Molecular Diversity最新文献_第9页

Role of interaction mode of phenanthrene derivatives as selective PDE5 inhibitors using molecular dynamics simulations and quantum chemical calculations. 利用分子动力学模拟和量子化学计算研究菲类衍生物作为选择性 PDE5 抑制剂的相互作用模式的作用。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-07-30 DOI: 10.1007/s11030-024-10944-3

Supawadee Sainimnuan, Aunlika Chimprasit, Supa Hannongbua, Patchreenart Saparpakorn

{"title":"Role of interaction mode of phenanthrene derivatives as selective PDE5 inhibitors using molecular dynamics simulations and quantum chemical calculations.","authors":"Supawadee Sainimnuan, Aunlika Chimprasit, Supa Hannongbua, Patchreenart Saparpakorn","doi":"10.1007/s11030-024-10944-3","DOIUrl":"https://doi.org/10.1007/s11030-024-10944-3","url":null,"abstract":"<p><p>Phosphodiesterase type 5 (PDE5) inhibitors play a crucial role in blocking PDE5 to improve erectile dysfunction (ED). However, most PDE5 drugs revealed side effects including the loss of vision due to the PDE6 inhibition. Phenanthrene derivatives isolated from E. macrobulbon were previously reported as PDE5 inhibitors. Two phenanthrene derivatives (cpds 1-2) revealed better inhibition to PDE5 than PDE6 and cpd 1 is more selective to PDE5 than cpd 2. To elucidate why the phenanthrene derivatives could inhibit PDE5 and PDE6, their binding modes were investigated using molecular dynamics simulations and quantum chemical calculations, as compared to the PDE5 drugs. From the results, all four drugs and phenanthrene derivatives revealed similar π-π interactions to Phe820 in PDE5. Additional H-bond interaction to Gln817 in PDE5 resulted in better PDE5 inhibition of vardenafil and tadalafil. Moreover, cpds 1-2 were able to form the H-bond interaction with Asp764 in PDE5. In the case of the PDE6, the loss of π-π interaction to Phe776 and H-bond interaction to Gln773 indicated the important points for losing the PDE6 inhibition. In conclusion, to develop the new potent PDE5 inhibitors, not only the important interaction with PDE5 but also the interaction with PDE6 should be considered. In phenanthrene derivatives, the middle ring was significant to form π-π interactions to Phe820 in PDE5 and hydroxyl substituent was also the key part to form the H-bond interaction with Asp764 in PDE5. Principal component analysis (PCA) and free energy landscape (FEL) analysis indicated the stability of the system. The bioavailability, drug-likeness, and pharmacokinetics of phenanthrene derivatives were also predicted. These derivatives revealed good drug-likeness and GI absorption. The obtained results showed that phenanthrene derivatives could be interesting for the development of PDE5 inhibitors in the future.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854489","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

Identification of the potential Pan-CDK antagonists: tracing the path of virtual screening and inhibitory activity on lung cancer cells. 鉴定潜在的 Pan-CDK 拮抗剂：追踪虚拟筛选路径和对肺癌细胞的抑制活性。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-07-29 DOI: 10.1007/s11030-024-10939-0

Jia-Hao Tao, Ping-Lang Ruan, Jun Zhang, Yong Zhou, Cha-Xiang Guan

引用次数: 0

An updated review on 1,2,3-/1,2,4-triazoles: synthesis and diverse range of biological potential 1,2,3-/1,2,4-三唑的最新综述：合成与多种生物潜力

IF 3.8 2区化学

Molecular Diversity Pub Date : 2024-07-27 DOI: 10.1007/s11030-024-10858-0

Anirudh Pratap Singh Raman, Mohd. Aslam, Amardeep Awasthi, Anas Ansari, Pallavi Jain, Kashmiri Lal, Indra Bahadur, Prashant Singh, Kamlesh Kumari

