title: Part-1: Design, synthesis and biological evaluation of novel bromo-pyrimidine analogs as tyrosine kinase inhibitors.
abstract: A novel series of 5-bromo-pyrimidine derivatives (5a-l, 6a-h, 9a-m and 10a-d) were synthesized through multi step reactions starting from 5-bromo-2,4-dichloro pyrimidine. The newly synthesized compounds were characterized using elemental analysis and spectral data (IR, (1)H NMR, (13)C NMR and LC-MS) analysis. The titled compounds were evaluated for their in vitro cytotoxic activity against tumor cell lines panel consisted of HCT116 (human colon cancer cell line), A549 (human lung cancer cell line), K562 (human chronic myeloid leukemia cell line), U937 (human acute monocytic myeloid leukemia cell line), and L02 (human normal cell line) by using MTT assay Mosmann's method. As most of the compounds are highly potent against K562 cells, all the synthesized compounds were evaluated for Bcr/Abl tyrosine kinase inhibitory activity by using well-established ADP-Glo assay method. Dasatinib was utilized as positive control to validate in both biological evaluations. The biological activity revealed that the compounds 5c, 5e, 6g, 9e, 9f and 10c were potent Bcr/Abl kinase inhibitors among the titled compounds. Thus these compounds may be promising lead compounds to be developed as an alternative for current Dasatinib therapy.
authors.affiliation: Rallis India Limited, A TATA ENTERPRISE, # 73/1, 1C, 1D.Byregowda Industrial Layout, Srigandhanagara, Hegganahalli, Peenya, Bangalore 560091, Karnataka, India. Electronic address: chandrajan25@gmail.com.
authors.forename: Chandrashekar Suradhenupura
authors.initials: CS
authors.lastname: Munikrishnappa
authors.affiliation: East West College of Pharmacy, #63, I Phase, BEL Layout, Bharathnagar, Vishwaneedam PO, Bangalore 560091, Karnataka, India. Electronic address: sangpur@rediffmail.com.
authors.forename: Sangamesh B
authors.initials: SB
authors.lastname: Puranik
authors.affiliation: East West College of Pharmacy, #63, I Phase, BEL Layout, Bharathnagar, Vishwaneedam PO, Bangalore 560091, Karnataka, India. Electronic address: sureshkumargv@gmail.com.
authors.forename: G V Suresh
authors.initials: GV
authors.lastname: Kumar
authors.affiliation: AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530003, Andhra Pradesh, India. Electronic address: dryrp_au@rediffmail.com.
authors.forename: Y Rajendra
authors.initials: YR
authors.lastname: Prasad
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D016044:Fusion Proteins, bcr-abl
keywords: 5-Bromo-pyrimidine; Anticancer; Cytotoxicity; Dasatinib derivatives; MTT assay