Letters in Drug Design & Discovery最新文献

{"title":"Rings in “Lead-like Drugs”","authors":"Luca Mendes Lampert, Bruno Ruszczyk Machado, Angélica Rocha Joaquim, Fernando Fumagalli","doi":"10.2174/0115701808306429240703100350","DOIUrl":"https://doi.org/10.2174/0115701808306429240703100350","url":null,"abstract":"Background: Lead-like drugs, which present molecular weight (MW) < 300 Da, occupy an important space in the pharmaceutical area. Most of these small molecules have ring systems, which are important for their physicochemical properties and biological activity. Previous studies have evaluated ring systems in historic drugs or drug candidates in clinical trials. Objective: The purpose of this work was to analyze ring systems, focusing on this group of drugs with MW < 300 Da, to obtain specific insights. Methods: The lead-like drugs (n = 219) were obtained from previous publications and the new FDA drug approvals were obtained after that and analyzed using the DataWarrior software. Results: Most of the lead-like drugs (> 92%) present one or two rings, with the benzene ring and heterocycle ring systems being predominant. Pyridine, imidazole, piperidine, 4,5-dihydro-1Himidazole, and indole are the most frequent heterocycles in this set. The higher frequency of the 4,5- dihydro-1H-imidazole ring in the lead-like drugs is worth noting, as it is not observed in other drugs. The introduction of new rings has been similar in the lead-like drugs and the historic drugs, over the years; an example would be the 1,2,4-thiadiazinane 1,1-dioxide, which is present in the antimicrobial Taurolidine, a lead-like drug, and engages in the metabolic activation of the drug. Conclusion: In general, the ring systems in the lead-like drugs appear to follow similar patterns to the historic drugs. Additionally, few new ring systems are being introduced, which suggests that this is an emergent field to be explored in drug discovery.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141585552","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":"Herbal and Dietary supplements for Hypertension Management.","authors":"Mounia Driouech, Mounime Kadi, Abderrahim Ziyyat, Hassane Mekhfi, Mohamed Bnouham, Abdelkhaleq Legssyer","doi":"10.2174/0115701808297606240628065101","DOIUrl":"https://doi.org/10.2174/0115701808297606240628065101","url":null,"abstract":": Herbal and dietary supplements are products that add more nutritional value to the diet. The use of these products has increased worldwide and has become widespread. Recently, the food products market has witnessed significant advancements in improving the health and well-being of individuals with increased nutritional requirements or in preventing related diseases and issues. Overall, dietary supplements possess pharmacological properties that are not crucial for disease control, such as high blood pressure but are essential for various physiological processes. To report the recent pre-clinically and clinically proven benefits of different hypertension treatments, an extensive literature search was conducted using widely available scientific databases of oral supplements. This review aims to raise awareness about commonly used dietary and herbal products, particularly among individuals with high blood pressure. Additionally, this paper highlights several nutritional supplements that hold promise for future research.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141585451","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":"Molecular Dynamics Simulations and Binding Free Energy Calculations to Discover New Insights into NLRP3 Inhibitors","authors":"Karla Joane da Silva Menezes, Fernanda De França Genuíno Ramos Campos, Marianny de Souza, Daniel Calazans Medeiros, Igor José dos Santos Nascimento, Ricardo Olimpio de Moura","doi":"10.2174/0115701808303890240620074039","DOIUrl":"https://doi.org/10.2174/0115701808303890240620074039","url":null,"abstract":"Background: Inflammation is an immunological reaction against an aggressor agent. NLRP3 inflammasome is a component of the immune system, which, when excessively activated, results in several inflammatory diseases, making it an attractive target for discovering antiinflammatory drugs. Computer-Aided Drug Design (CADD) techniques are powerful tools used to search for new drugs in less time and financial cost. Recently, studies demonstrated the CADD methods to discover information about NLRP3 inhibitors MCC950 and NP3-146. In addition, the discovery of GDC-2394 and its evaluation in clinical trials instigate new studies to find binding modes and structural attributes that can used in drug design works against this target. Objectives: Here, molecular modeling methods