Jang, Sun Jeong Choi, Heung Woo Choi, Doo Li Cho, Sehyeon Rim, Hong-Kun Choi, Hye-Eun Kim, Ki-Sun Huang, Minghua Rhim, Hyewhon Lee, Kyung-Tae Lee, Jae Yeol 2024-01-20T11:00:58Z 2024-01-20T11:00:58Z 2021-09-05 2013-12-15 0960-894X https://pubs.kist.re.kr/handle/201004/127326 The growth inhibition of human cancer cells via T-type Ca2+ 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 Ca2+ channel (Ca(v)3.1) blockade and cytotoxicity on three human ovarian cancer cells (SK-OV-3, A2780 and A2780-T). Most of compounds except 6i generally exhibited more potent cytotoxicity on SK-OV-3 than mibefradil as a positive control regardless of the degree of T-type channel blockade. In particular, eight compounds (KYS05090, 6a and 6c-6h) showing strong channel blockade exhibited almost equal and more potent cytotoxicity on A2780 when compared to mibefradil. On A2780-T paclitaxel-resistant human ovarian carcinoma, two compounds (KYS05090 and 6d) were 20-fold more active than mibefradil. With respect to cell cycle arrest effect on A2780 and A2780-T cells, KYS05090 induced large proportion of sub-G(1) phase in the cell cycle progression of A2780 and A2780-T, meaning the induction of cancer cell death instead of cell cycle arrest via blocking T-type Ca2+ channel. Among new analogues, compounds 6g and 6h induced cell cycle arrest at G(1) phase of A2780 and A2780-T cells in dose-dependent manner and exhibited strong anti-proliferation effects of ovarian cancer cells by blocking T-type Ca2+ channel. Furthermore, 6g and 6h possessing strong cytotoxic effects could induce apoptosis of A2780 cells, which was detected by confocal micrographs using DAPI staining. (C) 2013 Elsevier Ltd. All rights reserved. English Pergamon Press Ltd. PROLIFERATION CYCLE EXPRESSION ISOFORMS SUBUNIT GLIOMA TUMOR In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers Article 10.1016/j.bmcl.2013.10.049 1 Bioorganic & Medicinal Chemistry Letters, v.23, no.24, pp.6656 - 6662 Bioorganic & Medicinal Chemistry Letters 23 24 6656 6662 scie scopus 000327787700025 2-s2.0-84888875574 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article PROLIFERATION CYCLE EXPRESSION ISOFORMS SUBUNIT GLIOMA TUMOR T-type Ca2+ channel Ovarian cancer Cytotoxicity Cell cycle arrest Apoptosis