2. Academic Validation
  3. Synthesis and biological evaluation of oxindole linked indolyl-pyrimidine derivatives as potential cytotoxic agents

Synthesis and biological evaluation of oxindole linked indolyl-pyrimidine derivatives as potential cytotoxic agents

  • Bioorg Med Chem Lett. 2016 Jul 1;26(13):3024-3028. doi: 10.1016/j.bmcl.2016.05.019.
Santosh Kumar Prajapti 1,  Atulya Nagarsenkar 1,  Sravanthi Devi Guggilapu 1,  Keshav Kumar Gupta 1,  Lingesh Allakonda 2,  Manish Kumar Jeengar 2,  V G M Naidu 2,  Bathini Nagendra Babu 3
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 2 Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 3 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: bathini.niperhyd@gov.in.
PMID: 27210438 DOI: 10.1016/j.bmcl.2016.05.019
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, compound 8e was found to be most potent amongst all the tested compounds with an IC50 value of (2.43±0.29μM) on PA-1 cells. The influence of the most active cytotoxic compound 8e 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 compound 8e 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.

Keywords

Cell cycle analysis; Cytotoxicity; Indole; Indolyl-pyrimidine; Knoevenagel; Oxindole.

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