Molecular Diversity最新文献_第8页

Natural product-derived ALK inhibitors for treating ALK-driven lung cancers: an in silico study. 用于治疗 ALK 驱动型肺癌的天然产物衍生 ALK 抑制剂：一项硅学研究。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-08-08 DOI: 10.1007/s11030-024-10953-2

Saud O Alshammari, Qamar A Alshammari

{"title":"Natural product-derived ALK inhibitors for treating ALK-driven lung cancers: an in silico study.","authors":"Saud O Alshammari, Qamar A Alshammari","doi":"10.1007/s11030-024-10953-2","DOIUrl":"https://doi.org/10.1007/s11030-024-10953-2","url":null,"abstract":"Anaplastic lymphoma kinase (ALK)-driven lung cancer represents a critical therapeutic target, demanding innovative approaches for the identification of effective inhibitors. Anaplastic lymphoma kinase (ALK), a key protein involved in the pathogenesis of ALK-driven lung cancers, has been the focus of extensive drug discovery efforts. This study employed a comprehensive computational drug discovery approach, integrating virtual screening with the Lipinski filter, re-docking, molecular dynamics (MD) simulations, and free energy calculations to identify potential inhibitors from a natural compound library. Utilizing the MTiOpenScreen web server, we screened for compounds that exhibit favorable interactions with ALK, resulting in 1227 compounds with virtual screening scores ranging from - 10.2 to - 3.7 kcal/mol. Subsequent re-docking of three selected compounds (ZINC000059779788, ZINC000043552589, and ZINC000003594862) and one reference compound against ALK yielded docking scores - 10.4, - 10.2, - 10.2, and - 10.1 kcal/mol, respectively. These compounds demonstrated promising interactions with ALK, suggesting potential inhibitory effects. Advanced analyses, including MD simulation and binding free energy calculations, further supported the potential efficacy of these compounds. MD simulations, particularly the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses, revealed that compounds ZINC000059779788 and ZINC000003594862 achieved better stability compared to compound ZINC000043552589. These stable conformations suggest effective binding over time. Free energy calculations using the MM/GBSA method showed that ZINC000059779788 had the most favorable binding energy, indicating a strong and stable interaction with the ALK protein. The promising computational findings from this study emphasize the necessity for additional experimental testing to verify the therapeutic efficacy of these natural compounds for treating lung cancers.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of novel 4-substituted isatin Schiff base derivatives as potential autophagy inducers and evaluation of their antitumour activity. 合成新型 4-取代靛红席夫碱衍生物作为潜在的自噬诱导剂并评估其抗肿瘤活性。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-08-07 DOI: 10.1007/s11030-024-10954-1

Huayuan Tan, Guanglong Zhang, Chenlu Xu, Xue Lei, Jiayi Chen, Haitao Long, Xuemei Qiu, Wenhang Wang, Yue Zhou, Danping Chen, Chengpeng Li, Zhurui Li, Zhenchao Wang

{"title":"Synthesis of novel 4-substituted isatin Schiff base derivatives as potential autophagy inducers and evaluation of their antitumour activity.","authors":"Huayuan Tan, Guanglong Zhang, Chenlu Xu, Xue Lei, Jiayi Chen, Haitao Long, Xuemei Qiu, Wenhang Wang, Yue Zhou, Danping Chen, Chengpeng Li, Zhurui Li, Zhenchao Wang","doi":"10.1007/s11030-024-10954-1","DOIUrl":"https://doi.org/10.1007/s11030-024-10954-1","url":null,"abstract":"Induction of autophagic death in cancer cells is one of the promising strategies for the development of anti-cancer therapeutics. In the present study, we designed and synthesized a series of isatin Schiff base derivatives containing thioether structures. After discovering the highly active target compound H13 (IC50 = 4.83 μM) based on in vitro antiproliferation, we also found it had a high safety against normal cells HEK293 with CC50 of 69.01 μM, indicating a sufficient therapeutic window. In addition, to provide reference for subsequent studies, a model was successfully constructed by Sybyl software. Preliminary mechanistic studies suggested that H13-induced apoptosis may be closely related to ROS accumulation and mitochondrial dysfunction. Subsequent studies revealed that H13 inhibited cell proliferation by inducing cellular autophagy mainly through blocking signal of the PI3K/AKT/mTOR pathway. Altogether, these results suggested that H13 was potentially valuable as a lead compound.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent developments in the design of functional derivatives of edaravone and exploration of their antioxidant activities. 依达拉奉功能衍生物设计及其抗氧化活性探索的最新进展。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-08-05 DOI: 10.1007/s11030-024-10940-7

