Department of Chemistry, Yuvaraja's College (Autonomous), University of Mysore, Mysuru, 570005, Karnataka, India.
Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shimoga, 577203, Karnataka, India.
Biomed Pharmacother. 2019 Apr;112:108707. doi: 10.1016/j.biopha.2019.108707. Epub 2019 Feb 27.
The synthesis and antiproliferative effect of a series of quinoline and thiazole containing coumarin analogs 12a-d and 13a-f respectively, on mice leukemic cells was performed. The chemical structures of newly synthesized compounds were confirmed by IR, H NMR, C NMR and mass spectral analysis. The result indicates that, 7-methoxy-2-oxo-2H-chromene-3-carboxylic acid [4-(4-methoxy-phenyl)-thiazol-2-yl]-amide (13f) showed potent activity against EAC and DLA cells in MTT (15.3 μM), tryphan blue (15.6 μM) and LDH (14.2 μM) leak assay with 5-fluorouracil as a standard. Further, the anti-neoplastic effect of the compound 13f was verified against Ehrlich ascites tumour by BrdU incorporation, TUNEL, FACS and DNA fragmentation assays. Experimental data showed that compound 13f induces the apoptotic cell death by activating apoptotic factors such as caspase-8 &-3, CAD, Cleaved PARP, γ-H2AX and by degrading genomic DNA of cancer cells and thereby decreasing the ascitic tumour development in mice. Besides, compound 13f was also subjected for docking studies to approve the in vitro and in vivo studies. The data revealed that the compound 13f has very good interaction with caspase 3 protein by binding with amino acid Arg 207 through hydrogen bond.
对一系列喹啉和噻唑含香豆素类似物 12a-d 和 13a-f 进行了合成和抗增殖作用研究，分别在小白鼠白血病细胞上。新合成化合物的化学结构通过 IR、H NMR、C NMR 和质谱分析得到确认。结果表明，7-甲氧基-2-氧代-2H-色烯-3-羧酸[4-(4-甲氧基-苯基)-噻唑-2-基]-酰胺（13f）在 MTT（15.3 μM）、噻唑蓝（15.6 μM）和 LDH（14.2 μM）渗漏试验中对 EAC 和 DLA 细胞表现出很强的活性，以 5-氟尿嘧啶为标准。此外，通过 BrdU 掺入、TUNEL、FACS 和 DNA 片段化试验，对化合物 13f 对艾氏腹水瘤的抗肿瘤作用进行了验证。实验数据表明，化合物 13f 通过激活凋亡因子如 caspase-8 和 caspase-3、CAD、Cleaved PARP、γ-H2AX 以及降解癌细胞的基因组 DNA，诱导细胞凋亡死亡，从而减少小鼠腹水瘤的发展。此外，还对化合物 13f 进行了对接研究，以证实体外和体内研究。数据显示，该化合物 13f 通过与半胱天冬酶 3 蛋白上的氨基酸精氨酸 207 形成氢键，与 caspase 3 蛋白具有很好的相互作用。
