Molecular Diversity最新文献_第8页

Destabilisation of Alzheimer's amyloid-β protofibrils by Baicalein: mechanistic insights from all-atom molecular dynamics simulations. 黄芩素对阿尔茨海默氏症淀粉样蛋白-β原纤维的脱稳作用：全原子分子动力学模拟的机理启示。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-08 DOI: 10.1007/s11030-024-11001-9

Sadika Choudhury, Ashok Kumar Dasmahapatra

{"title":"Destabilisation of Alzheimer's amyloid-β protofibrils by Baicalein: mechanistic insights from all-atom molecular dynamics simulations.","authors":"Sadika Choudhury, Ashok Kumar Dasmahapatra","doi":"10.1007/s11030-024-11001-9","DOIUrl":"https://doi.org/10.1007/s11030-024-11001-9","url":null,"abstract":"Alzheimer's disease (AD) is the most common form of dementia and the fifth leading cause of death globally. Aggregation and deposition of neurotoxic Aβ fibrils in the neural tissues of the brain is a key hallmark in AD pathogenesis. Destabilisation studies of the amyloid-peptide by various natural molecules are highly relevant due to their neuroprotective and therapeutic potential for AD. We performed molecular dynamics (MD) simulation to investigate the destabilisation mechanism of amyloidogenic protofilament intermediate by Baicalein (BCL), a naturally occurring flavonoid. We found that the BCL molecule formed strong hydrophobic contacts with non-polar residues, specifically F19, A21, V24, and I32 of Chain A and B of the pentameric protofibril. Upon binding, it competed with the native hydrophobic contacts of the Aβ protein. BCL loosened the tight packing of the hydrophobic core by disrupting the hydrogen bonds and the prominent D23-K28 inter-chain salt bridges of the protofibril. The decrease in the structural stability of Aβ protofibrils was confirmed by the increased RMSD, radius of gyration, solvent accessible surface area (SASA), and reduced β-sheet content. PCA indicated that the presence of the BCL molecule intensified protofibril motions, particularly affecting residues in Chain A and B regions. Our findings propose that BCL would be a potent destabiliser of Aβ protofilament, and may be considered as a therapeutic agent in treating AD.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387195","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 and antifungal activities of small molecule arylthiazolamine derivatives. 小分子芳基噻唑胺衍生物的合成和抗真菌活性。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-08 DOI: 10.1007/s11030-024-11002-8

Xu Zhong, Jian He, Taigui Ma, Guobin Chen, Yong Zhang, Min Zhang, Lei Tang, Yong Li, Lingling Fan

{"title":"Synthesis and antifungal activities of small molecule arylthiazolamine derivatives.","authors":"Xu Zhong, Jian He, Taigui Ma, Guobin Chen, Yong Zhang, Min Zhang, Lei Tang, Yong Li, Lingling Fan","doi":"10.1007/s11030-024-11002-8","DOIUrl":"https://doi.org/10.1007/s11030-024-11002-8","url":null,"abstract":"Developing new fungicides to compensate for the deficiencies of existing fungicides resistance in phytopathogenic fungi is a research hotspot in the field of pesticides. Aiming to discover novel template small molecules with excellent antifungal activity, thirty-eight arylthiazolamine derivatives were synthesized through bromination, cyclization, halogenation, and acylation reactions. The synthesized compounds were screened for antifungal activity against ten typical fungal pathogens, and some halogenated arylthiazolamines and amides exhibited excellent broad-spectrum antifungal activity, especially compounds 4m (3.96-47.76 μg/mL), 5k (0.10-7.70 μg/mL) and 5n (2.08-11.21 μg/mL). Among them, compound 5k provided comparable protection and curative effects to chloroticonil and boscalid against B. dothidea and V. mali infection in apple and apple tree branches, respectively, and it could exert antifungal effects by inhibiting the differentiation of mycelium spores, spore germination, and bud tube growth. This study provides high-efficiency and inexpensive candidate compounds for managing of diseases caused by plant pathogenic fungi.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387197","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

Design, synthesis, in vitro, and in silico study of benzothiazole-based compounds as a potent anti-Alzheimer agent. 苯并噻唑类化合物作为强效抗老年痴呆剂的设计、合成、体外和硅学研究。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-07 DOI: 10.1007/s11030-024-10909-6

