2. Academic Validation
  3. Design, synthesis of phenstatin/isocombretastatin-oxindole conjugates as antimitotic agents

Design, synthesis of phenstatin/isocombretastatin-oxindole conjugates as antimitotic agents

  • Bioorg Med Chem. 2016 Apr 15;24(8):1729-40. doi: 10.1016/j.bmc.2016.02.047.
G Bharath Kumar 1,  V Lakshma Nayak 1,  Ibrahim Bin Sayeed 1,  Vangala Santhosh Reddy 1,  Anver Basha Shaik 1,  Rasala Mahesh 1,  Mirza Feroz Baig 1,  Mohd Adil Shareef 1,  A Ravikumar 2,  Ahmed Kamal 3
Affiliations

Affiliations

  • 1 Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
  • 2 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 3 Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India; Catalytic Chemistry Chair, Chemistry Department College of Science, King Saud University, Riyadh, Saudi Arabia. Electronic address: ahmedkamal@iict.res.in.
PMID: 26970659 DOI: 10.1016/j.bmc.2016.02.047
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 and 5d) 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 and 5d) 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 particularly 5c and 5d 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 and 5d) occupy the colchicine binding site of the tubulin.

Keywords

Annexin V-FITC and mitochondrial membrane depolarization; Phenstatin/isocombretastatin-oxindole; Tubulin depolymerization.

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