R Divya Mohan, Naveen V Kulkarni

引用次数: 0

Application progress of deep generative models in de novo drug design 深度生成模型在新药设计中的应用进展。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-08-04 DOI: 10.1007/s11030-024-10942-5

Yingxu Liu, Chengcheng Xu, Xinyi Yang, Yanmin Zhang, Yadong Chen, Haichun Liu

引用次数: 0

Suppressing Mycobacterium tuberculosis virulence and drug resistance by targeting Eis protein through computational drug discovery 通过计算药物发现靶向 Eis 蛋白抑制结核分枝杆菌的毒力和耐药性

IF 3.8 2区化学

Molecular Diversity Pub Date : 2024-08-03 DOI: 10.1007/s11030-024-10946-1

Geethu S. Kumar, Amaresh Kumar Sahoo, Nishant Ranjan, Vivek Dhar Dwivedi, Sharad Agrawal

{"title":"Suppressing Mycobacterium tuberculosis virulence and drug resistance by targeting Eis protein through computational drug discovery","authors":"Geethu S. Kumar, Amaresh Kumar Sahoo, Nishant Ranjan, Vivek Dhar Dwivedi, Sharad Agrawal","doi":"10.1007/s11030-024-10946-1","DOIUrl":"https://doi.org/10.1007/s11030-024-10946-1","url":null,"abstract":"Tuberculosis (TB) remains a critical health threat, particularly with the emergence of multidrug-resistant strains. This demands attention from scientific communities and healthcare professionals worldwide to develop effective treatments. The enhanced intracellular survival (Eis) protein is an acetyltransferase enzyme of Mycobacterium tuberculosis that functions by adding acetyl groups to aminoglycoside antibiotics, which interferes with their ability to bind to the bacterial ribosome, thereby preventing them from inhibiting protein synthesis and killing the bacterium. Therefore, targeting this protein accelerates the chance of restoring the aminoglycoside drug activity, thereby reducing the emergence of drug-resistant TB. For this, we have screened 406,747 natural compounds from the Coconut database against Eis protein. Based on MM/GBSA rescoring binding energy, the top 5 most prominent natural compounds, viz. CNP0187003 (− 96.14 kcal/mol), CNP0176690 (− 93.79 kcal/mol), CNP0136537 (− 92.31 kcal/mol), CNP0398701 (− 91.96 kcal/mol), and CNP0043390 (− 91.60 kcal/mol) were selected. These compounds exhibited the presence of a substantial number of hydrogen bonds and other significant interactions confirming their strong binding affinity with the Eis protein during the docking process. Subsequently, the MD simulation of these compounds exhibited that the Eis-CNP0043390 complex was the most stable, followed by Eis-CNP0187003 and Eis-CNP0176690 complex, further verified by binding free energy calculation, principal component analysis (PCA), and Free energy landscape analysis. These compounds demonstrated the most favourable results in all parameters utilised for this investigation and may have the potential to inhibit the Eis protein. There these findings will leverage computational techniques to identify and develop a natural compound inhibitor as an alternative for drug-resistant TB.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141883484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel quinolone substituted 1,3,4-oxadiazole derivatives: design, synthesis, antimicrobial and anti-inflammatory potential. 新型喹诺酮取代的 1,3,4-恶二唑衍生物：设计、合成、抗菌和消炎潜力。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-08-03 DOI: 10.1007/s11030-024-10949-y

