Synthesis of Novel Tetra-Substituted Pyrazole Derivatives Using Microwave Irradiation and Their Anti-Leukemic Activity Against Jurkat Cells
2025
Felipe P. Machado | Maria Clara Campos | Juliana Echevarria-Lima | Diego P. Sangi | Carlos Serpa | Otávio Augusto Chaves | Aurea Echevarria
Three previously synthesized ketene dithioacetals were used as intermediates to obtain four nucleophiles to synthesize ten tetra-substituted pyrazoles (11&ndash:20). This was achieved through microwave irradiation in ethanol as the solvent, yielding superb results ranging from 68.4% to 90.1%, in agreement with some of the principles of green chemistry. The proposed structures were determined using various spectroscopic techniques, including infrared spectroscopy and hydrogen and carbon-13 nuclear magnetic resonance. Furthermore, the compounds underwent in-silico evaluations using CLC-Pred and AdmetSAR software to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. This was combined with molecular docking calculations for four main cancer-related targets for pyrazole core, to facilitate screening for subsequent biological assessments. Based on the data generated from these analyses, it was identified two pyrazoles (11 and 18) likely to exhibit anti-tumor activity, while also demonstrating low toxicity levels. Upon selection, these two pyrazoles were subjected to toxicity assessments using the Artemia salina method and evaluated for their effects on the viability of Jurkat cancer cells with a potency of 45.05 and 14.85 µ:M to 11 and 18, respectively, and with a potency of above 100 µ:M for the non-carcinogenic cells HEK 293. Overall, the findings from these studies indicate pyrazole derivatives as potential anti-tumor candidates.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل Multidisciplinary Digital Publishing Institute