Indolyl-α-keto-1,3,4-oxadiazoles: Synthesis, anti-cell proliferation activity, and inhibition of tubulin polymerization.

Autor: Tantak MP; Department: Department of Chemistry Birla Institute of Technology and Science, Pilani 333 031, India., Malik M; Department: Department of Chemistry Birla Institute of Technology and Science, Pilani 333 031, India., Klingler L; Department: Department of Natural Sciences, University of Houston - Downtown, Houston, TX 77002, USA., Olson Z; Department: Department of Natural Sciences, University of Houston - Downtown, Houston, TX 77002, USA., Kumar A; Department: Department of Chemistry Birla Institute of Technology and Science, Pilani 333 031, India., Sadana R; Department: Department of Natural Sciences, University of Houston - Downtown, Houston, TX 77002, USA. Electronic address: sadanar@uhd.edu., Kumar D; Department: Department of Chemistry Birla Institute of Technology and Science, Pilani 333 031, India. Electronic address: dalipk@pilani.bits-pilani.ac.in.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2021 Apr 01; Vol. 37, pp. 127842. Date of Electronic Publication: 2021 Feb 05.
DOI: 10.1016/j.bmcl.2021.127842
Abstrakt: 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 IC 50 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 (IC 50  = 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.
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Databáze: MEDLINE
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