In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers.

The growth inhibition of human cancer cells via T-type Ca(2+) channel blockade has been well known. Herein, a series of new 3,4-dihydroquinazoline derivatives were synthesized via a brief SAR study on KYS05090 template and evaluated for both T-type Ca(2+) channel (Cav3.1) blockade and cytotoxicity on three human ovarian cancer cells (SK-OV-3, A2780 and A2780-T).

T-type Ca2+ channel blocker, KYS05047 induces G1 phase cell cycle arrest by decreasing intracellular Ca2+ levels in human lung adenocarcinoma A549 cells.

In a previous study, we found that the 3,4-dihydroquinazoline derivative, 4-(Benzylcarbamoylmethyl)-2-(biphenyl-4-ylamino)-3-(5-tert-butyloxycarbamoyl-1-pentyl)-3,4-dihydroquinazoline (KYS05047), was a selective T-type Ca(2+) channel blocker with anti-proliferative effects against various cancer cells. However, the mechanism responsible for its effects has not been studied. In this study, we investigated the effect of KYS05047 on cell cycle arrest and the mechanisms involved in human lung adenocarcinoma A549 cells.

In vivo evaluation of oral anti-tumoral effect of 3,4-dihydroquinazoline derivative on solid tumor.

An extension of our previously reported 3,4-dihydroquinazoline derivative is investigated. Oral anti-tumoral activity of 3,4-dihydroquinazoline derivative (KYS05090) as potent and selective T-type calcium channel blocker was in vivo evaluated against A549 xenograft in BALB/c(nu/nu) nude mice. The rate of tumor volume increment in mouse model with KYS05090-treated group was remarkably slower than that of control group.