Synthesis, Characterization, In Silico ADME Profiling, MD Simulations and Unveiling Antibacterial Activities of Novel (E)-5-Amino-3-Styryl-1H-Pyrazole-4-Carbonitrile Derivatives: A Tandem Michael Addition Approach

An easy and environment benign, time-efficient Tandem Michael addition for the synthesis of (E)-5-amino-3-styryl-1H-pyrazole-4-carbonitrile derivatives using the components of Cinnamaldehyde, hydrazine, and malononitrile through MCR approach have been developed. Using AlCl3 as a catalyst in aqueous ethanol (1:1) medium, it yields 79–89% of the pyrazole derivative within the period of 30 minutes. The synthesised compounds were investigated for MM2 to predict the molecular behaviour and energy calculation by Chem 3D software, ADME (Adsorption, Distribution, Metabolism and Excretion) properties using Swiss ADME software to profile pharmacokinetic properties of potential drugs, and the compounds' molecular docking (MD) simulations procedure was done with the proteins 4O9I and 2HI9 Hydrolase inhibitors. The protein-ligand interactions between the synthesised compound and the chosen protein revealed antibacterial activity against gram positive and gram negative bacterium, with improved results shows the role of hydrolase inhibitors and their relevance in biological activity. These intriguing findings indicate that the synthesized compounds might be suitable candidates for the development of novel antibacterial drugs in drug discovery.