New Sulfamethoxazole Derivatives as Selective Carbonic Anhydrase IX and XII Inhibitors: Design, Synthesis, Cytotoxic Activity and Molecular Modeling.

In this study new sulphamethoxazole derivatives (S1-S4, S6-S12, and S14-S22) were designed and synthesized and their structures were fully characterized and validated using NMR, mass, and IR spectroscopy, as well as elemental analyses. All new derivatives (S1-S22) were assayed against human carbonic anhydrase (hCAs IX and XII) for their inhibitory activities. hCAs IX and XII were chosen due to the fact that CAIX expression is recognized as a hypoxia marker with a poor prognosis in breast cancer. When compared to Dorzolamide HCl as a standard reference, derivatives S2, S3, S8, S9, and S15 had the most effective inhibition with low IC50 values. The active compounds were further evaluated against hCAs I and II inhibitory activity and compounds S8, S9 and S15 showed the least inhibitory effect compared to the reference standard, acetazolamide, indicating that their effect in normal cells is the lowest. Cell viability tests for the selected compounds were carried out on MCF7 (normoxia and hypoxia) and on the normal breast cell line (MCF10a) with Staurosporine as a standard. The results showed that compound S15 had a highly potent cytotoxic effect. Furthermore, cell cycle analysis results showed that compound S15 triggered cell cycle arrest and apoptosis in G1/S of MCF7 cancer cells. Finally, molecular docking was performed to point out the possible explanation for the vital structural features and key-interactions exerted by our ligands with hCAs IX and XII that might share additional designs and highlight possible leads for a hopeful anticancer agent. Consequently, sulphamethoxazole Derivative S15 could be the potential lead for emerging selective cytotoxic compounds directing h CAs IX and XII.

Hydrogel Nanocomposite-Derived Nickel Nanoparticles/Porous Carbon Frameworks as Non-Precious and Effective Electrocatalysts for Methanol Oxidation.

Innovative and facile methods for the preparation of metal nanoparticles (MNPs) with A highly uniform distribution and anchored on a unique substrate are receiving increasing interest for the development of efficient and low-cost catalysts in the field of alternative and sustainable energy technologies. In this study, we report a novel and facile metal-ions adsorption-pyrolysis method based on a hydrogel nanocomposite for the preparation of well-distributed nickel nanoparticles on 3D porous carbon frameworks (Ni@PCFs). The pyrolysis temperature effect on electrocatalytic activity toward methanol oxidation and catalyst stability was investigated. Physicochemical characterizations (SEM, TEM, and XRD) were used to determine the morphology and composition of the prepared electrocatalyst, which were then linked to their electrocatalytic activity. The experimental results indicate that the catalyst synthesized by pyrolysis at 800 °C (Ni@PCFs-8) exhibits the highest electrocatalytic activity for oxidation of methanol in alkaline media. Additionally, prepared Ni@PCFs-8 displays a remarkable increase in electrocatalytic activity after activation in 1 M KOH and excellent stability. The adsorption-pyrolysis pathway ensures that the Ni NPs are trapped in the PCFs, which can provide highly reactive surface sites. This work may provide a facile and effective strategy for preparing uniformly distributed metallic NPs on a 3D PCF substrate with high catalytic activity for energy applications.