Design, synthesis and biological evaluation of novel 6-substituted pyrrolo [3,2-d] pyrimidine analogues as antifolate antitumor agents

Add time:07/13/2019    Source:sciencedirect.com

A series of novel 6-substituted pyrrolo[3,2-d]pyrimidine analogues (10a, 11a-13a, 15a, 17a, 18a, 27a and 28a) have been designed and synthesized as antifolate antitumor agents. The anti-proliferative activities of these compounds against HL60, A549, H1299, Hela, HCT116 and HT29 tumor cells were evaluated. Most of the compounds exhibited micromolar anti-proliferative potencies. Compound 15a, the most potent one, has GI50 value of 0.73, 1.72, and 8.92 μM against A549, H1299 and HL60 cells, respectively. The cell cycle distribution assay displayed that 15a could increase the accumulation of G2/M-phase cells. 15a showed low potency in induction of apoptosis. However, the inhibition of A549 cell colony formation was observed. These indicated that the tumor cell death relied on the irreversible effect of 15a on clonogenicity and cell proliferation. The identification of targeted pathway of 15a implied that the anti-proliferative potencies of 15a probably act through dual inhibition of thymidylate synthase (TS) and dihydrofolate reductase (DHFR).

We also recommend Trading Suppliers and Manufacturers of ethyl 4-chloro-5-methyl-5h-pyrrolo[3,2-d]pyrimidine-7-carboxylate (cas 1234616-53-5). Pls Click Website Link as below: cas 1234616-53-5 suppliers

Prev:Design, synthesis and biological evaluation of novel, orally bioavailable pyrimidine-fused heterocycles as influenza PB2 inhibitors
Next:Discovery of 2-substituted-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamide as potent and selective protein arginine methyltransferases 5 inhibitors: Design, synthesis and biological evaluation)