Search

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 mM and 8.1 mM 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. [ABSTRACT FROM AUTHOR]

• A set of 1,2,3-triazolyl-based metronidazole hybrids (7a-m) was synthesized from the reaction of 2-methyl-5-nitro-1-(prop‑2-yn-1-yl)−1H-imidazole with β-azido alcohols in the presence of [CuL] as catalyst. • The in vitro cytotoxic activity of the synthesized compounds 7a-m were investigated against human melanoma cell line A375, using MTT assay. • Among all the synthesized compounds, compound 7l was found to be the most potent derivative with IC 50 value of 62.5 µM. • The molecular docking studies and molecular dynamic simulation were carried out to obtain the binding mode of these derivatives in the binding site of receptor. • This work is helpful for researchers who planning to design and develop anticancer agents. In the current study, a set of 1,2,3-triazolyl-based metronidazole hybrids (7a-m) was synthesized from the reaction of 2-methyl-5-nitro-1-(prop‑2-yn-1-yl)-1H-imidazole with β-azido alcohols in the presence of [CuL] as catalyst. The chemical structures of the synthesized compounds were characterized using different spectroscopic techniques (IR, 1H NMR, 13C NMR, Mass) and elemental analysis. Then, the in vitro cytotoxic activity of the synthesized compounds 7a-m were investigated against human melanoma cell line A375, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytotoxic results showed that these compounds have moderate anticancer activity compared to methotrexate as a reference drug. Among all the synthesized compounds, compound 7l was found to be the most potent derivative with IC 50 value of 62.5 µM. Finally, the molecular docking studies and molecular dynamic simulation were carried out to obtain the binding mode of these derivatives in the binding site of receptor. The results of docking studies were in good agreement with the in vitro cytotoxic results. [Display omitted] [ABSTRACT FROM AUTHOR]