引用次数: 0

Pyrazoline Spiro-oxindole tethered 1,2,3-triazole hybrids: Design, synthesis, antimicrobial efficacy and molecular modelling studies. 吡唑啉螺-吲哚系链 1,2,3 三唑杂化物：设计、合成、抗菌功效和分子建模研究。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-07-26 DOI: 10.1007/s11030-024-10928-3

Akanksha Bhukal, Vijay Kumar, Anirudh Pratap Singh Raman, Anil Kumar, Prashant Singh, Kashmiri Lal

{"title":"Pyrazoline Spiro-oxindole tethered 1,2,3-triazole hybrids: Design, synthesis, antimicrobial efficacy and molecular modelling studies.","authors":"Akanksha Bhukal, Vijay Kumar, Anirudh Pratap Singh Raman, Anil Kumar, Prashant Singh, Kashmiri Lal","doi":"10.1007/s11030-024-10928-3","DOIUrl":"https://doi.org/10.1007/s11030-024-10928-3","url":null,"abstract":"<p><p>Inspired from the important applications of spirocyclic compounds in medicinal chemistry, a new series of pyrazoline Spiro-oxindole tethered 1,2,3-triazole hybrids was reported via Cu(I)-catalyzed click reaction from isatin-pyrazoline linked terminal alkynes with in situ derived benzyl azides. Antimicrobial evaluation data showed that all hybrids exhibited promising efficacy towards the tested microbial strains. Antimicrobial screening as well as docking studies suggested that hybrid 6a was found to be most potent towards Aspergillus niger (MIC = 0.0122 μmol/mL) and Escherichia coli (MIC = 0.0061 μmol/mL). Molecular docking studies of 6a within the binding pockets of antibacterial and antifungal targets revealed good interactions with the binding energies of - 144.544 kcal/mol and - 154.364 kcal/mol against 1KZN (E. coli) and 3D3Z (A. niger), respectively. Further, MD simulations were performed to study the stability of the complexes formed at 300 K. Based on the RMSD trajectories, it is evident that 3D3Z-6a complex exhibits minimal deviation, whereas the 1KZN-6a complex displayed little more deviation compared to the protein but, both are in acceptable range. Moreover, 3D3Z-6a and 1KZN-6a showed maximum number of hydrogen bonds at 50 ns and 70 ns, respectively, thereby complementing the stability of these complexes.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764720","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

From antibiotic to antiviral: computational screening reveals a multi-targeting antibiotic from Streptomyces spp. against Nipah virus fusion proteins. 从抗生素到抗病毒药物：计算筛选揭示了链霉菌针对尼帕病毒融合蛋白的多靶点抗生素。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-07-26 DOI: 10.1007/s11030-024-10932-7

Nyzar Mabeth O Odchimar, Mark Andrian B Macalalad, Fredmoore L Orosco

{"title":"From antibiotic to antiviral: computational screening reveals a multi-targeting antibiotic from Streptomyces spp. against Nipah virus fusion proteins.","authors":"Nyzar Mabeth O Odchimar, Mark Andrian B Macalalad, Fredmoore L Orosco","doi":"10.1007/s11030-024-10932-7","DOIUrl":"https://doi.org/10.1007/s11030-024-10932-7","url":null,"abstract":"<p><p>Nipah Virus is a re-emerging zoonotic paramyxovirus that poses a significant threat to both swine industry and human health. The pursuit of potential antiviral agents with both preventive and therapeutic properties holds promise for targeting such viruses. To expedite this search, leveraging computational biology is essential. Streptomyces is renowned for its capacity to produce large and diverse metabolites with promising bioactivities. In the current study, we conducted a comprehensive structure-based virtual screening of 6524 Streptomyces spp. metabolites sourced from the StreptomeDB database to evaluate their potential inhibitory effects on three Nipah virus fusion (NiVF) protein conformations: NiVF pre-fusion 1-mer (NiVF-1mer), pre-fusion 3-mer (NiVF-3mer), and NiVF post-fusion (NiVF-PoF). Prior to virtual screening, the drug-likeness of Streptomyces spp. compounds was profiled using ADMET properties. From the 913 ADMET-filtered compounds, the subsequent targeted and confirmatory blind docking analysis revealed that S896 or virginiamycin M1, a known macrolide antibiotic, showed a maximum binding affinity with the NiVF proteins, suggesting a multi-targeting inhibitory property. In addition, the 200-ns molecular dynamics simulation and MM/PBSA analyses revealed stable and strong binding affinity between the NiVF-S896 complexes, indicating favorable interactions between S896 and the target proteins. These findings suggest the potential of virginiamycin M1, an antibiotic, as a promising multi-targeting antiviral drug. However, in vitro and in vivo experimental validations are necessary to assess their safety and efficacy.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764719","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 synthetic strategies for N-arylation of pyrrolidines: a potential template for biologically active molecules. 吡咯烷 N-芳基化的最新合成策略：生物活性分子的潜在模板。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-07-24 DOI: 10.1007/s11030-024-10924-7

