novel benzothiazole, benzimidazole and benzoxazole derivatives as potential antitumor agents synthesis and preliminary in vitro biological evaluation新型苯并噻唑、苯并咪唑和苯并恶唑衍生物作为潜在的抗肿瘤药物体外生物合成和初步评价.pdfVIP

Molecules 2012, 17, 873-883; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Novel Benzothiazole, Benzimidazole and Benzoxazole Derivatives as Potential Antitumor Agents: Synthesis and Preliminary in Vitro Biological Evaluation Pu Xiang †, Tian Zhou †, Liang Wang, Chang-Yan Sun, Jing Hu, Ying-Lan Zhao * and Li Yang * State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicinal School, Sichuan University, Chengdu 610041, Sichuan, China † These authors contributed equally to this work. * Authors to whom correspondence should be addressed; E-Mails: Alancenxb@ (Y.-L.Z.); yangli@ (L.Y.); Tel.: +86-28-8550-3628; Fax: +86-28-8550-3628. Received: 12 December 2011; in revised form: 6 January 2012 / Accepted: 10 January 2012 / Published: 17 January 2012 Abstract: In a previous hit-to-lead research program targeting anticancer agents, two promising lead compounds, 1a and 1b, were found. However, the poor solubility of 1a and 1b made difficult further in vivo studies. To solve this problem, a lead optimization was conducted through introducing N-methyl-piperazine groups at the 2-position and 6-position. To our delight, the optimized analogue 1d showed comparable antiproliferative activity in vitro with better solubility, compared with 1a. Based on this result, the replacement of the benzothiazole scaffold with benzimidazole and benzoxazole moieties afforded 1f and 1g, whose activities