A catalyst- and solvent-free multicomponent synthesis and docking study of some new antiproliferative N5-allyl-quinolylpyrido[2,3-b][1,4]benzodiazepinone precursors

Abstract

A multicomponent reaction has been developed by incorporating quinoline-3-carbaldehyde, 1,3-cyclohexanedione and 2,3-diaminopyridine into some new quinolylpyrido[2,3-b][1,4]benzodiazepinone assemblies under catalyst- and solvent-free conditions at 120 °C. Further reaction of the resulting intermediates with allyl bromide led to the formation of the corresponding N₅-allylated products, in situ, with higher yields in the same pot. Many candidates of this new class revealed noticeable activities against the representative human solid tumour cell lines A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast) and WiDr (colon). The most active compounds resemble the standard drug etoposide in antiproliferative activity against HeLa, T-47D and WiDr cell lines. Docking studies in the active site of MDM2 led us to consider this protein a plausible target for the antiproliferative effects of the compounds.