title: Synthesis and structure-activity relationships of novel pyrimido[1,2-b]indazoles as potential anticancer agents against A-549 cell lines.
abstract: A series of novel pyrimido[1,2-b]indazoles 5, 7 have been prepared from 3-trifluoromethyl-5-phenyl-2,6-dicyano anilines 1 via novel indazole regioisomers 3 and 4 through a facile strategy. Specific examples were evaluated for anticancer activity in vitro and found to exhibit promising activity against A-549 cell lines and are more effective than Etoposide. QSAR models were developed and validated by cross-validation method. The results of the best QSAR model were further compared with the crystal structure of tubulin protein. The binding energies estimated were found to have a good correlation with the experimental inhibitory potencies.
authors.affiliation: Fluoroorganic Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: T
authors.initials: T
authors.lastname: Yakaiah
authors.forename: B P V
authors.initials: BP
authors.lastname: Lingaiah
authors.forename: B
authors.initials: B
authors.lastname: Narsaiah
authors.forename: B
authors.initials: B
authors.lastname: Shireesha
authors.forename: B
authors.initials: B
authors.lastname: Ashok Kumar
authors.forename: S
authors.initials: S
authors.lastname: Gururaj
authors.forename: T
authors.initials: T
authors.lastname: Parthasarathy
authors.forename: B
authors.initials: B
authors.lastname: Sridhar
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor / Q000187:drug effects; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D011743:Pyrimidines; D014404:Tubulin