Synthesis and evaluation of 4/5-hydroxy-2,3-diaryl(substituted)-cyclopent-2-en-1-ones as cis-restricted analogues of combretastatin A-4 as novel anticancer agents. Academic Article uri icon


  • A new series of 2,3-diaryl-4/5-hydroxy-cyclopent-2-en-1-one analogues replacing the cis double bond of combretastatin A-4 (CA-4) by 4/5-hydroxy cyclopentenone moieties was designed and synthesized. The analogues displayed potent cytotoxic activity (IC50<1 microg/mL) against a panel of human cancer cell lines and endothelial cells. The most potent analogues 11 and 42 belonging to the 5-hydroxy cyclopentenone class were further evaluated for their mechanism of action. Both of the analogues led to cell cycle arrest at G2/M phase and induced apoptosis in endothelial cells. Antitubulin property of 42 was superior to 11 and comparable to CA-4. The compound 42 had better aqueous solubility, metabolic stability, and pharmacokinetic profile than CA-4 and also demonstrated significant tumor regression in the human colon xenograft model. Our data suggests that cis-restricted analogues of CA-4 are a new class of molecules that have the potential to be developed as novel agents for the treatment of cancer.

published proceedings

  • J Med Chem

altmetric score

  • 3

author list (cited authors)

  • Gurjar, M. K., Wakharkar, R. D., Singh, A. T., Jaggi, M., Borate, H. B., Shinde, P. D., ... Burman, A. C.

citation count

  • 31

complete list of authors

  • Gurjar, Mukund K||Wakharkar, Radhika D||Singh, Anu T||Jaggi, Manu||Borate, Hanumant B||Shinde, Popat D||Verma, Ritu||Rajendran, Praveen||Dutt, Sarjana||Singh, Gurvinder||Sanna, Vinod K||Singh, Manoj K||Srivastava, Sanjay K||Mahajan, Vishal A||Jadhav, Vinod H||Dutta, Kakali||Krishnan, Karthik||Chaudhary, Anika||Agarwal, Shiv K||Mukherjee, Rama||Burman, Anand C

publication date

  • April 2007