated by pharmacophore modeling was further validated by atom-based 3D QSAR, where 70% of the data set was treated as the training set. Prior molecular docking ADMET studies were done to investigate the physiochemical properties of these molecules. Glide docking was performed, followed by molecular dynamics to evaluate the protein conformational changes. Results: Pharmacophore results suggest that the best molecules to interact with the biological target should have at least one hydrogen acceptor (A5), two hydrogen donors (D9 and D10), and two benzene rings (R14 and R15) for green tea polyphenols and theasinensin A. ADMET result shows that all molecules in this class have low oral adsorption. Molecular docking results showed that some green tea polyphenols have good binding affinities, with most of these structures having a docking score of less than -10 kcal/mol. Molecular dynamics further illustrated that the best-docked ligands perfectly stay within the active site over a 100 ns simulation. Conclusion: The results obtained from this study suggest that green tea polyphenols have the potential for inhibition of squalene monooxygenase, except for theasinensin A","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"92 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140574802","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}