synthesis and biological evaluation of 3-substituted-indolin-2-one derivatives containing chloropyrrole moieties合成和生物评价包含chloropyrrole根3-substituted-indolin-2-one衍生品.pdf

Molecules 2011, 16, 9368-9385; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis and Biological Evaluation of 3-Substituted-indolin-2- one Derivatives Containing Chloropyrrole Moieties Yun-Zhou Jin 1, Da-Xu Fu 1, Nan Ma 1, Zhan-Cheng Li 1, Quan-Hai Liu 2, Lin Xiao 2 and Rong-Hua Zhang 1,* 1 Department of Chemistry, Tongji University, Shanghai, 200092, China 2 Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, Shanghai, 200434, China * Author to whom correspondence should be addressed; E-Mail: tj_zrh@163.com; Tel.: +86-0218542. Received: 10 October2011; in revised form: 3 November 2011 / Accepted: 3 November 2011 / Published: 8 November 2011 Abstract: Eighteen novel 3-substituted-indolin-2-ones containing chloropyrroles were synthesized and their biological activities were evaluated. The presence of a chlorine atom on the pyrrole ring was crucial to reduce cardiotoxicity. The presence of a 2-(ethyl- amino)ethylcarbamoyl group as a substituent at the C-4′ position of the pyrrole enhanced the antitumor activities notably. IC50 values as low as 0.32, 0.67, 1.19 and 1.22 µM were achieved against non-small cell lung cancer (A549), oral epithelial (KB), melanoma (K111) and large cell lung cancer cell lines (NCI-H460), respectively. Keywords: antitumor activities; indolin-2-one; chloropyrrole; synthesis 1. Introduction Angiogenesis, an important physiological process of new capillary blood vessel forma