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

Abstract

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, <b>5a</b>-<b>f</b>, <b>6a</b>-<b>f</b>, and <b>7a</b>-<b>f</b>, to evaluate their biological applications. The data from <i>in vitro</i> biological assays (including antioxidant and scavenging activities, anti-diabetes, anti-Alzheimer's, and anti-inflammatory properties) of the pyrazole-based Schiff bases <b>5a</b>-<b>f</b>, <b>6a</b>-<b>f</b>, and <b>7a</b>-<b>f</b> showed that the six pyrazole-based Schiff bases <b>5a</b>, <b>5d</b>, <b>5e</b>, <b>5f</b>, <b>7a</b>, and <b>7f</b> 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 <b>5d</b>, <b>5e</b>, and <b>7a</b> are active against lung (A549) cells, while the two Schiff bases <b>5e</b> and <b>7a</b> 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 <b>5a</b>, <b>5d</b>, <b>5e</b>, <b>5f</b>, <b>7a</b>, and <b>7f</b> were evaluated. Furthermore, we assessed the <i>in silico</i> 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.