Biological evaluation and pharmacophore modeling of some benzoxazoles and their possible metabolites

Abstract

A series of benzoxazole derivatives and some possible primary metabolites were evaluated as anticancer agents. In vitro anti-proliferative activities of the compounds were tested using the SRB assay on cancerous (HeLa) and non-cancerous (L929) cell lines. It was found that 17 of 21 tested compounds had cytotoxic activity on HeLa cells and the cytotoxic activities of the compounds were 15-700 times higher than on L929 cells. We generated two distinct pharmacophore models for the cytotoxic activities of the compounds on HeLa and L929 cells. While active compounds such as camptothecin and X8 fitted the two models generated for both cell lines, selective cytotoxic compounds such as XT3B fitted only the model generated for HeLa cells. Evaluation of the genotoxic activities of the cytotoxic compounds with the alkaline comet assay revealed that compounds X17 and XT3 showed strong genotoxic effects against HeLa cells at low concentrations whereas they had no genotoxic effect on L929 cells. Due to the selective ability for inducing DNA strand breaks only on cancerous cells, the compounds were identified as effective derivatives for anticancer candidates.

Bazı Yeni Benzoksazol Türevlerinin Sentezi ve Antimikrobiyal ve Sitotoksik Aktivite Çalışmaları

“…This approach further increases the interest in benzoxazole derivatives (Oehlers et al, 2004). The investigations reveal that benzoxazole and its analogs are compounds that give meaningful results in terms of microbiological (Taşcı et al, 2018) and cytotoxic activity (Zilifdar et al, 2018). Benzoxazole ring system also has a broad spectrum of pharmacological effects such as anti-inflammatory (Sondhi et al, 2006), antiepileptic (Wei et al, 2009), antialzheimer (Celik et al, 2020;Temiz-Arpaci et al, 2016), anti-HIV (Sakamoto et al, 2007), topoisomerase inhibitors (Oksuzoglu et al, 2008), kinase inhibitors (Han et al, 2012), protease inhibitors (Jonckers et al, 2012).…”

Unexpected Rearrangement Reaction and Synthesis of Benzoxazoles

“…研究表明氮杂环化合物具有多种生物活性 [2～5] , 例如显 著的抑菌活性 [6] , 还具有抗病毒 [7,8] 、抗癌 [9,10] 、抗炎 [11] 、 镇痛 [12,13] 等作用. 其各类衍生物在农用化学品、天然产 物、功能材料 [14] 和药物活性分子中应用也十分广泛 [15] , 例如以氮杂环化合物为起始原料可以合成荧光增白 剂 [16] , 作为配体和金属组成配合物 [17] 等; 在医药上, 大 量的氮杂环化合物已经作为药物 [18] 或候选物应用于临 床来治疗各种类型的疾病, 具有广阔的发展前景和应用 价值.…”