Synthesis and anticancer activity studies of indolylisoxazoline analogues. Issue 17 (15th September 2018)

• Record Type: Journal Article
• Authors: Chaitanya, M.V.S.K.; Reddy, P.O. Venkataramana; Nikhil, Kumar; Kumar, Anil; Shah, Kavita; Kumar, Dalip
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 17(2018)
• Page Start: 2842
• Page End: 2845
• Publication Date: 2018-09-15
• Subjects: Indolylisoxazolines -- Isoxazolines -- Indole heterocycles -- Anticancer activity -- Apoptosis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.07.035
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: A series of indolylisoxazolines were prepared and assessed for their cytotoxicity. Isoxazoline derivatives 6c –d, 6i and 6l displayed potent cytotoxicity (IC50 = 2.5–5.0 µM). Isoxazolines 6c and 6i induced apoptosis and inhibited C4-2 cell migration. Abstract: A new library of thirteen indolylisoxazolines 6a –m has been synthesized by the treatment of indolylchalcones with hydroxylamine hydrochloride. Evaluation of anticancer activity of indolylisoxazolines 6a –m led to the identification of potent compounds 6c –d, 6i and 6l, with IC50 ranging 2.5–5.0 µM against the tested cancer cell lines. Using a number of complementary techniques such as acridine orange/ethidium bromide staining, PARP1 cleavage and DNA strand breaks assay, we show that the compounds 6c and 6i induce apoptosis in highly aggressive C4-2 cells. Our data further revealed that 6c and 6i inhibited C4-2 cells proliferation without inducing reactive oxygen species (ROS). Finally, we show that compounds 6c and 6i also potently inhibit cell migration, indicating these compounds have the potential to serve as effective anti-cancer agents.