B. Karthik, B. Ramakrishna, B. Ashok Kumar, T. Kranthi Kumar
{"title":"设计和合成一些新的苯并咪唑-1,2,3-三唑-噻唑烷-2,4-二酮共轭物作为微管蛋白聚合抑制剂","authors":"B. Karthik, B. Ramakrishna, B. Ashok Kumar, T. Kranthi Kumar","doi":"10.1134/s1068162024040307","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p><b>Objective:</b> It is worthy to note that the benzimidazole, thiazolidine-2,4-dione and 1,2,3-triazole pharmacophores have keen role in anticancer drug discovery. In order to overcome the limitations associated with reported antimitotic compounds, our group is first time combining these three pharmacophores and revealing their <i>in vitro</i> anticancer and anti-mitotic activities. <b>Methods:</b> As a part of our efforts on the development of novel anticancer agents, in this study, we concentrated on the synthesis of benzimidazole-thiazolidine-2,4-dione-1,2,3-triazoles (<b>VIIa–VIIl</b>) via piperidine catalyzed Knoevenagel condensation and Cu(I) catalyzed azide-alkyne cycloaddition reactions as key approaches. Then, <i>in vitro</i> anticancer and tubulin polymerization inhibition (<b>VIIa–VIIl</b>) were studied via IC<sub>50</sub> values. Finally, docking interactions of three potent compounds (<b>VIIg</b>), (<b>VIIh</b>), and (<b>VIIk</b>) towards α,β-tubulin were studied using AutoDock tools. <b>Results and Discussion:</b> Three compounds namely (<b>VIIg</b>), (<b>VIIh</b>), and (<b>VIIk</b>) showed better results against A549, MCF-7, and HeLa human cancer cell lines than standard drug nocodazole. In addition, compounds (<b>VIIg</b>) and (<b>VIIh</b>) have shown greater inhibitory potency with IC<sub>50</sub> values 0.62 and 0.31 μM respectively than standard Combretastatin A-4 (CA-4) against tubulin polymerization. Finally, <i>in silico</i> molecular docking studies for the compounds (<b>VIIg</b>), (<b>VIIh</b>), and (<b>VIIk</b>) with α,β-tubulin showed that they have great binding interactions with the target protein and to be specific the compound (<b>VIIh</b>) displayed highest binding energy, i.e. –9.23 kcal/mol. <b>Conclusions:</b> We propose that the remarkable <i>in vitro</i> anticancer activity of compounds (<b>VIIg</b>), (<b>VIIh</b>), and (<b>VIIk</b>), would be due to their tubulin polymerization inhibition.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design and Synthesis of Some New Benzimidazole-1,2,3-triazole-thiazolidine-2,4-dione Conjugates as Tubulin Polymerization Inhibitors\",\"authors\":\"B. Karthik, B. 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Then, <i>in vitro</i> anticancer and tubulin polymerization inhibition (<b>VIIa–VIIl</b>) were studied via IC<sub>50</sub> values. Finally, docking interactions of three potent compounds (<b>VIIg</b>), (<b>VIIh</b>), and (<b>VIIk</b>) towards α,β-tubulin were studied using AutoDock tools. <b>Results and Discussion:</b> Three compounds namely (<b>VIIg</b>), (<b>VIIh</b>), and (<b>VIIk</b>) showed better results against A549, MCF-7, and HeLa human cancer cell lines than standard drug nocodazole. In addition, compounds (<b>VIIg</b>) and (<b>VIIh</b>) have shown greater inhibitory potency with IC<sub>50</sub> values 0.62 and 0.31 μM respectively than standard Combretastatin A-4 (CA-4) against tubulin polymerization. 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Design and Synthesis of Some New Benzimidazole-1,2,3-triazole-thiazolidine-2,4-dione Conjugates as Tubulin Polymerization Inhibitors
Abstract
Objective: It is worthy to note that the benzimidazole, thiazolidine-2,4-dione and 1,2,3-triazole pharmacophores have keen role in anticancer drug discovery. In order to overcome the limitations associated with reported antimitotic compounds, our group is first time combining these three pharmacophores and revealing their in vitro anticancer and anti-mitotic activities. Methods: As a part of our efforts on the development of novel anticancer agents, in this study, we concentrated on the synthesis of benzimidazole-thiazolidine-2,4-dione-1,2,3-triazoles (VIIa–VIIl) via piperidine catalyzed Knoevenagel condensation and Cu(I) catalyzed azide-alkyne cycloaddition reactions as key approaches. Then, in vitro anticancer and tubulin polymerization inhibition (VIIa–VIIl) were studied via IC50 values. Finally, docking interactions of three potent compounds (VIIg), (VIIh), and (VIIk) towards α,β-tubulin were studied using AutoDock tools. Results and Discussion: Three compounds namely (VIIg), (VIIh), and (VIIk) showed better results against A549, MCF-7, and HeLa human cancer cell lines than standard drug nocodazole. In addition, compounds (VIIg) and (VIIh) have shown greater inhibitory potency with IC50 values 0.62 and 0.31 μM respectively than standard Combretastatin A-4 (CA-4) against tubulin polymerization. Finally, in silico molecular docking studies for the compounds (VIIg), (VIIh), and (VIIk) with α,β-tubulin showed that they have great binding interactions with the target protein and to be specific the compound (VIIh) displayed highest binding energy, i.e. –9.23 kcal/mol. Conclusions: We propose that the remarkable in vitro anticancer activity of compounds (VIIg), (VIIh), and (VIIk), would be due to their tubulin polymerization inhibition.
期刊介绍:
Russian Journal of Bioorganic Chemistry publishes reviews and original experimental and theoretical studies on the structure, function, structure–activity relationships, and synthesis of biopolymers, such as proteins, nucleic acids, polysaccharides, mixed biopolymers, and their complexes, and low-molecular-weight biologically active compounds (peptides, sugars, lipids, antibiotics, etc.). The journal also covers selected aspects of neuro- and immunochemistry, biotechnology, and ecology.