One Pot Synthesis, Crystal Structure, Hirshfeld Studies, Docking Simulation and Antimicrobial Efficacy Assay of New Fused/Substituted Pyrazolinyl–Thiazolidinyl–Indolone Triheterocyclic Hybrid Scaffolds

In this present investigation, a new series of functionalized hybrid compounds containing three bioactive triheterocyclic templates, pyrazolines, thiazolidinones, and indolones are designed and synthesized via multicomponent, one-pot reaction of 3-(4-chlorophenyl)-5-[4-(propan-2-yl)phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide with various substituted isatin derivatives and chloroacetic acid in the presence of fused sodium acetate and glacial acetic acid viz ring closure mechanism followed by dehydration. The formation of new scaffolds 4–7(a–c) is evidenced by analytical and spectral studies. The single-crystal X-ray diffraction study supported the molecular structure of compound 4a as a triclinic crystal system with a P$\overline{1}$ space group and Z = 2. Interestingly, the compound is crystallized with two molecules (A/B) and one water molecule in the asymmetric unit, and the crystal packing is stabilized by intra and intermolecular hydrogen bonds. To quantify the percentage of intermolecular contacts and electrostatic potential distribution in crystal packing, Hirshfeld surface analysis was performed. All the compounds were screened for their preliminary antimicrobial activity against a panel of bacterial and fungal strains. The newly synthesized compounds exhibited fairly encouraging in vitro antibacterial activity, so the validation of the potent compound was done by docking against the antibacterial target Escherichia coli FabH (PDB: 5BNS). The virtual screening is focused on ADME and drug-likeliness properties to identify their putative ligand-protein interactions using Schrödinger software.