Saquib Jalil, Ghulam Shabir, Aamer Saeed, Jamshed Iqbal

{"title":"Design, synthesis, in vitro, and in silico study of benzothiazole-based compounds as a potent anti-Alzheimer agent.","authors":"Saquib Jalil, Ghulam Shabir, Aamer Saeed, Jamshed Iqbal","doi":"10.1007/s11030-024-10909-6","DOIUrl":"https://doi.org/10.1007/s11030-024-10909-6","url":null,"abstract":"Alzheimer's disease (AD) is a multifactorial neurological disorder that involves multiple enzymes in the process of developing. Conventional monotherapies provide relief, necessitating alternative multi-targeting approaches to address AD complexity. Therefore, we synthesize N-(benzo[d]thiazol-2-yl) benzamide-based compounds and tested against monoamine oxidases (MAO-A and MAO-B). In the in vitro experimental evaluation of MAO, all the compounds displayed remarkable potency, having IC50 values in the lower micromolar range. The most potent MAO-A inhibitor was (3e) with an IC50 value of 0.92 ± 0.09 μM, whereas, (3d) was the most potent inhibitor of MAO-B with an IC50 value of 0.48 ± 0.04 μM. Moreover, Enzyme kinetics studies revealed that the potent inhibitors of MAO-A and MAO-B showed competitive mode of inhibition. Furthermore, molecular docking studies were also performed to confirm the mode of inhibition and obtain an intuitive picture of potent inhibitors. It also revealed several important interactions, particularly hydrogen bonding interaction. All the newly synthesized compounds showed good ADME pharmacokinetic profile and followed Lipinski rule; these compounds represent promising hits for the development of promising lead compounds for AD treatment.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379840","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

Modulating JAK2/STAT3 signaling by quercetin in Qiling Baitouweng Tang: a potential therapeutic approach for diffuse large B-cell lymphoma. 祁苓白头翁汤中的槲皮素可调节 JAK2/STAT3 信号：弥漫大 B 细胞淋巴瘤的潜在治疗方法。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-05 DOI: 10.1007/s11030-024-10999-2

Xin-Zhuo Zhan, Tian-Hua Wei, Chen Huang, Hui Yu, Xiao-Li Chen, Xiang-Tu Kong, Zhi-Hao Shang, Shan-Liang Sun, Meng-Yi Lu, Hai-Wen Ni

{"title":"Modulating JAK2/STAT3 signaling by quercetin in Qiling Baitouweng Tang: a potential therapeutic approach for diffuse large B-cell lymphoma.","authors":"Xin-Zhuo Zhan, Tian-Hua Wei, Chen Huang, Hui Yu, Xiao-Li Chen, Xiang-Tu Kong, Zhi-Hao Shang, Shan-Liang Sun, Meng-Yi Lu, Hai-Wen Ni","doi":"10.1007/s11030-024-10999-2","DOIUrl":"https://doi.org/10.1007/s11030-024-10999-2","url":null,"abstract":"Qiling Baitouweng Tang (QLBTWT) is a traditional clinical formula for treating diffuse large B-cell lymphoma (DLBCL), but its molecular action is not fully understood. This research is utilized in silico analysis and liquid chromatography tandem mass spectrometry (LC‒MS/MS) to identify the active constituents of QLBTWT with anti-DLBCL properties and their targets. The study identified 14 compounds, including quercetin, naringenin, and astilbin, as potentially effective against DLBCL. Molecular modeling highlighted the favorable interaction of quercetin with the JAK2 protein. In vitro studies confirmed the ability of quercetin to inhibit DLBCL cell growth and migration while inducing apoptosis and causing G2/M phase cell cycle arrest. Molecular dynamics simulations revealed that quercetin binds to JAK2 as a type II inhibitor. In vivo studies in U2932 xenograft models demonstrated that QLBTWT inhibited tumor growth in a dose-dependent manner, which was associated with the JAK2/STAT3 signaling pathway. Overall, this study elucidates the therapeutic effect of QLBTWT on DLBCL through quercetin-mediated suppression of the JAK2/STAT3 pathway, offering novel therapeutic insights for DLBCL.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378961","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

Design, synthesis, and computational analysis (molecular docking, DFT, MEP, RDG, ELF) of diazepine and oxazepine sulfonamides: biological evaluation for in vitro and in vivo anti-inflammatory, antimicrobial, and cytotoxicity predictions. 二氮杂卓和氧氮杂卓磺胺类药物的设计、合成和计算分析（分子对接、DFT、MEP、RDG、ELF）：体外和体内抗炎、抗菌和细胞毒性预测的生物学评估。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-02 DOI: 10.1007/s11030-024-10996-5

Sangar Ali Hassan, Dara Muhammed Aziz, Dana Ali Kader, Shwana Muhamad Rasul, Meer Ali Muhamad, Alla Ahmad Muhammedamin

引用次数: 0

Design, synthesis and biological evaluation of thienopyridine derivatives as c-Met kinase inhibitors. 作为 c-Met 激酶抑制剂的噻吩吡啶衍生物的设计、合成和生物学评价。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-02 DOI: 10.1007/s11030-024-10998-3

