Molecular Diversity最新文献

Based on magnetically recoverable catalysts: a green strategy to sulfonamides. 基于磁性可回收催化剂：磺胺类药物的绿色战略。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-11-04 DOI: 10.1007/s11030-024-11030-4

Chuang Song, Mosstafa Kazemi

引用次数: 0

Screening for antimicrobial and antioxidant activities of quinazolinone based isoxazole and isoxazoline derivatives, synthesis and In silico studies. 基于喹唑啉酮的异噁唑和异噁唑啉衍生物的抗菌和抗氧化活性筛选、合成和硅学研究。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-11-02 DOI: 10.1007/s11030-024-11032-2

Nagaraju Myakala, Vishnu Thumma, Kotaiah Kandula, Nagamani Rayala, Lakshmi Satya Boddu, Kanaka Durga Bhavani Anagani

{"title":"Screening for antimicrobial and antioxidant activities of quinazolinone based isoxazole and isoxazoline derivatives, synthesis and In silico studies.","authors":"Nagaraju Myakala, Vishnu Thumma, Kotaiah Kandula, Nagamani Rayala, Lakshmi Satya Boddu, Kanaka Durga Bhavani Anagani","doi":"10.1007/s11030-024-11032-2","DOIUrl":"https://doi.org/10.1007/s11030-024-11032-2","url":null,"abstract":"Two novel series of quinazolinone based isoxazole and isoxazoline hybrid compounds were synthesized from 6-aminoquinazolinone as a key precursor. The title compounds were achieved in synthetic routes via propargylation and allylation reactions of the precursor followed by cyclization with various chloroximes. The new compounds 4a-g and 6a-g were screened for their antimicrobial activity against two Gram-positive bacteria, two Gram-negative bacteria and two fungi by employing Ampicillin and Itraconazole as standard reference. Among all, the 4-bromosubstituted analogues in isoxazole series 4d and in isoxazoline series 6d demonstrated potent activity against all bacterial and fungal strains compared to Ampicillin as well as Itraconazole. The MIC of these compounds were determined as 0.012 μM. The antioxidant investigation revealed that compounds 4f and 6f with dimethyl substitution, exhibited significant activity. Their respective IC50 values were 1.28 ± 0.33, 1.39 ± 0.38 µM and 1.07 ± 0.24, 1.10 ± 0.26 µM, when compared to Ascorbic acid. The compounds 4 g and 6 g with dichloro substitution, exhibited promising results with IC50 values were 2.72 ± 0.34 µM and 2.78 ± 0.41 µM for 4 g, and 2.24 ± 0.93 µM and 2.45 ± 0.53 µM for 6 g, respectively. Their antimicrobial and antioxidant activities were authenticated by the molecular docking study against crystal structure of DNA gyrase and NADPH oxidase. The predicted ADME properties of these molecules progressed favourable drug-likeness properties.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563626","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

A potent dual inhibitor targeting COX-2 and HDAC of acute myeloid leukemia cells. 一种针对急性髓性白血病细胞 COX-2 和 HDAC 的强效双重抑制剂。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-31 DOI: 10.1007/s11030-024-11000-w

Xiang Qin, Xueting Wang, Chunmei Yang, Fan Wang, Tingting Fang, Didi Gu, Qulian Guo, Qiuyu Meng, Wenjun Liu, Lu Yang

