title: Synthesis and biological evaluation of oxindole linked indolyl-pyrimidine derivatives as potential cytotoxic agents.
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.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Prajapti
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Atulya
authors.initials: A
authors.lastname: Nagarsenkar
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Sravanthi Devi
authors.initials: SD
authors.lastname: Guggilapu
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Keshav Kumar
authors.initials: KK
authors.lastname: Gupta
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Lingesh
authors.initials: L
authors.lastname: Allakonda
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Manish Kumar
authors.initials: MK
authors.lastname: Jeengar
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: V G M
authors.initials: VGM
authors.lastname: Naidu
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: bathini.niperhyd@gov.in.
authors.forename: Bathini Nagendra
authors.initials: BN
authors.lastname: Babu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D066244:Proton Magnetic Resonance Spectroscopy; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011743:Pyrimidines
keywords: Cell cycle analysis; Cytotoxicity; Indole; Indolyl-pyrimidine; Knoevenagel; Oxindole