Development of Benzimidazole-Substituted Spirocyclopropyl Oxindole Derivatives as Cytotoxic Agents: Tubulin Polymerization Inhibition and Apoptosis Inducing Studies

被引:2
作者
Sakla, Akash P. [1 ]
Bazaz, Mohd Rabi [2 ]
Mahale, Ashutosh [3 ]
Sharma, Pravesh [3 ]
Valapil, Durgesh Gurukkala [1 ]
Kulkarni, Onkar Prakash [3 ]
Dandekar, Manoj P. [2 ]
Shankaraiah, Nagula [1 ]
机构
[1] Natl Inst Pharmaceut Educ & Res NIPER, Dept Med Chem, Hyderabad 500037, India
[2] Natl Inst Pharmaceut Educ & Res NIPER, Dept Biol Sci Pharmacol & Toxicol, Hyderabad 500037, India
[3] Birla Inst Technol & Sci Pilani, Dept Pharm, Hyderabad Campus, Hyderabad 500078, India
关键词
Anticancer; Spirooxindoles; Benzimidazole; Tubulin polymerase inhibition; SAR (Structure activity relationship); CANCER; DISCOVERY;
D O I
10.1002/cmdc.202400052
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of spirocyclopropyl oxindoles with benzimidazole substitutions was synthesized and tested for their cytotoxicity against selected human cancer cells. Most of the molecules exhibited significant antiproliferative activity with compound 12 p being the most potent. It exhibited significant cytotoxicity against MCF-7 breast cancer cells (IC50 value 3.14 +/- 0.50 mu M), evidenced by the decrease in viable cells and increased apoptotic features during phase contrast microscopy, such as AO/EB, DAPI and DCFDA staining studies. Compound 12 p also inhibited cell migration in wound healing assay. Anticancer potential of 12 p was proved by the inhibition of tubulin polymerization with IC50 of 5.64 +/- 0.15 mu M. These results imply the potential of benzimidazole substituted spirocyclopropyl oxindoles, notably 12 p, as cytotoxic agent for the treatment of breast cancer. This study investigates the synthesis and in vitro cytotoxic potential of benzimidazole-substituted spirocyclopropyl oxindoles against diverse cancer cell lines. Notably, compound 12 p displays remarkable cytotoxicity against MCF-7 cells, exhibiting broad-spectrum efficacy across multiple tested cell lines. Additional microscopic examination confirms reduced cell viability and heightened apoptotic indicators, tubulin polymerase inhibition, suggesting promising cytotoxic agents for breast cancer therapy. image
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页数:13
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