Visible Light‐Promoted Catalyst‐Free (VLCF) Scalable Synthesis of Novel Derivatives of Isoniazid and Maleimide

Abstract We have developed a Visible Light Promoted Catalyst‐Free (VLCF) approach to synthesize novel conjugates of Isoniazid and Maleimide. This method involves the formation of an electron donor‐acceptor (EDA) complex between isoniazid and maleimide the photochemical activity of this complex drives the transformation. We successfully synthesized Isoniazid‐Maleimide derivatives (3a–d) at gram scale under visible light irradiation without an additional photo catalyst and without chromatographic purification resulting in excellent yields in a recyclable green solvent. Molecular docking was employed to predict the in silico anti‐tubercular activity and binding modes at the active site of enoyl‐ACP reductase, InhA. The newly synthesized compounds (3a–d) exhibited high binding affinity compared to Isoniazid and Isoniazid‐NAD adduct, indicating their potential for more effective anti‐tubercular activity. ADME analysis revealed favourable physicochemical properties, lipophilicity, water solubility, pharmacokinetics, and drug‐likeness for compound 3a, positioning it as a promising candidate for further drug discovery and development.