Vishal Sharma, Rina Das, Dinesh Kumar Mehta, Diksha Sharma

{"title":"Novel quinolone substituted 1,3,4-oxadiazole derivatives: design, synthesis, antimicrobial and anti-inflammatory potential.","authors":"Vishal Sharma, Rina Das, Dinesh Kumar Mehta, Diksha Sharma","doi":"10.1007/s11030-024-10949-y","DOIUrl":"https://doi.org/10.1007/s11030-024-10949-y","url":null,"abstract":"A novel series of quinolone-substituted 1,3,4-oxadiazole derivatives 4(a-l) have been designed and synthesized. The target compounds were investigated for their antibacterial activity against gram positive (Staphylococcus aureus, ATCC 25923, Enterococcus faecalis, ATCC 29212) and gram negative bacterium (Escherichia coli, ATCC 25922, Pseudomonas aeruginosa, ATCC 27853) for antifungal activity using (Candida albicans, ATCC 10231) and anti-inflammatory activity as COX-II inhibitors, respectively. The 1,3,4-oxadiazole functionality was introduced at C-6 position of pipemidic acid derivatives. IR, 1H NMR and Mass spectrometry techniques confirmed the structure of synthesized derivatives. The quinolone (pipemidic acid)-oxadiazole hybrid derivatives were effective against bacterial strains. When compared to ciprofloxacin (MIC 16 µg/mL), the compounds under consideration (4f, 4h, and 4k) showed significant antibacterial activity against all bacterial strains except Enterococcus faecalis, with MICs of 8 µg/mL. On the other hand, synthesized target compounds 4(a-l) did not respond well against Candida albicans fungal strain. The compound (4k) represents high % inhibition against COX-II. The compounds (4f, 4h and 4k) exhibited highest hydrogen bonding interaction with ARG57, ARG72, ARG78, LEU54 and MET16 target residues with a binding energy of - 8.4, - 8.6 and - 8.5 kcal/mol into the active pocket of DNA gyrase enzyme respectively even better in comparison to reference ligands. Based on the docking study, quinolone (pipemidic acid) oxadiazole hybrid structural ligands exhibited strong interaction at binding pockets of DNA gyrase enzyme.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MolGC: molecular geometry comparator algorithm for bond length mean absolute error computation on molecules MolGC：用于计算分子键长平均绝对误差的分子几何比较器算法。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-08-03 DOI: 10.1007/s11030-024-10945-2

Javier Camarillo-Cisneros, Graciela Ramirez-Alonso, Carlos Arzate-Quintana, Hugo Varela-Rodríguez, Abimael Guzman-Pando

{"title":"MolGC: molecular geometry comparator algorithm for bond length mean absolute error computation on molecules","authors":"Javier Camarillo-Cisneros, Graciela Ramirez-Alonso, Carlos Arzate-Quintana, Hugo Varela-Rodríguez, Abimael Guzman-Pando","doi":"10.1007/s11030-024-10945-2","DOIUrl":"10.1007/s11030-024-10945-2","url":null,"abstract":"<div>Density Functional Theory (DFT) is extensively used in theoretical and computational chemistry to study molecular and crystal properties across diverse fields, including quantum chemistry, materials physics, catalysis, biochemistry, and surface science. Despite advances in DFT hardware and software for optimized geometries, achieving consensus in molecular structure comparisons with experimental counterparts remains a challenge. This difficulty is exacerbated by the lack of automated bond length comparison tools, resulting in labor-intensive and error-prone manual processes. To address these challenges, we propose MolGC, a Molecular Geometry Comparator algorithm that automates the comparison of optimized geometries from different theoretical levels. MolGC calculates the mean absolute error (MAE) of bond lengths by integrating data from various DFT software. It provides interactive and customizable visualization of geometries, enabling users to explore different views for enhanced analysis. In addition, it saves MAE computations for further analysis and offers a comprehensive statistical summary of the results. MolGC effectively addresses complex graph labeling challenges, ensuring accurate identification and categorization of bonds in diverse chemical structures. It achieves a 98.91% average rate in correct bond label assignments on an antibiotics dataset, showcasing its effectiveness for comparing molecular bond lengths across geometries of varying complexity and size. The executable file and software resources for running MolGC can be downloaded from https://github.com/AbimaelGP/MolGC/tree/main.\u0000</div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

You must be flexible enough to be trained, Mr. Dynamics simulator. 你必须有足够的灵活性来接受训练，动力模拟器先生。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-08-01 Epub Date: 2023-07-12 DOI: 10.1007/s11030-023-10689-5

