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

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.

A series of new chalcone-pyrrolobenzodiazepine conjugates connected through a 1,2,3-triazole containing alkane spacers has been synthesized and evaluated for their in vitro anticancer activity (<0.1–2.92 μM) on selected human cancer cell lines.Figure optionsDownload as PowerPoint slideHighlights
► New chalcone linked PBD conjugates with significant anticancer activity.
► ‘Click’ chemistry protocol has been utilized. G1 cell cycle arrest in MCF-7 cell line.
► Down regulation of cyclin D1 and Cdk4 have observed.
► Down regulation of NF-kB, Bcl-xL and Bcl2 were also observed.