Synthesis and therapeutic evaluation of isatin-linked pyrazole motif derivatives

Abstract

Multi-target drugs possess significant therapeutic potential for the therapy of complex diseases and drug-resistant conditions. Based on this fact, isatin-pyrazole derivatives, namely, 5-substituted isatin-pyrazole derivatives 7a-d and N-alkyl isatin-pyrazole derivatives 9a-d, were prepared by merging the pyrazole motif (represented by pyrazole-3-carbohydrazide derivatives 5a, b) with the isatin moiety (represented by isatin (6a), 5-methylisatin (6b), N-methylisatin (8a), or N-ethylisatin (8b)). Spectroscopic techniques confirmed the chemical structures of 7a-d and 9a-d. These derivatives underwent in vitro therapeutic evaluations, including anti-diabetic, anti-inflammatory, and anticancer assessments. The biological evaluation revealed that the isatin-pyrazole derivative 7b exhibited anti-diabetic, anti-inflammatory, and anticancer activities. Derivative 7b exhibited activities against α-amylase (IC₅₀ = 6.41 ± 0.06 vs. 5.75 ± 0.07 (acarbose) µg/mL), α-glucosidase (IC₅₀ = 4.51 ± 0.07 vs. 4.01 ± 0.06 (acarbose) µg/mL), COX-1 (IC₅₀ = 8.75 ± 0.03 vs. 8.47 ± 0.05 (indomethacin) µg/mL), COX-2 (IC₅₀ = 8.16 ± 0.04 vs. 7.92 ± 0.04 (indomethacin) µg/mL), HepG-2 (IC₅₀ = 51.32 ± 0.51 vs. 25.80 ± 0.26 (doxorubicin) µg/mL), and MCF-7 (IC₅₀ = 73.25 ± 0.73 vs. 40.79 ± 0.41 (doxorubicin) µg/mL). Overall, derivative 7b shows promise as a multi-target candidate drug against chronic diseases.

KEY WORDS: Isatin-pyrazole derivative, Enzymatic assays, Candidate drugs, Chronic diseases, Multi-target agent

Bull. Chem. Soc. Ethiop. 2026, 40(11), 2381-2395                      

DOI: https://dx.doi.org/10.4314/bcse.v40i11.8