Amujuri Devi, Siva Bandi, Poornima B, Sirisha Katukuri, Sarma A V S, Lakshma Nayak V, Tiwari Ashok K, Purushotham U, Suresh Babu K
Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India.
Centre for NMR & Structural Chemistry, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500607, India.
Eur J Med Chem. 2018 Apr 10;149:182-192. doi: 10.1016/j.ejmech.2018.02.066. Epub 2018 Feb 24.
A new series of Schizandrin (1) derivatives were synthesized utilizing the C-9 position of the Schizandrin core and evaluated for their cytotoxic activities against HeLa (cervical cancer), A549 (lung cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines. Among the synthesized series, 4e, 4f, 4g and 5 showed potent activities against tested cell lines. More significantly, compound 5 exhibited most potent cytotoxic activity against DU-145 with an IC value of 1.38 μM which is comparable to the standard agent, doxorubicin. Further, flow cytometry analysis indicated that 5 arrested cells in G2/M phase and consequently leading to apoptosis. Molecular docking analysis showed that 5 occupied the colchicine binding pocket of tubulin. Overall, the present study demonstrates that 5, as a mitotic-agent.
利用五味子醇核心的C-9位合成了一系列新的五味子醇（1）衍生物，并评估了它们对HeLa（宫颈癌）、A549（肺癌）、MCF-7（乳腺癌）和DU-145（前列腺癌）细胞系的细胞毒性活性。在合成的系列中，4e、4f、4g和5对测试的细胞系显示出强效活性。更显著的是，化合物5对DU-145表现出最有效的细胞毒性活性，IC值为μM，与标准药物阿霉素相当。此外，流式细胞术分析表明，5使细胞停滞在G2/M期并因此导致细胞凋亡。分子对接分析表明，5占据了微管蛋白的秋水仙碱结合口袋。总体而言，本研究表明，5作为一种有丝分裂剂。