were used to discover the significant interactions of GDC-2394, MCC950, and NP3-146 with NLRP3 to obtain helpful information in drug design compared to other inhibitors. Methods: Molecular docking was performed using GOLD software. The best complexes were submitted into molecular dynamics simulations using GROMACS software, and the MM-PBSA was used to provide the free binding energy, which was performed using the tool g_mmpbsa compiled in GROMACS. Results: The RMSD, RMSF, Rg, SASA, and H-bond plots showed that the compound was stable during MD simulation time (100 ns) for GDC-2394. The PCA analysis for all compounds verified similar variance of the complex with the inhibitors to the apo-NLRP3, indicative of stability. DCCM analysis showed the best correlation in residues 134 - 371 region, which contains critical amino acids from the binding site (Ala227, Ala228, and Arg578), besides the newly identified residues. Using MMPBSA to provide the binding free energy, it was observed that the high affinity of the drugs against NLRP3 is related to the lower rigidity of the structure. Furthermore, we identified the critical residues Phe575, Pro352, Tyr632, and Met661 related to the coupling process. result: Then, RMSD, RMSF, Rg, SASA, and H-bond plots showed that the compound was stable during MD simulation time (100 ns) for GDC-2394. The PCA analysis for all compounds verified similar variance of the complex with the inhibitors to the apo-NLRP3, indicative of stability. Through DCCM analysis, the best correlation was observed in residues 134 - 371 region, which contains critical amino acids from the binding site (Ala227, Ala228, and Arg578), besides the newly identified residues. Using MM-PBSA to provide the binding free energy, it was observed that the high affinity of the drugs against NLRP3 is related to the lower rigidity of the structure. Furthermore, we identified the critical residues Phe575, Pro352, Tyr632, and Met661 related to the coupling process. Conclusion: Thus, these discoveries may contribute to the development of new anti-inflammatory drugs, such as NLRP3 inhibitors.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141530637","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":"The Hepatoprotective Effect of a Newly Synthesized 5-Mercapto-1,2,4-Triazole Derivative based on Nalidixic Acid Against Ccl4 induced Oxidative Stress in Mice","authors":"Ibrahim Mhaidat, lena tahat, Ghada Alomari, Laiali AL-Quraan, Abeer Gharaibeh, Bahaa Al-Trad","doi":"10.2174/0115701808294306240613104855","DOIUrl":"https://doi.org/10.2174/0115701808294306240613104855","url":null,"abstract":"Background: Oxidative stress plays a key role in the development of a wide range of diseases, including diabetes and cancer. Recent studies reported that the derivatives of triazole compounds have a potent antioxidant activity. Therefore, this study was designed to investigate the hepatoprotective effect of a novel newly synthesized 5-mercapto-1,2,4-triazole based on nalidixic acid [1-ethyl-3-(5-mercapto-4-(p-tolyl)-4H-1,2,4-triazol-3-yl)-7-methyl-1,8-naphthyridin] (MTTN) 3 compound against CCl4 induced oxidative stress in mice. Materials and Methods: The MTTN compound was synthesized through the interaction and then cyclization of p-tolylisothiocyanate with nalidixic acid hydrazide. By using 1 H-NMR, 13C-NMR, IR, and elemental analyses, the structure of the newly synthesized MTTN compound was identified. To investigate the hepatoprotective effect of this compound, forty BALB/c mice were divided into four groups (n=10) as follows: the control group, the oxidative stress-induced group, which was intraperitoneally injected with 10% CCl4 (2 mL/kg), one pre-treatment group, which was treated orally with 200 mg/kg of MTTN compound for 8 days before being treated with CCl4 at day 8, and one post-treatment group, which was treated orally with 200 mg/kg of MTTN compound for 8 days simultaneously with CCl4 co-administration at days 3 and 5. At day 9, animals were scarified and serum and liver samples were collected. Results: CCl4 administration caused significant hepatotoxicity as evidenced by marked elevation in the serum activity of the liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and high blood cholesterol levels. Furthermore, the hepatic malondialdehyde (MDA) level, a marker of lipid peroxidation, was increased with CCl4 administration that was associated with a decrease in the hepatic superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.05). However, pre and post-treatment with the new newly synthesized MTTN compound significantly reduced the serum levels of AST, ALT, and cholesterol and reduced hepatic oxidative stress as indicated by the decrease in the hepatic MDA level and the increases in the SOD and CAT activities (p < 0.05). Conclusion: This study suggests that the newly synthesized MTTN compound has a potent antioxidant property and can protect against CCl4-induced liver injury. Thus, with more clinical studies, this compound may be used as effective therapeutic agents against oxidative stress related diseases.