title: Synthesis of 4-amino-5-cyano-2, 6-disubstituted pyrimidines as a potential antifilarial DNA topoisomerase II inhibitors.
abstract: A novel series of 4-amino-5-cyano-2, 6-disubstituted pyrimidines have been synthesized and evaluated for their in vitro antifilarial DNA topoisomerase II activity against filarial parasite Setaria Cervi. In particular compounds bearing 4-chloro-phenyl substitutent at position-6, exhibited strong inhibition at 40 microg/mL and 5 microg/mL concentration. The present study based on the biological results obtained, suggests that the nature of substitutent at position-4 in the phenyl ring directly affects DNA topoisomerase II inhibitory activity. Most of the compounds have shown better topoisomerase II inhibitory activity than the standard antifilarial drug (DEC) and the topoisomerase II inhibitors (Novobiocin, Nalidixic acid).
authors.affiliation: Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: J K
authors.initials: JK
authors.lastname: Saxena
authors.forename: Prem M S
authors.initials: PM
authors.lastname: Chauhan
mesh_terms: D000818:Animals; D004049:Diethylcarbamazine / Q000494:pharmacology; D005369:Filaricides / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009268:Nalidixic Acid / Q000494:pharmacology; D009675:Novobiocin / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D017182:Setaria Nematode / Q000187:drug effects / Q000201:enzymology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D059005:Topoisomerase II Inhibitors
chemical_list: D005369:Filaricides; D007202:Indicators and Reagents; D011743:Pyrimidines; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; D009268:Nalidixic Acid; D004049:Diethylcarbamazine