title: Synthesis of hetero annulated isoxazolo-, pyrido- and pyrimido carbazoles: Screened for in vitro antitumor activity and structure activity relationships, a novel 2-amino-4-(3'-bromo-4'-methoxyphenyl)-8-chloro-11H-pyrimido[4,5-a]carbazole as an antitumor agent.
abstract: Claisen-Schmidt condensation of 2,3,4,9-tetrahydro-1H-carbazol-1-one with 3-bromo-4-methoxy benzaldehyde afforded the 2-(3'-bromo-4'-methoxybenzylidene)-2,3,4,9-tetrahydro-1H-carbazol-1-one 3. Compound 3 was allowed to react with different organic reactants, hydroxylamine hydrochloride, malononitrile and guanidine nitrate through condensation cum cycloaddition reactions to afford a series of the respective novel hetero annulated carbazoles such as isoxazolo-, pyrido- and pyrimido carbazoles. The structures of the compounds were established by FT-IR,1H NMR,13C NMR, X-ray diffraction and elemental analysis. The compounds have been screened for in vitro anti-tumor activity by MTT assay and displayed enviable selective growth inhibition on MCF-7 cell line compared to A-549 cell line. Apoptotic morphological changes in MCF-7 and A-549 cells were visualized using fluorescent microscopic technique. The preliminary structure activity relationships were also carried out. Data pointed out that among pyrimido carbazole compounds, 2-amino-4-(3'-bromo-4'-methoxyphenyl)-8-chloro-11H-pyrimido [4,5-a]carbazole could be exploited as an excellent therapeutic drug against cancer cell proliferation.
authors.affiliation: Department of Chemistry, Bharathiar University, Coimbatore 641046, India.
authors.forename: Karunanidhi
authors.initials: K
authors.lastname: Murali
authors.affiliation: Department of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, United Kingdom.
authors.forename: Hazel A
authors.initials: HA
authors.lastname: Sparkes
authors.affiliation: Department of Chemistry, Bharathiar University, Coimbatore 641046, India. Electronic address: prasad_125@yahoo.com.
authors.forename: Karnam Jayarampillai
authors.initials: KJ
authors.lastname: Rajendra Prasad
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry*; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011728:Pyridones / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011744:Pyrimidinones / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C000616969:2-amino-4-(3'-bromo-4'-methoxyphenyl)-8-chloro-11H-pyrimido(4,5-a)carbazole; D000970:Antineoplastic Agents; D002227:Carbazoles; D007555:Isoxazoles; D011728:Pyridones; D011743:Pyrimidines; D011744:Pyrimidinones
keywords: Cytotoxicity; Fluorescent microscopic analysis; Hetero annulated carbazoles; Pyrimidocarbazole; Structure-activity relationship