{"title":"A potent dual inhibitor targeting COX-2 and HDAC of acute myeloid leukemia cells.","authors":"Xiang Qin, Xueting Wang, Chunmei Yang, Fan Wang, Tingting Fang, Didi Gu, Qulian Guo, Qiuyu Meng, Wenjun Liu, Lu Yang","doi":"10.1007/s11030-024-11000-w","DOIUrl":"10.1007/s11030-024-11000-w","url":null,"abstract":"Acute myeloid leukemia (AML) is an aggressive cancer with complex issues of drug resistance and a poor prognosis; thus, effective therapeutics is urgently needed for AML. In this study, we designed and synthesized dual cyclooxygenase-2 (COX-2) and histone deacetylase (HDAC) inhibitors, IMC-HA and IMC-OPD, and applied them for the treatment of AML. IMC-HA comprised a COX-2 inhibitor skeleton of indomethacin (IMC) and an HDAC inhibitor moiety of the hydroxamic group and was found to exhibit potent antiproliferative activity against AML cells (THP-1 and U937) and low cytotoxicity toward normal cells. Molecular docking simulations suggested that IMC-HA had a high binding affinity for HDAC and COX-2, with binding energies of -6.8 and -9.0 kcal/mol, respectively. Mechanistic studies revealed that IMC-HA induced apoptosis and G0/G1 phase arrest in AML cells, which were characterized by alterations in the expression of apoptotic and cell cycle-related proteins. Further study demonstrated that IMC-HA also inhibited the MEK/ERK signaling pathway in AML cells. Overall, we believe that IMC-HA could serve as a potent COX-2/HDAC dual inhibitor and improve the treatment of AML.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556865","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 advances in microbially derived chlorinated antiparasitic compounds. 微生物衍生氯化抗寄生虫化合物的最新进展。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-30 DOI: 10.1007/s11030-024-11018-0

Samriti Saklani, Shruti Chaudhari, Gayatri Shukla, Harishankar Gound, Dewashish Awasarmol, Ravindra Taware

{"title":"Recent advances in microbially derived chlorinated antiparasitic compounds.","authors":"Samriti Saklani, Shruti Chaudhari, Gayatri Shukla, Harishankar Gound, Dewashish Awasarmol, Ravindra Taware","doi":"10.1007/s11030-024-11018-0","DOIUrl":"https://doi.org/10.1007/s11030-024-11018-0","url":null,"abstract":"Parasitic diseases remain a significant global health challenge, especially in developing countries, contributing to approximately one million deaths annually. Notably, among the 143 FDA-approved antiparasitic drugs, thirty-four possess chlorine in their chemical structure, highlighting the importance of chlorine substitution. This underscores the significance of chlorine atoms in elucidating structure-activity relationships crucial for drug discovery, aiming to develop safer, more selective, and environmentally friendly molecules with enhanced efficacy. Of particular interest some are naturally occurring chlorinated metabolites derived from PKS, NRPS, and PKS-NRPS biosynthetic pathways, which offer the potential for further manipulation. However, there is limited literature on antiparasitic chlorinated compounds from microbial sources. To address this, we conducted a comprehensive literature survey from 1963 to the present, identifying 28 chlorinated compounds with confirmed antiparasitic properties. This review underscores the potential of enzymatic machinery for selective chlorine substitution, offering insights for biochemists and synthetic chemists to develop versatile chlorinated compounds through synthetic biology, combinatorial chemistry, and organic synthesis.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542813","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

Repurposed pharmacotherapy: targeting cathepsin L with repurposed drugs in virtual screening. 重塑药物疗法：在虚拟筛选中使用重塑药物靶向 cathepsin L。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-29 DOI: 10.1007/s11030-024-11022-4

Mohammad Khalid, Mohammed H Alqarni, Ahmed I Foudah

{"title":"Repurposed pharmacotherapy: targeting cathepsin L with repurposed drugs in virtual screening.","authors":"Mohammad Khalid, Mohammed H Alqarni, Ahmed I Foudah","doi":"10.1007/s11030-024-11022-4","DOIUrl":"https://doi.org/10.1007/s11030-024-11022-4","url":null,"abstract":"Proteolytic enzymes are closely associated with cancer and are important in different phases, including tumor growth, angiogenesis, and metastasis. Despite efforts to target matrix metalloproteases (MMPs), clinical trials have often resulted in various side effects such as musculoskeletal pain, joint stiffness, and tendinitis, making them less optimal for chronic cancer treatment. Thus, there is a need for the identification of other protease targets that would provide different approaches towards the management of cancer. Of these targets, Cathepsin L (CatL) is a lysosomal cysteine protease that has been identified as a therapeutic target that is implicated in cancer development and metastasis. In this study, we performed an integrated approach of virtual screening and molecular dynamics (MD) simulations to identify the potential inhibitors of CatL from a library of drugs that have been used for different treatments. Towards this goal, we performed virtual screening of the DrugBank database and found two repurposed drugs, Irinotecan and Nilotinib, against CatL based on their docking profiles, favorable docking scores, and specific interaction with the CatL binding pocket. MD simulations of the Irinotecan and Nilotinib bound structures with CatL were carried out, and the analysis showed that both these compounds could function as CatL inhibitors as the protein-ligand interactions were stable for 300 ns. This study highlights the robustness of these drugs bound to CatL and indicates that they could be repurposed for the treatment of cancer. These findings endorse the use of computer-based approaches for the identification of new inhibitors, and the present study will be a useful resource for future experimental research towards the targeting of CatL in cancer therapeutics.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542814","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

