ABSTRACT
Aim: To investigate the antileishmanial activity of novel azole compounds against Leishmania donovani, which causes deadly visceral leishmaniasis disease. Materials & methods: A focused azole-based library was screened against both promastigotes and amastigotes forms of L. donovani strains in flat-bottomed 96-well tissue culture plates and J774A.1 macrophage cell-line infected with L. donovani. The comprehensive screening of azole-based library against L. donovani strains provided novel hits, which can serve as a good starting point to initiate hit to lead optimization campaign. Results: Hits identified from azole-based library exhibited potent in vitro activity against promastigotes and amastigotes of L. donovani. Conclusion: These potent novel azole hits could be a good starting point to carry out for further medicinal chemistry exploration for antileishmania program.
Subject(s)
Azoles , Leishmania donovani , Animals , Azoles/pharmacology , Cell Line , Leishmania donovani/drug effects , Macrophages/parasitology , MiceABSTRACT
A non-diaryl quinoline scaffold 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one was identified by screening of diverse set of compounds against M. smegmatis ATP synthase. Herein, we disclose our efforts to develop the structure activity relationship against Mycobacterium tuberculosis (Mtb.H37Rv strain) around the identified hit 1. A scaffold hopping approach was used to identify compounds 14a, 14b and 24a with improved activity against MTb.H37Rv.