Tianyu Xie, Wenbo Hu, Lin You, Xin Wang

{"title":"Design, synthesis and biological evaluation of thienopyridine derivatives as c-Met kinase inhibitors.","authors":"Tianyu Xie, Wenbo Hu, Lin You, Xin Wang","doi":"10.1007/s11030-024-10998-3","DOIUrl":"https://doi.org/10.1007/s11030-024-10998-3","url":null,"abstract":"With cabozantinib as the precursor, a novel small molecule inhibitors of c-Met kinase with thieno [2,3-b] pyridine as the scaffold were designed, synthesized and evaluated for their biological activity against A549, Hela and MCF-7 cell lines. The in vitro activities of 16 compounds were tested by MTT method with cabozantinib as control drug. Most compounds had moderate to strong inhibitory activities on cells. Among them, compound 10 had the strongest inhibitory activity, which was superior to the lead compound cabozantinib. Its IC50 values for A549, Hela and MCF-7 cells were 0.005, 2.833 and 13.581 μM, respectively. The colony formation assay demonstrated that compound 10 significantly inhibited the colony formation of A549 cells and suppressed their growth in a concentration-dependent manner. The wound healing assay showed that compound 10 could effectively inhibit the migration of cancer cells compared to a blank control group. The AO/EB assay demonstrated that compound 10 possesses the capability to effectively trigger apoptosis in a concentration-dependent manner. The elementary structure-activity relationship, molecular docking and pharmacokinetics studies revealed the significance of thieno [2,3-b] pyridine derivatives in anti-tumor activity.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360910","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

An insight on medicinal attributes of 1,2,3- and 1,2,4-triazole derivatives as alpha-amylase and alpha-glucosidase inhibitors. 对1,2,3-和1,2,4-三唑衍生物作为α-淀粉酶和α-葡萄糖苷酶抑制剂的药用特性的深入了解。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-01 Epub Date: 2023-09-21 DOI: 10.1007/s11030-023-10728-1

Anushka Sharma, Rahul Dubey, Ritu Bhupal, Preeti Patel, Sant Kumar Verma, Savas Kaya, Vivek Asati

{"title":"An insight on medicinal attributes of 1,2,3- and 1,2,4-triazole derivatives as alpha-amylase and alpha-glucosidase inhibitors.","authors":"Anushka Sharma, Rahul Dubey, Ritu Bhupal, Preeti Patel, Sant Kumar Verma, Savas Kaya, Vivek Asati","doi":"10.1007/s11030-023-10728-1","DOIUrl":"10.1007/s11030-023-10728-1","url":null,"abstract":"Diabetes Mellitus (DM) is the globe's common leading disease which is caused by high consumption of glucose. DM compiles groups of metabolic disorders which are characterized by inadequate secretion of insulin from pancreas, resulting in hyperglycemia condition. Many enzymes play a vital role in the metabolism of carbohydrate known as α-amylase and α-glucosidase which is calcium metalloenzyme that leads to breakdown of complex polysaccharides into glucose. To tackle this problem, search for newer antidiabetic drugs is the utmost need for the treatment and/or management of increasing diabetic burden. The inhibition of α-amylase and α-glucosidase is one of the effective therapeutic approaches for the development of antidiabetic therapeutics. The exhaustive literature survey has shown the importance of medicinally privileged triazole specifically 1,2,3-triazol and 1,2,4-triazoles scaffold tethered, fused and/or clubbed with other heterocyclic rings structures as promising agents for designing and development of novel antidiabetic therapeutics. Molecular hybrids namely pyridazine-triazole, pyrazoline-triazole, benzothiazole-triazole, benzimidazole-triazole, curcumin-triazole, (bis)coumarin-triazole, acridine-9-carboxamide linked triazole, quinazolinone-triazole, xanthone-triazole, thiazolo-triazole, thiosemicarbazide-triazole, and indole clubbed-triazole are few examples which have shown promising antidiabetic activity by inhibiting α-amylase and/or α-glucosidase. The present review summarizes the structure-activity relationship (SAR), enzyme inhibitory activity including IC50 values, percentage inhibition, kinetic studies, molecular docking studies, and patents filed of the both scaffolds as alpha-amylase and alpha-glucosidase inhibitors, which may be used for further development of potent inhibitors against both enzymes.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":"3605-3634"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41099409","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

Review on advancements of pyranopyrazole: synthetic routes and their medicinal applications. 综述吡喃吡唑的研究进展：合成路线及其药物应用。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-01 Epub Date: 2024-01-18 DOI: 10.1007/s11030-023-10757-w

