2. Academic Validation
  3. Design, synthesis and biological evaluation of 3,5-diaryl-isoxazoline/isoxazole-pyrrolobenzodiazepine conjugates as potential anticancer agents

Design, synthesis and biological evaluation of 3,5-diaryl-isoxazoline/isoxazole-pyrrolobenzodiazepine conjugates as potential anticancer agents

  • Eur J Med Chem. 2010 Sep;45(9):3924-37. doi: 10.1016/j.ejmech.2010.05.047.
Ahmed Kamal 1,  J Surendranadha Reddy,  M Janaki Ramaiah,  D Dastagiri,  E Vijaya Bharathi,  M Ameruddin Azhar,  Farheen Sultana,  S N C V L Pushpavalli,  Manika Pal-Bhadra,  Aarti Juvekar,  Subrata Sen,  Surekha Zingde
Affiliations

Affiliation

  • 1 Division of Organic Chemistry, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India. ahmedkamal@iict.res.in
PMID: 20557981 DOI: 10.1016/j.ejmech.2010.05.047
Abstract

A series of 3,5-diaryl-isoxazoline/isoxazole linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates were prepared. These conjugates showed potent Anticancer activity with GI(50) values in the range of <0.1-3.6 microM. Some of these PBD conjugates (6a-c) with promising Anticancer activity were further investigated on the cell cycle distribution. Moreover, these PBD conjugates exhibited G0/G1 arrest, enhancement in the levels of p53 protein as well as mitochondrial-mediated intrinsic pathway, leading to release of cytochrome c, activation of Caspase-3, cleavage of PARP and subsequent apoptotic cell death. Hence these PBD conjugates with 6a being the most potent one could be be taken up for preclinical studies either alone or in combination with existing therapies.

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