Synthesis of some novel benzoxazole derivatives as anticancer, anti-HIV-1 and antimicrobial agents
Synthesis of some novel benzoxazole derivatives as anticancer, anti-HIV-1 and antimicrobial agents
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DOI：
10.1016/j.ejmech.2005.03.023
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发表时间：
2005-09-01
影响因子：
6.7
通讯作者：
Shalaby, MA
中科院分区：
文献类型：
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作者：
Rida, SM;Ashour, FA;Shalaby, MA
为了建立具有改进的抗HIV-1和抗微生物活性的新的候选物，我们在这里报道了各种系列的2-取代苯并恶唑的合成和体外生物学评价：2-[（芳基亚肼基、亚芳基、亚环烷基和N-取代的硫代氨基甲酰基）氰基甲基]-苯并恶唑（分别为2-4和7）; 2-[（4-或5-氧代噻唑烷-2-亚基）苯并恶唑（5和6）和2-（4-氨基-3-取代的-2-硫代-2，3-二氢噻唑-5-基）苯并恶唑（8），以及一些取代的3 H-吡啶并[2，1-B]苯并恶唑（9-11）。通过X射线晶体学测定化合物3b的绝对构象。体外抗肿瘤活性筛选结果表明，部分受试化合物具有广谱抗肿瘤活性。最具活性的化合物是2a、3b、8a和8d，它们的GI（50）MG-MID值：37.7、19.1、20.0和15.8 μ M; TGI MG-MID值：75.9、53.7、53.7和58.9 μ M; LC 50 MG-MID值：97.7、93.3、89。土地93.3亩。体外微生物学数据表明，化合物7 c对金黄色葡萄球菌（Staphylococcus aureus）最有活性（最小抑菌浓度（MIC）< 12.5 μ g/ml）。而化合物5、8a和8d对枯草芽孢杆菌的活性最高（MIC值< 12.5 μ g ml-1）。另一方面，化合物5和7 c对大肠杆菌的活性最高（MIC < 25 μ g ml（-1）），它们的活性约为氨苄青霉素和链霉素活性的一半。此外，化合物4 b和7 c对铜绿假单胞菌的活性最高（MIC < 25，50 μ g/ml）。化合物4 b的活性是氨苄青霉素和链霉素的两倍，而化合物7 c的活性是两者的两倍。抗真菌活性的结果表明，化合物7 c对白色念珠菌表现出温和的活性，与克霉唑相比（MIC < 100 μ g ml（-1））。体外HIV-1测试显示化合物7a显示出中等的抗HIV-1活性（最大%细胞保护，在2 × 10（-5）μ M时为36.6）。(c)2005年，Elsevier SAS。All rights reserved.
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.