Synthesis of 4-phenyl-5,6-dihydrobenzo[h]quinazolines and their evaluation as growth inhibitors of carcinoma cells

Article abstract of DOI:10.1039/c5ra24429c

The synthesis of various benzo[h]quinazoline analogs (4a-f, 6a-d, 8a and 8b) was accomplished through the reaction of chalcone with guanidine. The synthesized compounds (4a-f, 6a-d, 8a and 8b) were screened for their anticancer potential against different cancer cells viz MCF-7, DLD1, A549, DU145 & FaDu cell lines. Compounds 4a, 6a-d & 8b showed significant anticancer activity in these cancer cell lines with a range of IC₅₀ values of 1.5-12.99 μM. A functional study of promising molecule 6d at 7 μM (at the IC₅₀ value) over 24 and 48 h showed that it possesses anticancer activity through triggering apoptosis. In a tubulin polymerization assay, 6d effectively inhibited tubulin polymerization with an IC₅₀ of 2.27 μM. In silico docking studies of 6d revealed that 6d has good affinity with an estrogen receptor as well as a tubulin protein on its β-sheet of the colchicines binding site.