2. Academic Validation
  3. Design and synthesis of pyrazole-oxindole conjugates targeting tubulin polymerization as new anticancer agents

Design and synthesis of pyrazole-oxindole conjugates targeting tubulin polymerization as new anticancer agents

  • Eur J Med Chem. 2015 Mar 6:92:501-13. doi: 10.1016/j.ejmech.2013.10.077.
Ahmed Kamal 1,  Anver Basha Shaik 2,  Nishant Jain 3,  Chandan Kishor 3,  Ananthamurthy Nagabhushana 4,  Bhukya Supriya 3,  G Bharath Kumar 2,  Sumit S Chourasiya 2,  Yerramsetty Suresh 3,  Rakesh K Mishra 5,  Anthony Addlagatta 6
Affiliations

Affiliations

  • 1 Medicinal Chemistry and Pharmacology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: ahmedkamal@iict.res.in.
  • 2 Medicinal Chemistry and Pharmacology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 3 Centre for Chemical Biology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 4 CSIR - Centre for Cellular and Molecular Biology, Hyderabad 500007, India; CoE in Epigenetics, IISER-Pune, Pune 411021, India.
  • 5 CSIR - Centre for Cellular and Molecular Biology, Hyderabad 500007, India.
  • 6 Centre for Chemical Biology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: anthony@iict.res.in.
PMID: 25599948 DOI: 10.1016/j.ejmech.2013.10.077
Abstract

A series of twenty one compounds with pyrazole and oxindole conjugates were synthesized by Knoevenagel condensation and investigated for their antiproliferative activity on different human Cancer cell lines. The conjugates are comprised of a four ring scaffold; the structural isomers 12b and 12c possess chloro-substitution in the D ring. Among the congeners 12b, 12c, and 12d manifested significant cytotoxicity and inhibited tubulin assembly. Treatments with 12b, 12c and 12d resulted in accumulation of cells in G2/M phase, disruption of microtubule network, and increase in cyclin B1 protein. Zebrafish screening revealed that 12b, and 12d caused developmental defects. Docking analysis demonstrated that the congeners occupy the colchicine binding pocket of tubulin.

Keywords

Pyrazole–oxindole conjugates; Tubulin depolymerization; Zebrafish screening and molecular modeling.

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