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ID: ALA1821554

Journal: Eur J Med Chem

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

Authors: Kamal A, Prabhakar S, Janaki Ramaiah M, Venkat Reddy P, Ratna Reddy Ch, Mallareddy A, Shankaraiah N, Lakshmi Narayan Reddy T, Pushpavalli SN, Pal-Bhadra M.

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.

CiteXplore: 21676506

DOI: 10.1016/j.ejmech.2011.05.050