Shareef Mohd Adil, Duscharla Divya, Ramasatyaveni G, Dhoke Neha R, Das Amitava, Ummanni Ramesh, Srivastava Ajay Kumar
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad 500 007, India.
Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad 500 007, India.
Eur J Med Chem. 2015 Jan 7;89:128-37. doi: 10.1016/j.ejmech.2014.10.050. Epub 2014 Oct 18.
A series of fifteen podophyllotoxin derived esters have been synthesized and their anti-cancer properties have been evaluated against A549 (lung cancer), DU-145 (prostate cancer), HepG2 (liver cancer), HeLa (cervical cancer) and MCF-7 (breast cancer) cell lines. Five compounds of the series 8a, 8g-h, 8m and 8o showed IC50 values in the range of 0.71-10.94 μM. Among compounds, 8g and 8h showed significant cytotoxicity towards all the types of cancer studied. Cell cycle analysis revealed that the compounds 8a, 8m and 8o inhibit proliferation by cell cycle arrest. Also Hoechst-positive nucleus indicating apoptosis of these cells was observed in presence of 8g-h. Further studies revealed that these compounds inhibit tubulin polymerization and leads to the inactivation of AKT/PKB that are known to play an important role in the proliferation of cancer cells.
已合成了一系列十五种鬼臼毒素衍生酯，并针对A549（肺癌）、DU - 145（前列腺癌）、HepG2（肝癌）、HeLa（宫颈癌）和MCF - 7（乳腺癌）细胞系评估了它们的抗癌特性。该系列中的五种化合物8a、8g - h、8m和8o的半数抑制浓度（IC50）值在0.71 - 10.94μM范围内。在这些化合物中，8g和8h对所有研究类型的癌症均表现出显著的细胞毒性。细胞周期分析表明，化合物8a、8m和8o通过细胞周期阻滞抑制增殖。此外，在8g - h存在的情况下观察到Hoechst阳性细胞核，表明这些细胞发生凋亡。进一步研究表明，这些化合物抑制微管蛋白聚合，并导致已知在癌细胞增殖中起重要作用的AKT/PKB失活。
