{"title":"新型磺胺甲噁唑和 1-(2-氟苯基)哌嗪衍生物通过抑制 BCL2 而成为潜在的凋亡和抗增生药物;设计、合成、生物学评价和对接研究。","authors":"Nagalakshmamma Vadabingi, Venkataswamy Mallepogu, Rani E Mallapu, Chiranjeevi Pasala, Sumithra Poreddy, Poojitha Bellala, Umamaheswari Amineni, Suresh Reddy Cirandur, Balaji Meriga","doi":"10.1007/s13205-024-04111-6","DOIUrl":null,"url":null,"abstract":"<p><p>In the present study, a novel series of sulfamethoxazole and 1-(2-fluorophenyl) piperazine derivatives were designed, synthesized and characterized by FTIR, <sup>I</sup>H NMR,<sup>13</sup>C NMR, Mass spectrometry, CHN data, and evaluated for their efficiency as BCL2 inhibitors that could lead to potential antiproliferative activity. The ten newly synthesized compounds were screened for their therapeutic activity using MDA-MB-231 breast cancer cell lines. All the test compounds exhibited moderate to high cytotoxic activity in MTT assay. Among them, compounds <b>3e</b> and <b>6b</b> exhibited promising antitumor activity, as evidenced by their IC<sub>50</sub> values of 16.98 and 17.33 μM respectively. In addition, both compounds <b>3e</b> and <b>6b</b> displayed potential antioxidant and apoptosis induction properties. The qRT-PCR analysis showed down regulation of BCL2 expression and up regulation of Casp3 expression in <b>3e</b> and <b>6b</b> treated MDA-MB-231 cells. Further, the interaction between critical amino acids of the active domains of BCL2 and <b>3e</b> and <b>6b</b> was evaluated by MD simulation, and the results reflected the potent inhibitory activities of <b>3e</b> and <b>6b</b>. In summary, the novel compounds <b>3e</b> and <b>6b</b> demonstrate their potent anti-cancer properties by inducing apoptosis and selectively targeting BCL2 and caspases-3.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13205-024-04111-6.</p>","PeriodicalId":7067,"journal":{"name":"3 Biotech","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480306/pdf/","citationCount":"0","resultStr":"{\"title\":\"Novel sulfamethoxazole and 1-(2-fluorophenyl) piperazine derivatives as potential apoptotic and antiproliferative agents by inhibition of BCL2; design, synthesis, biological evaluation, and docking studies.\",\"authors\":\"Nagalakshmamma Vadabingi, Venkataswamy Mallepogu, Rani E Mallapu, Chiranjeevi Pasala, Sumithra Poreddy, Poojitha Bellala, Umamaheswari Amineni, Suresh Reddy Cirandur, Balaji Meriga\",\"doi\":\"10.1007/s13205-024-04111-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In the present study, a novel series of sulfamethoxazole and 1-(2-fluorophenyl) piperazine derivatives were designed, synthesized and characterized by FTIR, <sup>I</sup>H NMR,<sup>13</sup>C NMR, Mass spectrometry, CHN data, and evaluated for their efficiency as BCL2 inhibitors that could lead to potential antiproliferative activity. The ten newly synthesized compounds were screened for their therapeutic activity using MDA-MB-231 breast cancer cell lines. All the test compounds exhibited moderate to high cytotoxic activity in MTT assay. Among them, compounds <b>3e</b> and <b>6b</b> exhibited promising antitumor activity, as evidenced by their IC<sub>50</sub> values of 16.98 and 17.33 μM respectively. In addition, both compounds <b>3e</b> and <b>6b</b> displayed potential antioxidant and apoptosis induction properties. The qRT-PCR analysis showed down regulation of BCL2 expression and up regulation of Casp3 expression in <b>3e</b> and <b>6b</b> treated MDA-MB-231 cells. Further, the interaction between critical amino acids of the active domains of BCL2 and <b>3e</b> and <b>6b</b> was evaluated by MD simulation, and the results reflected the potent inhibitory activities of <b>3e</b> and <b>6b</b>. 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引用次数: 0
摘要
本研究设计、合成了一系列新型磺胺甲噁唑和 1-(2-氟苯基)哌嗪衍生物,并通过傅立叶变换红外光谱(FTIR)、IH NMR、13C NMR、质谱分析和 CHN 数据对其进行了表征,评估了它们作为 BCL2 抑制剂的效率,这可能会导致潜在的抗增殖活性。利用 MDA-MB-231 乳腺癌细胞系对这十种新合成的化合物进行了治疗活性筛选。在 MTT 试验中,所有受试化合物都表现出中等到较高的细胞毒性活性。其中,化合物 3e 和 6b 的 IC50 值分别为 16.98 和 17.33 μM,显示出良好的抗肿瘤活性。此外,化合物 3e 和 6b 还具有潜在的抗氧化和诱导细胞凋亡的特性。qRT-PCR 分析表明,在 3e 和 6b 处理的 MDA-MB-231 细胞中,BCL2 表达下调,Casp3 表达上调。此外,通过 MD 模拟评估了 BCL2 活性域的关键氨基酸与 3e 和 6b 之间的相互作用,结果显示 3e 和 6b 具有很强的抑制活性。总之,新型化合物 3e 和 6b 通过诱导细胞凋亡和选择性靶向 BCL2 和 caspases-3 显示了其强大的抗癌特性:在线版本包含补充材料,可查阅 10.1007/s13205-024-04111-6。
Novel sulfamethoxazole and 1-(2-fluorophenyl) piperazine derivatives as potential apoptotic and antiproliferative agents by inhibition of BCL2; design, synthesis, biological evaluation, and docking studies.
In the present study, a novel series of sulfamethoxazole and 1-(2-fluorophenyl) piperazine derivatives were designed, synthesized and characterized by FTIR, IH NMR,13C NMR, Mass spectrometry, CHN data, and evaluated for their efficiency as BCL2 inhibitors that could lead to potential antiproliferative activity. The ten newly synthesized compounds were screened for their therapeutic activity using MDA-MB-231 breast cancer cell lines. All the test compounds exhibited moderate to high cytotoxic activity in MTT assay. Among them, compounds 3e and 6b exhibited promising antitumor activity, as evidenced by their IC50 values of 16.98 and 17.33 μM respectively. In addition, both compounds 3e and 6b displayed potential antioxidant and apoptosis induction properties. The qRT-PCR analysis showed down regulation of BCL2 expression and up regulation of Casp3 expression in 3e and 6b treated MDA-MB-231 cells. Further, the interaction between critical amino acids of the active domains of BCL2 and 3e and 6b was evaluated by MD simulation, and the results reflected the potent inhibitory activities of 3e and 6b. In summary, the novel compounds 3e and 6b demonstrate their potent anti-cancer properties by inducing apoptosis and selectively targeting BCL2 and caspases-3.
Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04111-6.
3 BiotechAgricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)
CiteScore
6.00
自引率
0.00%
发文量
314
期刊介绍:
3 Biotech publishes the results of the latest research related to the study and application of biotechnology to:
- Medicine and Biomedical Sciences
- Agriculture
- The Environment
The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.