Design, Synthesis, and Pharmacological Evaluation of Novel Isatin Scaffolds as Potent Anti-Inflammatory and Antibacterial Agents

Abstract

In this study, novel Mannich bases were synthesized from Schiff bases of isatin using various secondary amines. The compounds were structurally characterized using FTIR, ¹H NMR, ¹3C NMR, mass spectrometry, and elemental analysis. Their anti-inflammatory potential was evaluated both in vitro and in vivo, with compounds IS-SM1, IS-SM5, and IS-S1 showing significant activity (IC₅₀ values: 29.84, 34.64, and 31.89 µg/mL) comparable to the standard (IC₅₀: 29.17 µg/mL). Molecular docking studies using AutoDock Vina revealed strong binding affinities (scores ranging from −7.4 to −8.9) against cyclooxygenase-1, further supported by interaction analysis using Discovery Studio 2021. Additionally, IS-S1, IS-SM1, IS-SM4, and IS-SM5 demonstrated notable antibacterial activity, with inhibition zones ranging from 24.43 to 26.93 mm against Gram-positive and 17.11 to 22.53 mm against Gram-negative bacteria. These findings confirm the dual anti-inflammatory and antibacterial potential of the synthesized compounds. The current reaction scheme holds promise for further structural modifications—such as acetylation, cyclization, and chalcone formation—to explore additional pharmacological activities like anticancer, antitubercular, and antidiabetic effects, thus opening new avenues in medicinal chemistry research.