Publication Type : Journal Article
Publisher : European Journal of Medicinal Chemistry
Source : European Journal of Medicinal Chemistry, Volume 104, p.11-24 (2015)
Url : https://www.sciencedirect.com/science/article/pii/S0223523415302695
Keywords : 3-Hydroxy-oxindole, Anticancer, apoptosis, Azide-nitrile cycloaddition, Isatin epoxide, Tetrazoles
Campus : Kochi
School : School of Pharmacy
Department : Pharmacology
Year : 2015
Abstract : A simple method for isatin spiro-epoxide ring-opening by sodium cyanide in water to obtain a variety of isatin hydroxy nitriles has been developed. Further, these intermediates have been converted into new 3-tetrazolylmethyl-3-hydroxy-oxindole hybrids via azide-nitrile cycloaddition reaction in a sealed tube. These compounds were evaluated for their in vitro anticancer activity on five human cancer cell lines i.e. breast (BT549 and MDA MB-231), prostate (PC-3 and DU-145) and ovarian (PA-1). The compounds 6d and 6r showed potent anticancer activity against DU-145 cell line with IC50 values in the range of 7.01 ± 0.91 and 4.26 ± 0.09 μM respectively. The compounds 6d, 6g, 6q and 6r were also tested on human normal prostate epithelial (RWPE-1) cells and found to be safer with lesser cytotoxicity. The morphology and long term clonogenic survival of DU-145 cells were severely affected by compound 6r. Cell cycle analysis revealed that the compounds arrest the cells in G2/M phase. Acridine orange/ethidium bromide (AO/EB) staining, DAPI staining, annexin-V binding assay and DNA fragmentation analysis showed that cell proliferation was inhibited through induction of apoptosis. Moreover, one of the compounds 6r treatment led to collapse of the mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) in DU-145 cells
Cite this Research Publication : P. Sharma, Senwar, K. Ram, Dr. Manish Kumar Jeengar, T. Reddy, S., V.G.M. Naidu, Kamal, A., and Shankaraiah, N., “H2O-mediated isatin spiro-epoxide ring opening with NaCN: Synthesis of novel 3-tetrazolylmethyl-3-hydroxy-oxindole hybrids and their anticancer evaluation”, European Journal of Medicinal Chemistry, vol. 104, pp. 11-24, 2015.