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

2011; Elsevier BV; Volume: 46; Issue: 9 Linguagem: Inglês

10.1016/j.ejmech.2011.05.050

1768-3254

Ahmed Kamal, S. Prabhakar, M. Janaki Ramaiah, P. Venkat Reddy, Ch. Ratna Reddy, Adla Mallareddy, Nagula Shankaraiah, T. Lakshmi Narayan Reddy, S. N. C. V. L. Pushpavalli, Manika Pal‐Bhadra,

Synthesis and Biological Evaluation

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.