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141503740","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, Characterization, Antibacterial Evaluation, and Enzyme Inhibition Activity of a Novel Nitrogen-containing Heterocyclic Sulfonamide","authors":"Jingyao Kong, Xue Zhang, Guangshan Xuan","doi":"10.2174/0115701808308364240422131751","DOIUrl":"https://doi.org/10.2174/0115701808308364240422131751","url":null,"abstract":"aims: Synthesis and screening of some novel sulfonamide derivatives with antibacterial and enzyme inhibitory effects. background: Currently, microbial infections are a global threat to human health and there is an urgent need to develop new and effective antimicrobial drugs to treat microbial infections. Carbonic anhydrase II is associated with a variety of diseases in vivo, and the development of carbonic anhydrase II inhibitors has far-reaching implications for the treatment of a wide range of diseases. objective: Synthesis of some novel sulfonamide derivatives containing pyrazole, 1,2,3-triazole and investigation of antimicrobial and enzyme inhibitory activities of the synthesised compounds. method: The compounds with bacteriostatic effect were screened by using the ring of inhibition method and MTT chromogenic method, and the mechanism of bacteriostatic inhibition and description of bacteriostatic effect of the synthesized compounds were investigated with the aid of MOE molecular docking simulation and Gaussian molecular weighting calculations. The in vitro inhibitory effect of the synthesized compounds on COX-2 was studied by phenylmethyl acetate colour development method. result: The results of bacterial inhibition experiments revealed that compounds 11d and 11e had better inhibition effects on pathogenic bacteria, especially on Candida albicans, which was essentially the same as that of the positive control FLUCZ. The compounds 4f, 7b and 11c were found to have the best inhibitory effect by COX-2 in vitro inhibition experiments, especially 11c, which had a better inhibitory effect than the positive control acetazolamide. conclusion: A series of derivatives obtained by introducing pyrazole and 1,2,3-triazole rings into sulfonamides have good bacteriostatic and COX-2 inhibition effects, and have the potential to be developed as novel antimicrobial agents and enzyme inhibitors. other: None other","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141192197","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":"Electrochemical Modification of Metronidazole and its Application as Antibacterial and Potential Drug Agent","authors":"Samuel Attah Egu, Sunday Okpanachi Idih, Favour Idih, Ruth Foluke Aminu, Lawrence Achimugu, Aminu Omale, Jamila Audu Omale, Lian Ojotule Abah, Emmanuel Amlabu","doi":"10.2174/0115701808281133240424055511","DOIUrl":"https://doi.org/10.2174/0115701808281133240424055511","url":null,"abstract":"Background: Drug resistance poses a threat to global health given the disturbing rate at which microbiological illnesses are rising and the widespread use of antibiotics. While naturally occurring antibiotics reduce the likelihood of bacterial resistance, recognized drugs can develop the same properties when structurally modified. Metronidazole has been targeted to achieve this feat. Objective: The purpose of this work is to enable the structural modification of metronidazole by means of electric current, using inexpensive, easily accessible magnesium ribbon as electrodes in order to produce a novel, effective antibiotic. Method: With magnesium ribbon electrodes, metronidazole is modified electrochemically, in an undivided cell system. Ultraviolet-visible (UV-Vis), Fourier Transform Infrared (FTIR), and Gas Chromatography-Mass Spectrometry (GC-MS) were used to characterize the product. Antibacterial activity was evaluated using the agar well diffusion method and Wistar rats were used for in vivo toxicity assessment. Result: 2-Methyl-1-vinyl-1H-imidazol-5-amine showed good antibacterial activities compared to the standard nitrofurantoin and toxicity evaluations using Wistar rats revealed that the product might induce dose-dependent variations in kidney function biomarkers, with doses of 100 mg/kg and below. However, when the compound was administered orally, there was no significant effect on liver function, even at a dose of 1000 mg/kg. Conclusion: These results point to the modified metronidazole's potential as a potent antibiotic with controllable toxicity, indicating that additional research into its pharmacological uses is necessary.