Abstract A68: Design, synthesis, and antiproliferative evaluations of 3-phenylquinolinylchalcone derivatives against non-small cell lung cancers and breast cancers

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Abstract Chalcones are natural products which have displayed a wide variety of biological activities, including anti-malarial, anti-protozoal, anti-inflammatory, immunomodulatory, nitric oxide inhibition, tyronase inhibition, and anticancer activities. Due to their abundance in plants and ease of synthesis, the chalcone class of compounds has attracted extensive studies. On the other hand, quinoline skeleton is one of the key building elements for a large number of natural and synthetic heterocycles which possess a wide variety of biological effects such as antimalarials, bactericidal, antitumor, anti-inflammatory, antiproliferative, and antiviral activities. Therefore, a series of chalcone derivatives in which an aryl moiety was replaced with quinoline nucleus have been synthesized and evaluated for their antiproliferative activities. These newly synthesized chalcone derivatives were evaluated in vitro against a panel of six cancer cell lines including three non-small cell lung cancer cells (H1299, H460, and A549), three breast cancer cells (MCF-7, MDA-MB-231, and SKBR-3), and a normal mammary epithelial cell (M10), Among them, (E)-1-(5-bromothiophen-2-yl)-3-(3-(4-methoxyphenyl)quinolin-2-yl)prop-2-en-1-one (1) was active against the growth of H1299 and SKBR-3 with IC50 values of 0.71 and 0.52 μM respectively which was more active than the positive topotecan (IC50 values of > 10.0 μM in each case). Compound 1 was the most active against the growth of MDA-MB-231 with an IC50 value of < 0.1 μM and was not cytotoxic to the normal mammary epithelial cell (M10) with an IC50 value of 9.38 μM. Mechanism studies indicated that compound 1 induced cell cycle arrest at G2/M phase followed by DNA fragmentation via activation of caspase-3, cleavage of PARP, and consequently caused the cell death. Further structural optimization is currently ongoing. Citation Format: Cherng-Chyi Tzeng, Chih-Hua Tseng, Yeh-Long Chen. Design, synthesis, and antiproliferative evaluations of 3-phenylquinolinylchalcone derivatives against non-small cell lung cancers and breast cancers. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A68.