Synthesis and biological evaluation of oxindole linked indolyl-pyrimidine derivatives as potential cytotoxic agents. Issue 13 (1st July 2016)

• Record Type: Journal Article
• Authors: Prajapti, Santosh Kumar; Nagarsenkar, Atulya; Guggilapu, Sravanthi Devi; Gupta, Keshav Kumar; Allakonda, Lingesh; Jeengar, Manish Kumar; Naidu, V.G.M.; Babu, Bathini Nagendra
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 13(2016)
• Page Start: 3024
• Page End: 3028
• Publication Date: 2016-07-01
• Subjects: Indole -- Oxindole -- Indolyl-pyrimidine -- Cell cycle analysis -- Cytotoxicity -- Knoevenagel; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.05.019
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: In our endeavor towards the development of effective cytotoxic agents, a series of oxindole linked indolyl-pyrimidine derivatives were synthesized and characterized by IR, 1 H NMR, 13 C NMR and Mass spectral analysis. All the newly synthesized target compounds were assessed against PA-1 (ovarian), U-87MG (glioblastoma), LnCaP (prostate), and MCF-7 (Breast) cancer cell lines for their cytotoxic potential, with majority of them showing inhibitory activity at low micro-molar concentrations. Significantly, compound8e was found to be most potent amongst all the tested compounds with an IC50 value of (2.43 ± 0.29 μM) on PA-1 cells. The influence of the most active cytotoxic compound8e on the cell cycle distribution was assessed on the PA-1 cell line, exhibiting a cell cycle arrest at the G2/M phase. Moreover, acridine orange/ethidium bromide staining and annexin V binding assay confirmed that compound8e can induce cell apoptosis in PA-1 cells. These preliminary results persuade further investigation on the synthesized compounds aiming to the development of potential cytotoxic agents.