Oxabicyclo derivatives as novel antileishmanial compounds.

摘要

The present invention relates to biomedical field and particularly relates to novel compounds for the treatment of diseases caused by parasites of the Leishmania genus, for example Leishmaniasis. In a further aspect, derivatives of Oxabicyclo compounds having significant antileishmanial activity, both on promastigote and amastigote stages tested in-vitro and in-vivo for their activity against Leishmania parasite. It specifically relates to the preparation process of novel Oxabicyclo compounds and designing the assay for effective treatment of Leishmaniasis. It discloses small molecules, oxabicyclo[3.3.1]nonanones as inhibitors of key redox enzymes, trypanothione synthetase (TryS) and trypanothione reductase (TryR) of Leishmania parasites. These new class of compounds i.e. oxabicyclo[3.3.1]-nonanones as antileishmanial agents. The antileishmanial activity of these compounds is mediated through inhibition of two important redox enzymes of the parasite TryS and TryR which are necessary for the parasite survival. The inhibition of these enzymes further causes ROS accumulation in the cell causing oxidative stress that elicited apoptotic cascade in parasite. Although these compounds show modest IC50 and Ki values against the parasite and the target enzymes, respectively, they identify a chemical space to design and develop inhibitors based on these compounds for better antileishmanial agents. The antileishmanial activity in both in vitro and in vivo showed prominent effect with no significant toxicity.