Naini Raju, Ravikumar Eslavath, Singh Surya S, Kancha Rama K, Rao Khareedu V, Reddy Vudem D
CPMB, Osmania University, Hyderabad, 500007. India.
Department of Biochemistry, Osmania University, Hyderabad. India.
Anticancer Agents Med Chem. 2017 Nov 24;17(11):1537-1544. doi: 10.2174/1871520617666170327122929.
Resveratrol (RV) and its analogues Aza-stilbenes were found effective in exhibiting anticancer activity.
The present study mainly focused on the green synthesis of novel imine stilbene analogues and evaluation of their anticancer activity besides their influence on hypoxia-induced gene expression in cancer cells.
Novel imine stilbenes, differing in number and/or position of hydroxyl and methoxy functional groups, have been synthesized using green chemistry mediated condensation reaction between aldehydes and amines in the ethanolic extract of Psoralea corylifolia hairy roots and tested for their anticancer potential.
Ethanol containing 1% hairy root extract facilitated instant reaction and yielded more than 99% product( s). MTT assay on HeLa cells treated with imine stilbene analogues revealed an increase in the inhibition of cell proliferation as compared to RV. Treatment of nontumor HEK293 cells with these compounds disclosed minimal toxicity implying the selective advantage of these compounds for cervical cancer therapy. Scratch assay on HeLa cells displayed inhibition of directional cell motility by these analogues and compound 3e [4-((E)-(4- hydroxyphenylimino)methyl)-2-methoxyphenol] recorded maximum inhibition. In reporter assay, as compared to untreated N-(2-Methoxy-2-oxoacetyl) glycine methyl ester (DMOG) induced cells, hypoxia response element- directed transcriptional activity has been significantly reduced in DMOG induced cells treated with imine stilbene analogues.
Overall results indicated that four of the five imine stilbene analogues exhibited enhanced anticancer activity than that of the RV. As such, the novel synthetic compounds 3d, 3e and 3b endowed with potent anticancer activity than RV can serve as drug lead molecules.
白藜芦醇（RV）及其类似物氮杂芪被发现具有抗癌活性。
本研究主要聚焦于新型亚胺芪类似物的绿色合成，评估其抗癌活性以及对癌细胞缺氧诱导基因表达的影响。
利用绿色化学介导的补骨脂毛状根乙醇提取物中醛与胺之间的缩合反应，合成了羟基和甲氧基官能团数量和/或位置不同的新型亚胺芪，并测试了它们的抗癌潜力。
含1%毛状根提取物的乙醇促进了即时反应，产物产率超过99%。用亚胺芪类似物处理HeLa细胞的MTT试验表明，与RV相比，细胞增殖抑制作用增强。用这些化合物处理非肿瘤性HEK293细胞显示出最小的毒性，这意味着这些化合物对宫颈癌治疗具有选择性优势。对HeLa细胞进行划痕试验显示，这些类似物抑制了细胞的定向运动，化合物3e[4-((E)-(4-羟基苯基亚氨基)甲基)-2-甲氧基苯酚]的抑制作用最大。在报告基因试验中，与未处理的N-(2-甲氧基-2-氧代乙酰基)甘氨酸甲酯（DMOG）诱导的细胞相比，用亚胺芪类似物处理的DMOG诱导细胞中缺氧反应元件指导的转录活性显著降低。
总体结果表明，五种亚胺芪类似物中的四种表现出比RV更强的抗癌活性。因此，具有比RV更强抗癌活性的新型合成化合物3d、3e和3b可作为药物先导分子。
