Synthesis of some novel benzoxazole derivatives as anticancer, anti-HIV-1 and antimicrobial agents

In an effort to establish new candidates with improved antineoplastic, anti-HIV-1 and antimicrobial activities we report here the synthesis and in vitro biological evaluation of various series of 2-substituted benzoxazoles: 2-[(Arylhydrazono, arylidene, cycloalkylidene and N-substituted thiocarbamoyl)cyanomethyl]-benzoxazoles(2-4 and 7, respectively); 2-[(4- or 5-oxothiazoliden-2-yliden)benzoxazoles (5 and 6) and 2- (4-amino-3-substituted-2-thioxo-2,3-dihydrothiazol-5-yl)benzoxazoles (8), together with the synthesis of some substituted 3H-pyrido[2,1-b]benzoxazoles (9-11). The absolute contiguration of compound 3b was determined by X-ray crystallography. The results of the in vitro anticancer screening revealed that some of the tested compounds exhibited broad spectrum antitumor activity. The most active compounds are 2a, 3b, 8a and 8d, their GI(50) MG-MID values: 37.7, 19.1, 20.0 and 15.8 mu M; TGI MG-MID values: 75.9, 53.7, 53.7, and 58.9 mu M; and LC50 MG-MID values: 97.7, 93.3, 89. land 93.3 mu M, respectively. The in vitro microbiological data showed that compound 7c was the most active against Staphylococcus aureus (minimal inhibitory concentration (MIC) < 12.5 mu g ml(-1)). While compounds 5, 8a, and 8d were the most active against Bacillus subtilis (MIC values < 12.5 mu g ml-1). On the other hand, compounds 5 and 7c were the most active against Escherichia coli (MIC < 25 mu g ml(-1)), their activity is about half the activity of ampicillin and streptomycin. In addition, compound 4b and 7c were the most active against Pseudomonas aeruginosa (MIC < 25, 50 mu g ml(-1)). Compound 4b was two times as active as ampicillin and streptomycin while compound 7c was active as both. The results of antimycotic activity indicated that, Compound 7c showed mild activity against Candida albicans when compared with clotrimazole (MIC < 100 mu g ml(-1)). In vitro HIV-1 testing revealed that compound 7a displayed moderate anti-HIV-1 activity (maximum % cell protection, 36.6 at 2 x 10(-5) mu M). (c) 2005 Elsevier SAS. All rights reserved.