{"title":"量身定制的吡唑-苯并噻唑混合物的合成、抗癌评估、硅内 ADMET 和分子对接研究","authors":"Omkar Bains, Ashish Kumar, Raj Kamal, Rasdeep Kour, Simrandeep Kaur, Satwinderjeet Kaur, Raman Jangra, Purshotam Sharma, Ravinder Kumar","doi":"10.1002/ajoc.202400187","DOIUrl":null,"url":null,"abstract":"The present article demonstrates the regioselective synthesis, characterization, and biological evaluation of eighteen novel pyrazolo‐benzothiazole hybrid molecules 5a‐5r. We have utilized β,β‐ditosyloxy ketones protocol to synthesize these hybrid molecules. The synthesized compounds were tested for their in‐vitro antiproliferative activities using MTT assay against breast cancer (MCF‐7), cervical cancer (HeLa), and Lung cancer (A549) cell lines. Hybrid molecules 5a, 5m, 5n, and 5o with IC50 values of 0.359 mM, 0.051 mM, 0.079 mM, and 0.259 mM respectively exhibited admirable growth inhibitory activities against MCF‐7 cancer cells even better than reference carboplatin drug having IC50 (0.439 mM). Compound 5k with IC50 value of 0.765 mM was found to be the most potent antiproliferative agent for the HeLa cancer cells. Moreover, hybrid molecule 5f with IC50 value of 0.706 mM exhibited better inhibitory activity against A549 cancer cells in comparison to the reference carboplatin drug having IC50 (0.805 mM). The mechanism of cellular toxicity was studied using Annexin V‐FITC/PI double staining method and cell cycle assay. Molecular docking studies for all the synthesized compounds have been performed in the binding pocket of VEGFR‐2 sites (PBD code: 4ASD). Finally, the ADMET profile of the potent molecules was also investigated to predict their drug‐likeness behaviour.","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis, anticancer evaluation, in‐silico ADMET and molecular docking studies for tailored pyrazolo‐benzothiazole hybrids\",\"authors\":\"Omkar Bains, Ashish Kumar, Raj Kamal, Rasdeep Kour, Simrandeep Kaur, Satwinderjeet Kaur, Raman Jangra, Purshotam Sharma, Ravinder Kumar\",\"doi\":\"10.1002/ajoc.202400187\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The present article demonstrates the regioselective synthesis, characterization, and biological evaluation of eighteen novel pyrazolo‐benzothiazole hybrid molecules 5a‐5r. We have utilized β,β‐ditosyloxy ketones protocol to synthesize these hybrid molecules. The synthesized compounds were tested for their in‐vitro antiproliferative activities using MTT assay against breast cancer (MCF‐7), cervical cancer (HeLa), and Lung cancer (A549) cell lines. Hybrid molecules 5a, 5m, 5n, and 5o with IC50 values of 0.359 mM, 0.051 mM, 0.079 mM, and 0.259 mM respectively exhibited admirable growth inhibitory activities against MCF‐7 cancer cells even better than reference carboplatin drug having IC50 (0.439 mM). Compound 5k with IC50 value of 0.765 mM was found to be the most potent antiproliferative agent for the HeLa cancer cells. Moreover, hybrid molecule 5f with IC50 value of 0.706 mM exhibited better inhibitory activity against A549 cancer cells in comparison to the reference carboplatin drug having IC50 (0.805 mM). The mechanism of cellular toxicity was studied using Annexin V‐FITC/PI double staining method and cell cycle assay. Molecular docking studies for all the synthesized compounds have been performed in the binding pocket of VEGFR‐2 sites (PBD code: 4ASD). Finally, the ADMET profile of the potent molecules was also investigated to predict their drug‐likeness behaviour.\",\"PeriodicalId\":130,\"journal\":{\"name\":\"Asian Journal of Organic Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Asian Journal of Organic Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1002/ajoc.202400187\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asian Journal of Organic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1002/ajoc.202400187","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
Synthesis, anticancer evaluation, in‐silico ADMET and molecular docking studies for tailored pyrazolo‐benzothiazole hybrids
The present article demonstrates the regioselective synthesis, characterization, and biological evaluation of eighteen novel pyrazolo‐benzothiazole hybrid molecules 5a‐5r. We have utilized β,β‐ditosyloxy ketones protocol to synthesize these hybrid molecules. The synthesized compounds were tested for their in‐vitro antiproliferative activities using MTT assay against breast cancer (MCF‐7), cervical cancer (HeLa), and Lung cancer (A549) cell lines. Hybrid molecules 5a, 5m, 5n, and 5o with IC50 values of 0.359 mM, 0.051 mM, 0.079 mM, and 0.259 mM respectively exhibited admirable growth inhibitory activities against MCF‐7 cancer cells even better than reference carboplatin drug having IC50 (0.439 mM). Compound 5k with IC50 value of 0.765 mM was found to be the most potent antiproliferative agent for the HeLa cancer cells. Moreover, hybrid molecule 5f with IC50 value of 0.706 mM exhibited better inhibitory activity against A549 cancer cells in comparison to the reference carboplatin drug having IC50 (0.805 mM). The mechanism of cellular toxicity was studied using Annexin V‐FITC/PI double staining method and cell cycle assay. Molecular docking studies for all the synthesized compounds have been performed in the binding pocket of VEGFR‐2 sites (PBD code: 4ASD). Finally, the ADMET profile of the potent molecules was also investigated to predict their drug‐likeness behaviour.
期刊介绍:
Organic chemistry is the fundamental science that stands at the heart of chemistry, biology, and materials science. Research in these areas is vigorous and truly international, with three major regions making almost equal contributions: America, Europe and Asia. Asia now has its own top international organic chemistry journal—the Asian Journal of Organic Chemistry (AsianJOC)
The AsianJOC is designed to be a top-ranked international research journal and publishes primary research as well as critical secondary information from authors across the world. The journal covers organic chemistry in its entirety. Authors and readers come from academia, the chemical industry, and government laboratories.