Researchers design hybrid molecules that show promise as cancer fighters
Scientists have synthesized a new class of benzimidazole-quinoline compounds and tested their ability to kill cancer cells. The work could accelerate drug discovery by providing a template for chemists to rapidly test variations of these hybrid molecules for therapeutic potential.
Originaltitel: Design, synthesis and anticancer activity of Novel benzimidazole containing quinoline hybrids
<p>In this work we present the synthesis of benzimidazole-quinoline hybrids series (<strong>9a-c </strong>and <strong>10a-f</strong>), characterized using spectroscopy studies (FT-IR, 1H NMR, and mass spectroscopy). The precursor for the hybrid compounds consists of two schemes: i. synthesis of substituted quinoline-4-carboxylic acids (<strong>3a-b</strong>) with various acetophenones. ii. The key intermediates (<strong>8a-c</strong>) were obtained initially from the benzimidazole-5-carboxylates (<strong>7a-c</strong>), were efficiently synthesized by 'one pot' nitro reductive cyclization reaction between ethyl 3-nitro-4-(substituted amino) benzoates <strong>6a-c</strong> and 5-bromothiophene-2-carbaldehyde. iii. Further, the benzimidazole esters (<strong>7a-c</strong>) were converted into the corresponding hydrazides (<strong>8a-c</strong>) and then finally obtained the benzimidazole-quinoline hybrids series (<strong>9a-c </strong>and <strong>10a-f</strong>). Compounds <strong>7a</strong> and<strong> 7b</strong> were crystallized and their molecular structures were determined using a single crystal X-ray diffraction method. The resultant compounds from the synthesis were screened (in-silico and in-vitro) for their anti-cancer activities (human melanoma cell line (A375) and human breast cancer cell line (MDA-MB-231)). The p53 receptor protein was used for the molecular docking analysis and compound (name) 10b binds the target site with four hydrogen bonds (-6.25 Kcal/mol). The antioxidant activity revealed compounds <strong>9a</strong> (IC50 = 604.8 mu g/mL) and 9b (IC50 = 604.8 mu g/mL 683.7 mu g/mL) to exhibit the highest percentage of inhibition and lowest IC50 value. In addition, compounds <strong>10a </strong>and <strong>10b </strong>showed high scavenging activity. The compounds 9a (A375: IC50 = 34.7 f 0.9 mu g/mL and MDA-MB-231: IC50 = 20.4 f 1.1 mu g/mL), <strong>10a</strong> (A375: IC50 = 19.6 f 1.3 mu g/mL and MDA-MB-231: IC50 = 37.0 f 1.3 mu g/mL) and <strong>10b</strong> (A375: IC50 = 16.5 f 1.5 mu g/mL and MDA-MB-231: IC50 = 13.4 f 1.5 mu g/mL) showed the significant cytotoxicity against these human cancer cell lines (melanoma and breast cancer) and can be potential anti-cancer molecules.</p>