Synthesis, biological evaluation and in silico studies of 1,2,3-triazolyl-metronidazole derivatives against Leishmania major

Abstract

A simple and effective approach for the preparation of 1,2,3-triazolyl-based metronidazole hybrid analogues as promising anti-Leishmania agents using [CuL-SiO-HA] as a catalyst is described. The catalyst was fully characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission, thermogravimetric analysis (TGA), energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), and inductively coupled plasma (ICP) analysis. Exploiting this non-toxic and mild catalyst provides good to excellent yields of final products with reactive pharmacophores. All compounds were assessed against Leishmania major, and it was determined that 16k and 16j were the most potent compounds with IC₅₀ values of 7.5 μM and 8.1 μM compared to metronidazole as a reference drug, respectively. Furthermore, molecular docking studies were carried out to determine the detailed binding modes and critical interactions with the target protein. The drug likeness and in silico ADMET for all compounds were predicted. The computational results illustrated desirable matches with anti-Leishmania activity, and in this regard, 16k and 16j can be considered as future drug candidates against Leishmania.