Design, synthesis of phenstatin/isocombretastatin-oxindole conjugates as antimitotic agents. Issue 8 (15th April 2016)

• Record Type: Journal Article
• Authors: Kumar, G. Bharath; Nayak, V. Lakshma; Sayeed, Ibrahim Bin; Reddy, Vangala Santhosh; Shaik, Anver Basha; Mahesh, Rasala; Baig, Mirza Feroz; Shareef, Mohd Adil; Ravikumar, A.; Kamal, Ahmed
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 8(2016)
• Page Start: 1729
• Page End: 1740
• Publication Date: 2016-04-15
• Subjects: Phenstatin/isocombretastatin-oxindole -- Tubulin depolymerization -- Annexin V-FITC and mitochondrial membrane depolarization; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.02.047
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A series of phenstatin/isocombretastatin-oxindole conjugates was synthesized and tested for their cytotoxic activity against five human cancer cells such as prostate (DU-145), lung (A549), colon (HT-29), breast (MCF-7), liver (HepG2) cancer cells with IC50 values ranging from 0.049 to 38.90 μM. Amongst them, two conjugates (5c and5d ) showed broad spectrum of antiproliferative efficacy on lung cancer cells with an IC50 value of 79 nM and 93 nM, respectively, whereas on colon cancer cells with an IC50 values 45 nM and 49 nM, respectively. In addition, cell cycle assay revealed that these conjugates (5c and5d ) arrest at the G2 /M phase and leads to apoptotic cell death which was confirmed by Annexin V-FITC and mitochondrial membrane depolarization. Further, the tubulin polymerization assay analysis results suggest that these conjugates particularly5c and5d exhibit significant inhibitory effect on the tubulin assembly with an IC50 value of 1.23 μM and 1.01 μM, respectively. Molecular docking studies indicated that these compounds (5c and5d ) occupy the colchicine binding site of the tubulin.