Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer’s, Anti-Inflammatory, and Cytotoxic Agents: In Vitro Studies with Computational Predictions

In this innovative research, we aim to reveal pyrazole-based Schiff bases as new multi-target agents. In this context, we re-synthesized three sets of pyrazole-based Schiff bases, 5a–f, 6a–f, and 7a–f, to evaluate their biological applications. The data from in vitro biological assays (including antioxidant and scavenging activities, anti-diabetes, anti-Alzheimer’s, and anti-inflammatory properties) of the pyrazole-based Schiff bases 5a–f, 6a–f, and 7a–f showed that the six pyrazole-based Schiff bases 5a, 5d, 5e, 5f, 7a, and 7f possess the highest biological properties among the compounds evaluated. The cytotoxicity against lung (A549) and colon (Caco-2) human cancer types, as well as normal lung (WI-38) cell lines, was evaluated. The data from the cytotoxicity investigation demonstrated that the three Schiff bases 5d, 5e, and 7a are active against lung (A549) cells, while the two Schiff bases 5e and 7a exhibited the highest cytotoxicity towards colon (Caco-2) cells. Additionally, the enzymatic activities against caspase-3 and Bcl-2 of the six pyrazole-based Schiff bases 5a, 5d, 5e, 5f, 7a, and 7f were evaluated. Furthermore, we assessed the in silico absorption, distribution, metabolism, and toxicity (ADMT) properties of the more potent pyrazole-based Schiff bases. After modifying the structures of the six pyrazole-based Schiff bases, we plan to further extend the studies in the future.