In this work, we decided to synthesize an expanded series of Sterioselective indole oxime ethers and Biaryl bifunctional ethers of prototype-I-II and investigated their biological effects against the Leishmania parasites. The newly synthesized compounds exhibited interesting biological activity. This work involves design and synthesis of novel azoles with aryloxy and oximino functions making use of our developed methodology of the water mediated Mannichaldol-type adducts. The preliminary investigations of biological results revealed that, these compounds have potential as antileishmanial agents and has opened a new avenue for further exploration.