Cobalt-catalyzed reductive cross-coupling: a review. 钴催化的还原交叉偶联：综述。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-28 DOI: 10.1007/s11030-024-11017-1

Shamoon Hassan, Muhammad Bilal, Shehla Khalid, Nasir Rasool, Muhammad Imran, Adnan Ali Shah

引用次数: 0

Exploration of anti-atherosclerotic activity of 1,8-cineole through network pharmacology, molecular docking, and in vivo efficacy studies in high-fat-diet-induced atherosclerosis in hamsters. 通过网络药理学、分子对接和高脂饮食诱导仓鼠动脉粥样硬化的体内药效研究，探索 1,8-ineole 的抗动脉粥样硬化活性。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-27 DOI: 10.1007/s11030-024-11015-3

Shreya R Savla, Lokesh Kumar Bhatt

{"title":"Exploration of anti-atherosclerotic activity of 1,8-cineole through network pharmacology, molecular docking, and in vivo efficacy studies in high-fat-diet-induced atherosclerosis in hamsters.","authors":"Shreya R Savla, Lokesh Kumar Bhatt","doi":"10.1007/s11030-024-11015-3","DOIUrl":"https://doi.org/10.1007/s11030-024-11015-3","url":null,"abstract":"The anti-atherogenic potential of liver X receptors (LXRs) has been attributed to their inhibitory role in macrophage-mediated inflammation and promotion of reverse cholesterol transport. This study aimed to evaluate the efficacy of an LXR agonist, 1,8-cineole (Eucalyptol), in atherosclerosis through network pharmacology, molecular docking, and in vivo efficacy studies in high-fat-diet-induced atherosclerosis in hamsters. Network pharmacology analysis was performed by identifying potential targets of 1,8-Cineole and atherosclerosis, followed by the construction of component-target-disease and protein-protein interaction networks. Gene Ontology and KEGG pathway enrichment analysis of targets were performed. The top 5 targets were selected for molecular docking studies. Atherosclerosis was induced in male Golden Syrian hamsters, and the results of network pharmacology were verified. Fifty-one overlapped targets were identified for 1,8-cineole and atherosclerosis. In the protein-protein interaction studies, the top 5 ranked proteins were PPARG, FXR, ABCA-1, ABCG1, and LXRΑ. KEGG pathway analysis and molecular docking showed that ABCA-1 and LXRΑ were correlated in atherosclerosis. Animal studies showed amelioration of atherosclerotic lesions in the aorta of animals treated with 1,8-cineole compared to disease control aortas. A dose-dependent attenuation in ABCA-1 levels and inflammatory markers was observed in animals treated with 1,8-cineole, comparable to its levels in normal animals. In conclusion, 1,8-cineole showed anti-atherosclerotic effects in Golden Syrian hamsters via LXRΑ-induced ABCA-1 overexpression.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492635","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 derivatives of capsaicin as a potent hypolipidemic and anti-obesity agent. 辣椒素的新型衍生物是一种有效的降血脂和抗肥胖剂。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-24 DOI: 10.1007/s11030-024-10971-0

Feng Li, Yingwei Hou, Haipeng Pang, Xiaofeng Song, Wenbao Li

引用次数: 0

Advancements of anticancer agents by targeting the Hippo signalling pathway: biological activity, selectivity, docking analysis, and structure-activity relationship. 针对 Hippo 信号通路的抗癌药物研究进展：生物活性、选择性、对接分析和结构-活性关系。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-22 DOI: 10.1007/s11030-024-11009-1

