Syntheses of 2,4,6-trisubstituted pyrimidine derivatives as a new class of antifilarial topoisomerase II inhibitors.
A series of 21 compounds of trisubstituted pyrimidine derivatives have been synthesized and evaluated for their in vitro topoisomerase II inhibitory activity against filarial parasite Setaria cervi. Out of these, seven compounds (8, 11-14, 25 and 28) have shown 60-80% inhibition at 40 and 20 microg/mL concentration. Five compounds (12, 13, 14, 25 and 28) exhibited 70-80% inhibition at 10 microg/mL concentration and three compounds (13, 14 and 28) have shown 40-60% inhibition at 5 microg/mL concentration. All the above mentioned compounds have shown better topo II inhibitory activity than standard antifilarial drug (DEC) and enzyme topo II inhibitors (Novobiocin, Nalidixic acid).
Katiyar
Sanjay Babu
SB
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India.
Bansal
Iti
I
Saxena
J K
JK
Chauhan
P M S
PM
D000818:Animals; D005369:Filaricides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017182:Setaria Nematode / Q000187:drug effects*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D005369:Filaricides; D011743:Pyrimidines; D059005:Topoisomerase II Inhibitors