2. Academic Validation
  3. Synthesis and anticancer activity of chalcone-pyrrolobenzodiazepine conjugates linked via 1,2,3-triazole ring side-armed with alkane spacers

Synthesis and anticancer activity of chalcone-pyrrolobenzodiazepine conjugates linked via 1,2,3-triazole ring side-armed with alkane spacers

  • Eur J Med Chem. 2011 Sep;46(9):3820-31. doi: 10.1016/j.ejmech.2011.05.050.
Ahmed Kamal 1,  S Prabhakar,  M Janaki Ramaiah,  P Venkat Reddy,  Ch Ratna Reddy,  A Mallareddy,  Nagula Shankaraiah,  T Lakshmi Narayan Reddy,  S N C V L Pushpavalli,  Manika Pal-Bhadra
Affiliations

Affiliation

  • 1 Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India. ahmedkamal@iict.res.in
PMID: 21676506 DOI: 10.1016/j.ejmech.2011.05.050
Abstract

Aiming to develop multitarget drugs for the Anticancer treatment, a new class of chalcone-pyrrolo[2,1-c] [1,4]benzodiazepine (PBD) conjugates linked through a 1,2,3-triazole moiety containing alkane spacers has been designed and synthesized. Combining these two core pharmacophore structures with modifications at A-C8/C-C2-position of PBD ring system yielded analogs with improved efficacy and have shown promising in vitro Anticancer activity ranging from <0.1-2.92 μM. These PBD-conjugates caused G1 cell cycle arrest with effect on G1 cell cycle regulatory proteins such as Cyclin D1 and CDK4. These conjugates also exhibited inhibitory effect on NF-kB, Bcl-xL proteins that play a vital role in breast Cancer cell proliferation. These findings suggest that one of the compound 4d among this series is most effective and has potential for detailed investigations.

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