title: Synthesis and anticancer activity of oxindole derived imidazo[1,5-a]pyrazines.
abstract: A series of oxindole derivatives of imidazo[1,5-a]pyrazines were prepared and confirmed by 1H NMR, mass and HRMS data. These compounds were evaluated for their anticancer activity against a panel of 52 human tumor cell lines derived from nine different cancer types: leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate and breast. Among them compound 7l showed significant anticancer activity with GI50 values ranging from 1.54 to 13.0 μM. Cell cycle arrest was observed in G0/G1 phase upon treatment of A549 cells with 6.5 μM (IC50) concentration of compound 7l and induced apoptosis. This was confirmed by Annexin V-FITC as well as DNA fragmentation analysis and interestingly this compound (7l) did not affect the normal cells.
authors.affiliation: Division of Organic Chemistry, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India. ahmedkamal@iict.res.in
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
authors.forename: G
authors.initials: G
authors.lastname: Ramakrishna
authors.forename: P
authors.initials: P
authors.lastname: Raju
authors.forename: A V Subba
authors.initials: AV
authors.lastname: Rao
authors.forename: A
authors.initials: A
authors.lastname: Viswanath
authors.forename: V Lakshma
authors.initials: VL
authors.lastname: Nayak
authors.forename: Sistla
authors.initials: S
authors.lastname: Ramakrishna
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D000078183:Oxindoles; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007211:Indoles; D000078183:Oxindoles; D011719:Pyrazines; C517813:imidazo(1,5-a)pyrazine; C022960:2-oxindole