One-Pot Synthesis and in Silico Molecular Docking Studies of Arylselanyl Hydrazides as Potential Antituberculosis Agents

Abstract

The present study reports a simple two-step method for the synthesis of arylselanyl hydrazide derivatives using hypophosphorous acid and polyethylene glycol (H₃ PO₂ /PEG-400) as an alternative reducing system and hydrazine hydrate (NH₂ NH₂ ⋅xH₂ O/50-60 %). This single-vessel procedure was employed with methyl acrylate 2a and methyl bromoacetate 2b using diaryl diselenides to generate the nucleophile species to produce, respectively, 3-(arylselanyl)propane-hydrazides 4a-e and 2-(arylselanyl)acetohydrazides 5a-e with good yields by accelerating the reduction of -Se-Se- bond, when compared to available methods. The synthesized molecules are structurally similar to the isoniazid (INH). Therefore, we perform in silico molecular docking studies, using the lactoperoxidase enzyme, in order to verify whether the INH Se derivatives could interact in a similar way to INH at the active site of the mammalian enzyme. The in silico results indicated a similar type of interaction of the arylselanyl hydrazide derivatives with that of INH. In view of the similar in silico interaction of the selenium derivatives of INH, the arylselanyl hydrazide derivatives reported here should be tested against Mycobacterium tuberculosis in vitro.

Keywords: H3PO2; arylselanyl hydrazides; hydrazides; molecular docking.