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840003","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":"Preparation and Physicochemical Properties of a Thermosensitive Hydrogel-based Lipopeptide Biosurfactant","authors":"Sepehr Afsharipour, Mohammad Amin Raeisi Estabragh, Amirhossein Namaki, Mandana Ohadi, Mohammad Hassan Moshafi, Ibrahim M. Banat, Gholamreza Dehghannoudeh","doi":"10.2174/0115701808296878240419065845","DOIUrl":"https://doi.org/10.2174/0115701808296878240419065845","url":null,"abstract":"Background: Temperature-sensitive (thermo-sensitive) formulations are a novel drug delivery dosage form that shows bio-inspired behavior in various applications. The structure and properties of a thermosensitive polymer are critical in designing an intelligent biometric polymer that contains lipopeptide biosurfactants. Objectives: In this study, thermo-sensitive hydrogels with lipopeptide biosurfactants as a potential wound dressing dosage form were formulated and examined regarding physicochemical properties. Methods: The lipopeptide biosurfactants were isolated from the Acinetobacter junni B6 bacterial strain and loaded on a formulation of poloxamer 407® and carboxymethyl cellulose as a gelling agent. Numerous experiments were carried out to evaluate the physicochemical properties of these formulations, such as the stability, spreadability, release profile, and kinetic. Results: The formulation (Poloxamer 407® (19% w/v), carboxymethyl cellulose (2% w/v), lipopeptide biosurfactants (5mg/mL), benzyl alcohol (1% v/v), and 0.1mL polyethylene glycol 400) was select as the optimum formulation. The selected formulation released 26.9% of the lipopeptide biosurfactants with anomalous transport kinetics after 10 hours. Conclusions: The results showed that a thermo-sensitive formulation could help achieve a sustained release of lipopeptide biosurfactants and potentially be used as a dressing formulation for wounds in future studies.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140839776","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":"Structural Insights into Mouse β3-Adrenergic Receptor: A Promising Target for Obesity and Diabetes Therapeutics","authors":"Vijayalakshmi Gangadhara, Kavishankar Gawli, Asha Abraham","doi":"10.2174/0115701808301580240405071948","DOIUrl":"https://doi.org/10.2174/0115701808301580240405071948","url":null,"abstract":"Background:: Investigating the structural attributes of the murine beta3-adrenergic receptor (β3-AR) is imperative for comprehending metabolic regulation, given its close resemblance to the human β3-AR. This receptor holds promise as a target for novel drug development against obesity and diabetes. Despite its potential, the absence of knowledge regarding the structure of murine β3- AR hampers a comprehensive understanding of its functionality. Objective:: Our study aimed to model the three-dimensional (3D) structure of murine β3-AR through various molecular structure prediction and simulation techniques, thus addressing the existing gap in structural information. Methods:: Employing diverse structure prediction programs, we refined the predicted structure of murine β3-AR. Primary sequence analysis offered insights into charge distribution, stability, and hydrophobic properties. The binding sites were identified in the modeled structure. Molecular Dynamics (MD) simulation provided the structural stability and dynamic behavior of the predicted β3- AR structure. Results:: The β3-AR protein exhibited specific characteristics, including a pI of 9.57, an aliphatic index of 98.35, a GRAVY score of 0.289, and the presence of conserved motifs and disulfide linkages. Utilizing the programs such as Phyre2, Swissmodel, I-Tasser, and AlphaFold2, we generated a 3D model of murine β3-AR. Subsequent refinement using ModRefiner revealed a structure comprising 13 helices, 2 strands, and 21 turns. The Ramachandran plot indicated favorable regions for 93.2% of residues, with minimal deviations. A 50 ns MD simulation demonstrated the consistent stability and integrity of the β3-AR protein. The top three binding pockets were identified based on varying areas and volumes. Dynamic behavior within residues Ser 252 and Arg 253 was observed, indicating flexibility in conformation. This study marks the first-ever exploration, offering initial structural insights into murine β3-AR. Conclusion:: This study underscores the critical role of computational approaches in predicting the 3D structure of β3-AR. We derived a refined model by employing diverse prediction techniques, elucidating key features. The findings emphasize the significance of this methodology in comprehending the structural foundation of β3-AR, providing valuable insights for targeted medication development against conditions such as obesity and diabetes.