Structural characterization and antileishmanial activity of newly synthesized organo-bismuth(V) carboxylates: experimental and molecular docking studies.

In a quest to discover new formulations for the treatment of various parasitic diseases, a series of heteroleptic triorganobismuth(V) biscarboxylates of type [BiR 3 (O 2 CR') 2 ], where R=C 6 H 5 for 1-4 and p-CH 3 C 6 H 4 for 5-8, were synthesized, characterized and evaluated for their biological potential against L. tropica. All the synthesized complexes were fully characterized by elemental analysis, FT-IR, multinuclear ( 1 H and 13 C) NMR spectroscopy and X-ray crystallography. The crystal structures for [BiPh 3 (O 2 CC 6 H 4 (o-Br)) 2 ] (1), [BiPh 3 (O 2 CC 2 H 2 C 6 H 4 ) 2 ] (2), [BiPh 3 (O 2 CC 6 H 4 (m-NO 2 )) 2 ] (3) and [BiPh 3 (O 2 CC 6 H 4 (2-OH,3-CH 3 )) 2 ] (4) were determined and found to have a distorted pentagonal bipyramidal molecular geometry with seven coordinated bismuth center for 1-3 and for 4 distorted octahedral geometry, respectively. All the synthesized complexes demonstrated a moderate to significant activity against leishmania parasites. A broad analytical approach was followed to testify the stability for (1-8) in solid state as well as in solution and in leishmanial culture M199, ensuring them to be stable enough to exert a significant antileishmanial effect with promising results. Cytotoxicity profile suggests that tris(tolyl) derivatives show lower toxicity against isolated lymphocytes with higher antileishmanial potential. Molecular docking studies were carried out to reveal the binding modes for (1-8) targeting the active site of trypanothione reductase (TR) (PDB ID: 4APN) and Trypanothione Synthetase-Amidase structure (PDB ID 2vob).