Ammar Usman Danazumi, Haruna Isiyaku Umar

引用次数: 0

Synthesis, anti-microbial, and docking studies of functionalized chromenyl phosphonates using ionic liquid catalyst. 利用离子液体催化剂合成、抗微生物和对接研究功能化铬酰基膦酸盐。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-07-31 DOI: 10.1007/s11030-024-10941-6

Sowjanya Bandlapalli, Reddi Mohan Naidu Kalla, Venkata Narayana Palakollu, Gouthami Kuruvalli, Vaddi Damodara Reddy, Kholood A Dahlous, Jaewoong Lee

{"title":"Synthesis, anti-microbial, and docking studies of functionalized chromenyl phosphonates using ionic liquid catalyst.","authors":"Sowjanya Bandlapalli, Reddi Mohan Naidu Kalla, Venkata Narayana Palakollu, Gouthami Kuruvalli, Vaddi Damodara Reddy, Kholood A Dahlous, Jaewoong Lee","doi":"10.1007/s11030-024-10941-6","DOIUrl":"https://doi.org/10.1007/s11030-024-10941-6","url":null,"abstract":"Synthesis of functionalized chromenyl phosphonates by the reaction among 2-hydorxybenzaldehydes, dicyanoethane, and dialkyl phosphonates that was promoted by choline hydroxide ionic liquid catalyzes the simultaneous, Knoevenagel, Pinner, and phospha-Michael reactions, under neat condition at room temperature. Important phosphorus-containing compounds can be produced at a reasonable cost because of the mild reaction conditions and the inexpensive promoter choline hydroxide. Furthermore, the desired products can be obtained without the need for any extraction or chromatography steps. An alternate technique for the simple and high-yield synthesis of functionalized chromenyl phosphonates is offered by this protocol. The synthesized compounds were studied by anti-microbial activity and docking studies. The title compounds molecular docking investigations demonstrated their efficacy as therapeutic agents against DNA Gyrase B and Aspergillus niger endoglucanase in both antibacterial and antifungal inhibition, and they identified compounds 4a, 4d, 4l, 4p, and 4q as promising candidates for microbial treatment, with binding affinities ranging from - 6.9 to - 7.4 kcal/mol.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Scaffolds imparting anthelmintic activity: recent advancements and SAR studies. 具有驱虫活性的支架：最新进展和 SAR 研究。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-07-31 DOI: 10.1007/s11030-024-10869-x

Pawan Kumar, Rohit Bhatia, Naresh Kumar Rangra

{"title":"Scaffolds imparting anthelmintic activity: recent advancements and SAR studies.","authors":"Pawan Kumar, Rohit Bhatia, Naresh Kumar Rangra","doi":"10.1007/s11030-024-10869-x","DOIUrl":"https://doi.org/10.1007/s11030-024-10869-x","url":null,"abstract":"Helminthiasis, affecting billions globally, poses a significant health concern, especially in impoverished regions with inadequate sanitation. The intricate anatomical complexity of helminths requires specialized treatment approaches. There is currently no effective vaccine against helminth infections. Anthelmintics, crucial for combating these infections, target neuromuscular functions in parasites without harming the host. However, the emergence of resistance to existing anthelmintics, notably benzimidazoles, presents a growing global challenge. This review delves into the structure-activity relationship of previously synthesized core anthelmintic scaffolds-Benzimidazole, coumarin, pyrazoline, triazole, and others-to elucidate their promising anthelmintic activities. Understanding the structure-activity relationship of these novel benzimidazole derivatives, Coumarin derivatives, and others is crucial in designing potent anthelmintics, overcoming resistance, and optimizing efficacy to combat the escalating global burden of helminth infections. In the present review, we cover recently studied compounds (from the year 2019 to till date) which have promising anthelmintic activity. This review will be useful for the pharmacology and medicinal chemistry researchers working in the area anthelmintics with various scaffolds like aminobenzothiazole, benzimidazole, benzothiazole, coumarin, chromene, spiroketal, pyrazoline, triazole, etc. to design novel potent anthelmintic compound.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0