Synthesis and antileishmanial activity of novel 2,4,6-trisubstituted pyrimidines and 1,3,5-triazines.
A series of 2,4,6-trisubstituted pyrimidines and 1,3,5-triazines have been synthesized and screened for their in vitro and in vivo antileishmanial activity against Leishmania donovani. Among all, 14 compounds have shown promising inhibition of 80-100% at 10 microg/ml against promastigotes and IC(50) in the range of 0.89-9.68 microg/ml against amastigotes. Three compounds 13, 32 and 33 with good selectivity index (S.I.) were screened for their in vivo activity in golden hamsters (Mesocricetus auratus) infected with MHOM/IN/80/Dd(8) strain of L. donovani and have shown moderate in vivo inhibition of 48-56% at a dose of 50 mg/kg x 5, i.p. route for 5 days.
Sunduru
Naresh
N
Division of Medicinal Chemistry, Central Drug Research Institute, MG Road, Lucknow 226001, UP, India.
Nishi
Palne
Shraddha
S
Chauhan
Prem M S
PM
Gupta
Suman
S
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D008647:Mesocricetus / Q000469:parasitology*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000981:Antiprotozoal Agents; D011743:Pyrimidines; D014227:Triazines