title: Discovery of triazine mimetics as potent antileishmanial agents.
abstract: The World Health Organization has classified the leishmaniasis as a major tropical disease. The discovery of new compounds for leishmaniasis is therefore a pressing concern for the anti-infective research program. We have synthesized 19 compounds of triazine dimers as novel antileishmanial agents. Most of the synthesized derivatives exhibited better activity against intracellular amastigotes (IC50 ranging from 0.77 to 10.32 μM) than the control, pentamidine (IC50 = 13.68 μM), and are not toxic to Vero cells. Compounds 14 and 15 showed significant in vivo inhibition of 74.41% and 62.64%, respectively, in L. donovani/hamster model. Moreover, expansion of Th1-type and suppression of Th2-type immune responses proved that compound 14 stimulates mouse macrophages to prevent the progression of leishmania parasite. The molecular docking studies involving PTR1 protein PDB further validated the concepts involved in the design of these compounds. Among the investigated analogues, compound 14 has emerged as the potential one to enlarge the scope of the study.
authors.affiliation: Medicinal and Process Chemistry Division and Division of Parasitology, CSIR-Central Drug Research Institute , Lucknow 226031, U.P., India.
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Chauhan
authors.affiliation: Medicinal and Process Chemistry Division and Division of Parasitology, CSIR-Central Drug Research Institute , Lucknow 226031, U.P., India.
authors.forename: Moni
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Medicinal and Process Chemistry Division and Division of Parasitology, CSIR-Central Drug Research Institute , Lucknow 226031, U.P., India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Shivahare
authors.affiliation: Medicinal and Process Chemistry Division and Division of Parasitology, CSIR-Central Drug Research Institute , Lucknow 226031, U.P., India.
authors.forename: Utsab
authors.initials: U
authors.lastname: Debnath
authors.affiliation: Medicinal and Process Chemistry Division and Division of Parasitology, CSIR-Central Drug Research Institute , Lucknow 226031, U.P., India.
authors.forename: Suman
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Medicinal and Process Chemistry Division and Division of Parasitology, CSIR-Central Drug Research Institute , Lucknow 226031, U.P., India.
authors.forename: Yenamandra S
authors.initials: YS
authors.lastname: Prabhakar
authors.affiliation: Medicinal and Process Chemistry Division and Division of Parasitology, CSIR-Central Drug Research Institute , Lucknow 226031, U.P., India.
authors.forename: Prem M S
authors.initials: PM
authors.lastname: Chauhan
keywords: L. donovani; in vitro/in vivo; pentamidine; pteridine reductase 1; triazine