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628885","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":"Effects of Compound in Hedyotis diffusa Willd against Acute Myeloid Leukemia: An In silico and In vitro Study","authors":"Chunyi Lyu, Xuewei Yin, Zonghong Li, Teng Wang, Ruirong Xu","doi":"10.2174/0115701808287616240321080922","DOIUrl":"https://doi.org/10.2174/0115701808287616240321080922","url":null,"abstract":"Background: Hedyotis diffusa Willd (HDW) is an herb that has been used empirically for treating cancer, and its antileukemic effect has been confirmed by laboratory evidence. This study aimed to explore the underlying mechanism by which HDW and its active compound exert effects on acute myeloid leukemia (AML) through in silico analyses combined with experimental validation. Methods: The targets of the compounds were collected from the database and intersected with AML targets. Based on these data, a protein-protein interaction (PPI) network and compound-target (C-T) network were constructed, and KEGG enrichment analysis was performed. Topological analysis of the C-T network and PPI network was performed to screen for hub compounds and targets. Molecular dynamics simulations were conducted to test the binding mode and strength between the targets and the compounds at the molecular level. Cell viability, flow cytometry, ELISA, and Q-PCR were further used to evaluate the in silico results. Results: A total of 86 targets of 12 screened active compounds of HDW against AML were identified. According to topological analysis, tumor protein p53 (TP53) and signal transducer and activator of transcription 3 (STAT3) exhibited the highest degree of centrality (DC) in the PPI networks of HDW targets. Quercetin had a higher affinity for TP53 than for STAT3. Molecular dynamics simulations confirmed that the TP53-quercetin docked complex was stable with respect to the original TP53-ligand complex. The targets of HDW and quercetin against AML were significantly enriched in multiple biological processes, including the p53 signaling pathway and apoptosis. The results from the in vitro experiment confirmed that quercetin triggers apoptosis in the human AML cell line KG-1 through the p53 pathway protein. Conclusion: This study outlines the multi-compound, multi-target, and multi-pathway mechanism by which HDW affects AML based on an in silico predictive model and further validates the antileukemic mechanism of the screened active compound in an in vitro model. This study provides a perspective for studying the antileukemic mechanism of HDW for further research.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140615510","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":"Design, Synthesis, and In vitro Biological Activities of Matrine Skeleton Derivatives as Potential Cancer Inhibitors","authors":"Bin Zhou, Lisheng Wang, Yongquan Wei, Meiyan Jiang, Xingdong Wang","doi":"10.2174/0115701808300981240408063655","DOIUrl":"https://doi.org/10.2174/0115701808300981240408063655","url":null,"abstract":"Background: Thirteen derivatives were designed and synthesized based on the excellent lead compound Matrine. Objective: This study aimed to discover novel anticancer agents with superior anticancer activity and to support the discovery of new drugs. Methods: The in vitro antiproliferative activity of all derivatives against four human cancer cells, A549, HGC-27, HCT-116, and HeLa, was determined by MTT. The best active compounds were subjected to cell cloning, migration, cell cycle and apoptosis, and molecular docking. Results: Compound 5XI showed the best activity against all four cell lines, especially against A549 cells, with an IC50 of 5.805 μmol/L. The antiproliferative activity of 5XI was much higher than that of matrine and only slightly weaker than that of Cisplatin, a multi-targeted small molecule inhibitor. 5XI also showed excellent inhibitory activity in cell cycle, apoptosis, cell scratch, and cell cloning assays and has shown good affinity in docking studies. Conclusion: 5XI has excellent antiproliferative activity, significantly inhibits cell cloning and migration, affects cancer cell cycle distribution, and induces apoptosis in a concentration-dependent manner, making it a potential anticancer drug agent.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617848","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}