Ashok R Yadav, Ashishkumar P Katariya, Anant B Kanagare, Pramod D Jawale Patil, Chandrakant K Tagad, Satish A Dake, Pratik A Nagwade, Satish U Deshmukh

引用次数: 0

Exploring potential biomarkers and lead molecules in gastric cancer by network biology, drug repurposing and virtual screening strategies. 通过网络生物学、药物再利用和虚拟筛选策略，探索胃癌的潜在生物标志物和先导分子。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-09-30 DOI: 10.1007/s11030-024-10995-6

Sagarika Saha, Sanket Bapat, Durairaj Vijayasarathi, Renu Vyas

{"title":"Exploring potential biomarkers and lead molecules in gastric cancer by network biology, drug repurposing and virtual screening strategies.","authors":"Sagarika Saha, Sanket Bapat, Durairaj Vijayasarathi, Renu Vyas","doi":"10.1007/s11030-024-10995-6","DOIUrl":"https://doi.org/10.1007/s11030-024-10995-6","url":null,"abstract":"Gastric cancer poses a significant global health challenge, necessitating innovative approaches for biomarker discovery and therapeutic intervention. This study employs a multifaceted strategy integrating network biology, drug repurposing, and virtual screening to elucidate and expand the molecular landscape of gastric cancer. We identified and prioritized key genes implicated in gastric cancer by utilizing data from diverse databases and text-mining techniques. Network analysis underscored intricate gene interactions, emphasizing potential therapeutic targets such as CTNNB1, BCL2, TP53, etc, and highlighted ACTB among the top hub genes crucial in disease progression. Drug repurposing on 626 FDA-approved drugs for digestive system-related cancers revealed Norgestimate and Nimesulide as likely top candidates for gastric cancer, validated by molecular docking and dynamics simulations. Further, combinatorial synthesis of scaffold libraries derived from known chemotypes generated 56,160 virtual compounds, of which 76 new compounds were prioritized based on promising binding affinities and interactions at critical residues. Hotspot residue analysis identified GLU 214 and others as essential for ligand binding stability, enhancing compound efficacy and specificity. These findings support the therapeutic potential of targeting beta-actin protein in gastric cancer treatment, suggesting a future for further experimental validation and clinical translation. In conclusion, this study highlights the potential of repurposable drugs and virtual screening which can be used in combination with existing anti-gastric cancer drugs for gastric cancer therapy, emphasizing the role of computational methodologies in drug discovery.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338890","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

Comprehensive investigation of network pharmacology, computational modeling, and pharmacokinetic assessment to evaluate the efficacy of flavonoids in rheumatoid arthritis. 综合研究网络药理学、计算模型和药代动力学评估，评估类黄酮对类风湿性关节炎的疗效。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-09-30 DOI: 10.1007/s11030-024-10989-4

Sukanya Vijayan, Thirumal Margesan

{"title":"Comprehensive investigation of network pharmacology, computational modeling, and pharmacokinetic assessment to evaluate the efficacy of flavonoids in rheumatoid arthritis.","authors":"Sukanya Vijayan, Thirumal Margesan","doi":"10.1007/s11030-024-10989-4","DOIUrl":"https://doi.org/10.1007/s11030-024-10989-4","url":null,"abstract":"Rheumatoid arthritis is a chronic autoimmune disease characterized by inflammation and joint damage, imposing a significant burden on affected individuals worldwide. Flavonoids, a class of natural compounds abundant in various plant-based foods, have shown promising anti-inflammatory and immunomodulatory effects, suggesting their potential as therapeutic agents for RA. In this study, we conducted a comprehensive investigation of identified LCMS compounds utilizing network pharmacology, computational modeling, in silico approaches, and pharmacokinetic assessment to evaluate the efficacy of flavonoids in RA treatment. The study identified 5 flavonoid structures with common targets via LCMS and Integration of network pharmacology approaches enabled a comprehensive evaluation of the pharmacological profile of flavonoids in the context of RA treatment, guiding the selection of promising candidates for further experimental validation and clinical development. The top 10 targets were AKT1, PI3KR1, CDK2, EGFR, CDK6, NOS2, FLT3, ALOX5, CCNB1, and PTPRS via PPI network. The investigation emphasized several pathways, including the AGE-RAGE signaling pathway, resistance to EGFR tyrosine kinase inhibitors, the PI3K-AKT signaling network, and the Rap 1 signaling pathway. In silico studies estimated binding affinities that ranged from - 7.0 to - 10.0 kcal/mol. Schaftoside and Vitexin showed no toxicity in computational approach and found suitable for further investigations. Overall, our study underscores the potential of flavonoids as therapeutic agents for RA and highlights the utility of integrative approaches combining network pharmacology, computational modeling, in silico methods, and pharmacokinetic assessment in drug discovery and development processes.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338888","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