R. Mohareb, N. S. Abbas, A. S. Abouzied
2019
Citations
0
Influential Citations
7
Citations
Quality indicators
Journal
Anti-cancer agents in medicinal chemistry
Abstract
BACKGROUND Dimedone and thiazole moieties are privileged scaffolds (acting as primary pharmacophores) in many compounds that are useful to treat several diseases, mainly tropical infectious diseases. Thiazole derivatives were well very important class of compounds due to their wide range of pharmaceutical and therapeutic activities. On the other, hand, dimedone was used to synthesis many therapeutically active compounds. Therefore, the combination of both moieties through a single molecule to produce heterocyclic compounds will produce excellent anticancer agents. OBJECTIVE The present work reports the synthesis of 48 new substances belonging to two classes of compounds: Dimedone and thiazoles, with the purpose of developing new drugs that present high specificity for tumor cells and low toxicity to the organism. To achieve this goal, our strategy was to synthesize a series of 4,5,6,7-tetrahydrobenzo[d]-thiazol-2-yl derivatives using reaction of the 2-bromodimedone with cyanothioacetamide. METHOD The reaction of 2-bromodimedone with cyanothioacetamide gave the 4,5,6,7-tetrahydrobenzo[d]-thiazol-2-yl derivative 3. The reactivity of compound 3 towards some chemical reagents were studied to produce different heterocyclic derivatives. RESULTS A cytotoxic screening was performed to evaluate the performance of the new derivatives in six tumor cell lines. Thirteen compounds were shown to be promising toward the tumor cell lines were further evaluated toward five tyrosine kinase. CONCLUSION The results of antitumor screening showed that many of the tested compounds were of high inhibition towards the tested cell lines. Compounds 6c, 8c, 11d, 13b, 15g, 20d and 21d were the most potent compounds toward c-Met kinase and PC-3 cell line. The most promising compounds 6c, 8c, 11b, 11d, 13b, 14b, 15c, 15g, 20c, 20d, 21b, 21c and 21d were further investigated against tyrosine kinase (c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR). Compounds 6c, 11b, 11d, 14b, 15c, and 20d were selected to examine their Pim-1 kinase inhibition activity the results revealed that compounds 11b, 11d and 15c of high activities.