title: Synthesis of novel ethyl 2,4-disubstituted 8-(trifluoromethyl)pyrido[2',3':3,4]pyrazolo[1,5-a]pyrimidine-9-carboxylate derivatives as promising anticancer agents.
abstract: A series of novel pyrido[2',3':3,4] pyrazolo[1,5-a]pyrimidine derivatives 6-9 were prepared in single step starting from 3-amino-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate 5 on reaction with symmetrical and unsymmetrical aliphatic and aromatic 1,3-diketones/α,β unsaturated ketones/α,β unsaturated keto ethers under conventional method. All the final compounds 6a-c, 8a-b and 9a-l were screened for anticancer activity against five human cancer cell lines such as PC-3 (CRL-1435), MDA-MB-231 (HTB-26), Hep G2 (HB-8065), HeLa (CCL-2) and normal HUVEC (CRL-1730). Compounds 8a, 9f and 9k which showed promising anticancer activity have been identified. Further, the promising compounds (8a and 9f) were able to inhibit the human topoisomerase I (TopI) activity similar to that of camptothecin.
authors.affiliation: Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: N
authors.initials: N
authors.lastname: Ravi Kumar
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: Y
authors.initials: Y
authors.lastname: Poornachandra
authors.affiliation: Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: D
authors.initials: D
authors.lastname: Krishna Swaroop
authors.affiliation: Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: G
authors.initials: G
authors.lastname: Jitender Dev
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: C
authors.initials: C
authors.lastname: Ganesh Kumar
authors.affiliation: Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India. Electronic address: narsaiah@iict.res.in.
authors.forename: B
authors.initials: B
authors.lastname: Narsaiah
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles
keywords: 1,3 diketones; Anticancer activity; Pyrazolo[3,4-b]pyridine; Pyrimidine; α,β unsaturated ketones