Saeeda Mubashra, Ayesha Rafiq, Sana Aslam, Nasir Rasool, Matloob Ahmad

引用次数: 0

Functional characterization and structural prediction of hypothetical proteins in monkeypox virus and identification of potential inhibitors. 猴痘病毒假定蛋白的功能特征和结构预测以及潜在抑制剂的鉴定。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-07-24 DOI: 10.1007/s11030-024-10935-4

Reana Raen, Muhammad Muinul Islam, Redwanul Islam, Md Rabiul Islam, Tanima Jarin

{"title":"Functional characterization and structural prediction of hypothetical proteins in monkeypox virus and identification of potential inhibitors.","authors":"Reana Raen, Muhammad Muinul Islam, Redwanul Islam, Md Rabiul Islam, Tanima Jarin","doi":"10.1007/s11030-024-10935-4","DOIUrl":"https://doi.org/10.1007/s11030-024-10935-4","url":null,"abstract":"<p><p>The excessive activation of the monkeypox virus (MPXV-Congo_8-156) is linked to various skin and respiratory disorders such as rashes, fluid-filled blisters, swollen lymph nodes and encephalitis (inflammation of the brain), highlighting MPXV-Congo_8-156 as a promising target for drug intervention. Despite the effectiveness of Cidofovir, in inhibiting MPXV activity, its limited ability to penetrate the skin and its strong side effects restrict its application. To address this challenge, we screened 500 compounds capable of penetrating the skin and gastrointestinal tract to identify potent MPXV inhibitors. Various characterization schemes and structural models of MPXV-Congo_8-156 were explored with bioinformatics tools like PROTPARAM, SOPMA, SWISS-MODEL and PROCHECK. Using molecular docking in PyRx, we evaluated the binding affinities of these compounds with MPXV-Congo_8-156 and identified the top five candidates ranging from - 9.2 to - 8.8 kcal/mol. ADMET analysis indicated that all five compounds were safer alternatives, showing no AMES toxicity or carcinogenicity in toxicological assessments. Molecular dynamics (MD) simulations, conducted for 100 ns each, confirmed the docking interactions of the top five compounds alongside the control (Cidofovir), validating their potential as MPXV inhibitors. The compounds with PubChem CID numbers 4061636, 4422538, 3583576, 4856107 and 4800629 demonstrated strong support in terms of root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA) value, hydrogen bond analysis, and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analysis. Thus, our investigation identified these five compounds as promising inhibitors of MPXV, offering potential therapeutic avenues. However, further in vivo studies are necessary to validate our findings.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750814","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 antiviral activity of indole derivatives containing quinoline moiety. 含喹啉分子的吲哚衍生物的设计、合成和抗病毒活性。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-07-24 DOI: 10.1007/s11030-024-10894-w

Bangcan He, Yuzhi Hu, Yishan Qin, Yufang Zhang, Xingping Luo, Zhenchao Wang, Wei Xue

