SBA-Pr-SO3H-catalyzed synthesis of bispyrazole compounds as anti-bacterial agents and inhibitors of phosphorylated RET tyrosine kinase

摘要

Pyrazolone was prepared through the reaction of ethyl acetoacetate and hydrazine hydrate in EtOH at room temperature. Then, bispyrazole derivatives, as attractive biologically active compounds, were synthesized by reacting two equivalents of prepared pyrazolone and one equivalent of aldehyde in the presence of SBA-Pr-SO3H under solvent-free condition at 120 degrees C. The reaction time was short (3-6min), while the products' yield was high (85-97%). Discovery Studio 2.5 (Accelrys Inc, San Diego, CA, USA) was employed to dock the compounds to protein. Molecular docking (GOLD method) studies suggested that pyrazoles bind efficiently to RET kinase. Next, biological activities of the bispyrazoles were tested against some Gram-positive and Gram-negative bacteria and for antifungal activity via the disc-diffusion method. All compounds showed no significant anti-bacterial activities, but two of them showed good activities against Candida albicans.