Synthesis of Novel Mannich Bases of Indole and N-phenylaniline with its Molecular Docking, In silico Absorption, Distribution, Metabolism, and Excretion Profiling, In vitro Anti Tubercular Activity and Cytotoxicity Studies

A BSTRACT Background: The bacillus Mycobacterium tuberculosis (MTB) is the major reason of the most infectious disease tuberculosis (TB). Regarding the past, it has ranked higher than human immunodeficiency virus/AIDS as the greatest source of death from a sole contagious disease for the past 5 years. The mannich reaction is a condensation of three molecules containing active hydrogen, an aldehyde, a primary or secondary amine, and one acidic hydrogen atom. Objective: This study illustrates the in silico physicochemical analysis, drug likeliness and toxicity prediction, synthesis, characterization using Fourier transform infrared spectroscopy, mass spectrum, and 1 H nuclear magnetic resonance techniques, and antitubercular activity of some new mannich bases of indole and N-phenylaniline (MB1-MB24). Materials and Methods: Molecular docking against target proteins (PDB ID: 5OEQ) is evaluated using AutoDock Vina 1.5.6. Potentially hit compounds were identified early on by virtue of the development of modern techniques such as absorption, distribution, metabolism, and excretion, and the potential pharmacokinetic and pharmacodynamic advantages and disadvantages of these prospective treatment prospects were predicted. The in vitro antitubercular activity of MB9, MB18, and MB24 derivatives against MTB ( Mla H37Rv) was tested. Results: All designed compounds follow Lipinski’s rule of five. The target molecule with the highest binding energy was MB24. From the in silico study designed, derivatives were suggested to be good antitubercular agents through Mycothiol S-conjugate amidase inhibitors. Compound MB24 has more powerful antitubercular action against the tested strain of MTB ( Mla H37Rv) bacteria when tested in vitro . Conclusion: Using the MB24, MB9, and MB18 compounds, pharmacological research is expected with the goal of discovering new, intriguing, physiologically active molecules.