Student Research Committee, Pharmaceutical Sciences Research Center, Department of Medicinal Chemistry, Mazandaran University of Medical Sciences, Sari, Iran.
Pharmaceutical Sciences Research Center, Department of Medicinal Chemistry, Mazandaran University of Medical Sciences, Sari, Iran.
Spectrochim Acta A Mol Biomol Spectrosc. 2018 Apr 5;194:21-35. doi: 10.1016/j.saa.2017.12.063. Epub 2017 Dec 29.
In a search for novel antiproliferative agents, a series of quinoxaline derivatives containing 2-aminoimidazole (8a-8x) were designed and synthesized. The structures of synthesized compounds were confirmed by IR, H NMR, C NMR, Mass Spectroscopy and analyzed using HSQC, COSY, ROESY, HMBC techniques. The anticancer activity of all derivatives were evaluated for colon cancer and breast cancer cell lines by the MTT assay and acridine orange/ethidium bromide double staining method. The anti-cancer effect in human colon cancer (HCT-116) and breast cancer (MCF-7) cell lines exhibited that compounds 8a, 8s, 8t, 8w, 8x appeared as potent antiproliferative agents and especially inhibited the human colon cancer cell proliferation with percentage of inhibition by over 50%. The most active compound was (E)-4-phenyl-1-((quinoxalin-2-ylmethylene)amino)-1H-imidazol-2-amine (8a) with the highest inhibition for MCF-7 (83.3%) and HCT-116 (70%) cell lines after 48 and 24h, respectively. Molecular docking studies of these derivatives within c-kit active site as a validated target might be suggested them as appropriate candidates for further efforts toward more potent anticancer compounds.
在寻找新型抗增殖剂的过程中，设计并合成了一系列含有 2-氨基咪唑的喹喔啉衍生物（8a-8x）。通过红外光谱（IR）、核磁共振氢谱（1H NMR）、核磁共振碳谱（13C NMR）、质谱（MS）对合成化合物的结构进行了确认，并通过 HSQC、COSY、ROESY 和 HMBC 技术对其进行了分析。采用 MTT 法和吖啶橙/溴化乙锭双重染色法，评估了所有衍生物对结肠癌和乳腺癌细胞系的抗癌活性。在人结肠癌（HCT-116）和乳腺癌（MCF-7）细胞系中的抗癌作用表明，化合物 8a、8s、8t、8w 和 8x 表现出很强的抗增殖活性，特别是对人结肠癌细胞的增殖抑制率超过 50%。最活跃的化合物是（E）-4-苯基-1-（喹喔啉-2-亚甲基）氨基-1H-咪唑-2-胺（8a），在 48 和 24h 后，对 MCF-7（83.3%）和 HCT-116（70%）细胞系的抑制作用最高。这些衍生物在 c-kit 活性部位的分子对接研究可能表明它们是进一步开发更有效的抗癌化合物的合适候选物。
