Design, Synthesis, and Anti-Cancer Evaluation of some Novel Leucettamine B Analouges

Objective: Novel anticancer agents were designed to be synthesized considering Leucettamine B as a lead compound. Leucettamine B, which was isolated from a marine sponge, is a tyrosine-regulated inhibitor of kinase 1A (Dyrk1A), andhas gained a lot of attention as a pharmacological target in malignant brain tumors. Method: 3-Phenyl-2-thioxoimidazolidin-4-one 1 has been used for the synthesis of various fused phenylimidazo[1,2-f]pyrimidine 4, phenylimidazo[2,1-b]quinazoline 6, phenylimidazo[1,2-b][1,2,4]triazine 10-14, 20 and 21 as well asimidazo[1,2-b][1,2,4]triazepine analogues 15 and 17 through different chemical reactions. Results: Considering that eleven of the synthesized compounds were selected for evaluation of their anticancer activity by the National Cancer Institute (NCI), U.S.A. The anticancer evaluation was carried out against National Cancer Institute )NCI) cell lines using single high dose. Conclusion: Compounds 8-(4-Methoxybenzylidene)-2,4-diamino-5-phenyl-5H-imidazo[1,2-b][1,2,4,6] tetrazepin-7(8H)-one 16, 20 and 24 were found to have selective potent anticancer activity against Non-Small Cell Lung cancer EKVX, Melanoma UACC-62 and Breast cancer HS 578T cell lines.