Bio-Organic and Photochemistry Laboratory, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143 005, Punjab, India.
Department of Botanical and Environment Sciences, Guru Nanak Dev University, Amritsar 143 005, Punjab, India.
Eur J Med Chem. 2014 Nov 24;87:228-36. doi: 10.1016/j.ejmech.2014.09.049. Epub 2014 Sep 16.
A series of endoperoxides (3a-j) were synthesized and evaluated for cytotoxic activity against four human cancer cell lines by using SRB dye assay. All the compounds displayed moderate to high cytotoxic effect against almost all investigational cancer cells. Particularly, compounds bearing electron withdrawing groups such as nitro substituted compound 3j (IC50 = 0.001 μM) and fluoro substituted compound 3i (IC50 = 0.003 μM) showed comparatively more cytotoxic potential than standard drugs against lung cancer cell line (A549). All synthesized endoperoxides (3a-j) were further evaluated for their apoptotic potential through various parameters such as flow-cytometric analysis of nuclear DNA, flow-cytometric determination of mitochondrial membrane potential (ΔΨm), spectrofluorimetric estimation of intracellular ROS level and caspase-3 & 9 assays in treated lung cancer cells (A549); results reveal that endoperoxides induce apoptosis in cancer cells via mitochondrial pathway.
我们合成了一系列的内过氧化物（3a-j），并用 SRB 染料法评估了它们对四种人癌细胞系的细胞毒性。所有化合物对几乎所有的受试癌细胞均表现出中等至较强的细胞毒性作用。特别是含有吸电子基团的化合物，如硝基取代的化合物 3j（IC50 = 0.001 μM）和氟取代的化合物 3i（IC50 = 0.003 μM），对肺癌细胞系（A549）的细胞毒性比标准药物更强。我们还通过各种参数进一步评估了所有合成的内过氧化物（3a-j）的凋亡潜力，如细胞核 DNA 的流式细胞术分析、线粒体膜电位（ΔΨm）的流式细胞术测定、细胞内 ROS 水平的荧光光度法估计以及 caspase-3 和 caspase-9 测定在处理后的肺癌细胞（A549）中；结果表明，内过氧化物通过线粒体途径诱导癌细胞凋亡。