E Haripriya, K Hemalatha, Gurubasavaraja Swamy Purawarga Matada, Rohit Pal, Pronoy Kanti Das, M D Ashadul Sk, S Mounika, M P Viji, I Aayishamma, K R Jayashree

{"title":"Advancements of anticancer agents by targeting the Hippo signalling pathway: biological activity, selectivity, docking analysis, and structure-activity relationship.","authors":"E Haripriya, K Hemalatha, Gurubasavaraja Swamy Purawarga Matada, Rohit Pal, Pronoy Kanti Das, M D Ashadul Sk, S Mounika, M P Viji, I Aayishamma, K R Jayashree","doi":"10.1007/s11030-024-11009-1","DOIUrl":"https://doi.org/10.1007/s11030-024-11009-1","url":null,"abstract":"The Hippo signalling pathway is prominent and governs cell proliferation and stem cell activity, acting as a growth regulator and tumour suppressor. Defects in Hippo signalling and hyperactivation of its downstream effector's Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) play roles in cancer development, implying that pharmacological inhibition of YAP and TAZ activity could be an effective cancer treatment strategy. Conversely, YAP and TAZ can also have beneficial effects in promoting tissue repair and regeneration following damage, therefore their activation may be therapeutically effective in certain instances. Recently, a complex network of intracellular and extracellular signalling mechanisms that affect YAP and TAZ activity has been uncovered. The YAP/TAZ-TEAD interaction leads to tumour development and the protein structure of YAP/TAZ-TEAD includes three interfaces and one hydrophobic pocket. There are clinical and preclinical trial drugs available to inhibit the hippo signalling pathway, but these drugs have moderate to severe side effects, so researchers are in search of novel, potent, and selective hippo signalling pathway inhibitors. In this review, we have discussed the hippo pathway in detail, including its structure, activation, and role in cancer. We have also provided the various inhibitors under clinical and preclinical trials, and advancement of small molecules their detailed docking analysis, structure-activity relationship, and biological activity. We anticipate that the current study will be a helpful resource for researchers.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455374","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

AI-DPAPT: a machine learning framework for predicting PROTAC activity. AI-DPAPT：预测 PROTAC 活动的机器学习框架。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-10-19 DOI: 10.1007/s11030-024-11011-7

Amr S Abouzied, Bahaa Alshammari, Hayam Kari, Bader Huwaimel, Saad Alqarni, Shaymaa E Kassab

{"title":"AI-DPAPT: a machine learning framework for predicting PROTAC activity.","authors":"Amr S Abouzied, Bahaa Alshammari, Hayam Kari, Bader Huwaimel, Saad Alqarni, Shaymaa E Kassab","doi":"10.1007/s11030-024-11011-7","DOIUrl":"https://doi.org/10.1007/s11030-024-11011-7","url":null,"abstract":"Proteolysis Targeting Chimeras are part of targeted protein degradation (TPD) techniques, which are significant for pharmacological and therapy development. Small-molecule interaction with the targeted protein is a complicated endeavor and a challenge to predict the proteins accurately. This study used machine learning algorithms and molecular fingerprinting techniques to build an AI-powered PROTAC Activity Prediction Tool that could predict PROTAC activity by examining chemical structures. The chemical structures of a diverse set of PROTAC drugs and their corresponding activities are selected as a dataset for training the tool. The processes used in this study included data preparation, feature extraction, and model training. Further, evaluation was done for the performance of the various classifiers, such as AdaBoost, Support Vector Machine, Random Forest, Gradient Boosting, and Multi-Layer Perceptron. The findings show that the methods selected here depict accurate PROTAC activities. All the models in this study showed an ROC curve better than 0.9, while the random forest on the test set of the AI-DPAPT had an area under the curve score of 0.97, thus showing accurate results. Furthermore, the study revealed significant insights into the molecular features that can influence the functions of the PROTAC. These findings can potentially increase the understanding of the structure-activity correlations involved in the TPD. Overall, the investigation contributes to computational drug development by introducing this platform powered by artificial intelligence that predicts the function of PROTAC. In addition, it sped up the processes of identifying and improving previously unknown medications. The AI-DPAPT platform can be accessed online using a web server at https://ai-protac.streamlit.app/ .","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455375","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