{"title":"Design, synthesis and antiviral activity of indole derivatives containing quinoline moiety.","authors":"Bangcan He, Yuzhi Hu, Yishan Qin, Yufang Zhang, Xingping Luo, Zhenchao Wang, Wei Xue","doi":"10.1007/s11030-024-10894-w","DOIUrl":"https://doi.org/10.1007/s11030-024-10894-w","url":null,"abstract":"<p><p>A series of indole derivatives containing quinoline structures were designed and synthesized. The synthesized compounds were characterized by NMR and HRMS. And W14 was performed by single crystal X-ray diffraction experiments. The antiviral activity studies showed that some of the target compounds possessed significant activity against tobacco mosaic virus (TMV). In particular, W20 had significant activity. The results of in vivo anti-TMV activity assay showed that W20 possessed the best curative and protective activities with EC<sub>50</sub> values of 84.4 and 65.7 μg/mL, which were better than ningnanmycin (NNM) 205.1 and 162.0 μg/mL, respectively. The results of Microscale thermophoresis (MST) showed that W20 had a strong binding affinity for the tobacco mosaic virus coat protein (TMV-CP) with a dissociation constant (K<sub>d</sub>) of 0.00519 μmol/L, which was superior to that of NNM (1. 65320 μmol/L). The molecular docking studies were in accordance with the experimental results. In addition, the determination of malondialdehyde (MDA) content in tobacco leaves showed that W20 improved the disease resistance of tobacco. Overall, this study shows that indole derivatives containing quinoline can be used as new antiviral agents for plant viruses for further research.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750813","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

PMTPred: machine-learning-based prediction of protein methyltransferases using the composition of k-spaced amino acid pairs PMTPred：基于机器学习的蛋白质甲基转移酶预测，使用 k 距氨基酸对的组成。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-07-21 DOI: 10.1007/s11030-024-10937-2

Arvind Kumar Yadav, Pradeep Kumar Gupta, Tiratha Raj Singh

{"title":"PMTPred: machine-learning-based prediction of protein methyltransferases using the composition of k-spaced amino acid pairs","authors":"Arvind Kumar Yadav, Pradeep Kumar Gupta, Tiratha Raj Singh","doi":"10.1007/s11030-024-10937-2","DOIUrl":"10.1007/s11030-024-10937-2","url":null,"abstract":"<div><p>Protein methyltransferases (PMTs) are a group of enzymes that help catalyze the transfer of a methyl group to its substrates. These enzymes play an important role in epigenetic regulation and can methylate various substrates with DNA, RNA, protein, and small-molecule secondary metabolites. Dysregulation of methyltransferases is implicated in various human cancers. However, in light of the well-recognized significance of PMTs, reliable and efficient identification methods are essential. In the present work, we propose a machine-learning-based method for the identification of PMTs. Various sequence-based features were calculated, and prediction models were trained using various machine-learning algorithms using a tenfold cross-validation technique. After evaluating each model on the dataset, the SVM-based CKSAAP model achieved the highest prediction accuracy with balanced sensitivity and specificity. Also, this SVM model outperformed deep-learning algorithms for the prediction of PMTs. In addition, cross-database validation was performed to ensure the robustness of the model. Feature importance was assessed using shapley additive explanations (SHAP) values, providing insights into the contributions of different features to the model’s predictions. Finally, the SVM-based CKSAAP model was implemented in a standalone tool, PMTPred, due to its consistent performance during independent testing and cross-database evaluation. We believe that PMTPred will be a useful and efficient tool for the identification of PMTs. The PMTPred is freely available for download at https://github.com/ArvindYadav7/PMTPred and http://www.bioinfoindia.org/PMTPred/home.html for research and academic use.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733162","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

Benzimidazole scaffold as a potent anticancer agent with different mechanisms of action (2016-2023). 苯并咪唑支架作为一种具有不同作用机制的强效抗癌剂（2016-2023 年）。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-07-20 DOI: 10.1007/s11030-024-10907-8

Fatma Fouad Hagar, Samar H Abbas, Eman Atef, Dalia Abdelhamid, Mohamed Abdel-Aziz

引用次数: 0