Vyas Vivek K, Variya Bhavesh, Ghate Manjunath D
Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.
Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.
Eur J Med Chem. 2014 Jul 23;82:385-93. doi: 10.1016/j.ejmech.2014.05.064. Epub 2014 May 27.
In continuation of our research for novel human dihydroorotate dehydrogenase (hDHODH) inhibitors, herein we reported design, synthesis and pharmacological evaluation of novel substituted quinoline-2-carboxamide derivatives. Human DHODH enzyme inhibition assay was used to screen the synthesized compounds as hDHODH inhibitors. The synthesized compounds were also evaluated for their antiproliferative effects on the cancer cell lines (HEP-3B and A-375) to establish a proof as anticancer agents. The chemical structures of compounds were confirmed by (1)H, (13)C NMR, IR, MS and elemental analysis. The purity of compounds was also checked by HPLC analysis. Compounds with bulky groups (-OCH3, -OCF3 and -CF3) at C6-position of quinoline ring showed good activity.
作为我们对新型人类二氢乳清酸脱氢酶（hDHODH）抑制剂研究的延续，在此我们报道了新型取代喹啉-2-甲酰胺衍生物的设计、合成及药理评价。采用人类DHODH酶抑制试验来筛选合成化合物作为hDHODH抑制剂。还评估了合成化合物对癌细胞系（HEP-3B和A-375）的抗增殖作用，以证明其作为抗癌剂的效果。通过¹H、¹³C NMR、IR、MS和元素分析确定了化合物的化学结构。还通过HPLC分析检查了化合物的纯度。喹啉环C6位带有大基团（-OCH₃、-OCF₃和-CF₃）的化合物表现出良好的活性。
