Indolyl-α-keto-1,3,4-oxadiazoles: Synthesis, anti-cell proliferation activity, and inhibition of tubulin polymerization
Autor: | Dalip Kumar, Zachary Olson, Linus Klingler, Monika Malik, Anil Kumar, Mukund P. Tantak, Rachna Sadana |
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Rok vydání: | 2020 |
Předmět: |
Clinical Biochemistry
Pharmaceutical Science Antineoplastic Agents 01 natural sciences Biochemistry Jurkat cells Polymerization Structure-Activity Relationship Tubulin Cell Line Tumor Drug Discovery Humans Cytotoxicity Molecular Biology Cell Proliferation Oxadiazoles biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Cell growth Lymphoblast Organic Chemistry Molecular biology In vitro Tubulin Modulators 0104 chemical sciences 010404 medicinal & biomolecular chemistry Cell culture Cancer cell biology.protein Molecular Medicine Drug Screening Assays Antitumor |
Zdroj: | Bioorganicmedicinal chemistry letters. 37 |
ISSN: | 1464-3405 |
Popis: | A series of novel indolyl-α-keto-1,3,4-oxadiazole derivatives have been synthesized by employing molecular iodine-mediated oxidative cyclization of acylhydrazones. In vitro anti cell proliferation activity of these derivatives against various cancer cells lines such as human lymphoblast (U937), leukemia (Jurkat & SB) and human breast (BT474) was investigated. Among the synthesized indolyl-α-keto-1,3,4-oxadiazoles 19a-p, only one compound (19e) exhibited significant antiproliferative activity against a panel of cell lines. The compound 19e with 3,4,5-trimethoxyphenyl motif, endowed strong cytotoxicity against U937, Jurkat, BT474 and SB cancer cells with IC50 values of 7.1, 3.1, 4.1, and 0.8 µM, respectively. Molecular docking studies suggested a potential binding mode for 19e in the colchicine binding site of tubulin. When tested for in vitro tubulin polymerizaton, 19e inhibited tubulin polymezations (IC50 = 10.66 µM) and induced apoptosis through caspase 3/7 activation. Further, the derivative 19e did not cause necrosis when measured using lactate dehydrogenase assay. |
Databáze: | OpenAIRE |
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