In silico studies and antimicrobial investigation of synthesised novel N-acylhydrazone derivatives of indole

Indole is an exceptional scaffold in the discovery and design of drugs with different mechanisms and biological activity. Numerous research has been conducted on N-acylhydrazones of indole and its derivatives, however, no account of the synthesis, molecular docking and the antimicrobial activities of the eleven synthesised compounds has never been reported. The study was therefore designed to synthesize, characterize, carry out molecular docking and determine the antimicrobial activities of novel N-acylhydrazone derivatives of indole. Aldol condensation of synthesised hydrazides with aromatic aldehydes led to the formation of the N-acylhydrazone derivatives of indole. The structure of the compounds were confirmed by proton nuclear magnetic Resonance ( 1 H NMR) and electron impact mass spectrometry (EIMS). The N-acylhydrazones were screened against ten microbes (four fungi three Gram-positive bacteria, and three Gram-negative bacteria) at concentrations of 100 to 6.26 mg/mL, using agar well diffusion and fungi carpeted antimicrobial assays. Gentamicin (5 mg/mL) was the positive control for bacteria while tioconazole (70%) was used for fungi. The molecular docking studies was done and the docking scores recorded accordingly on four antimicrobial receptors with PDB codes (3CR7, 3FHV, 6L1L and 6SPC). The synthesised compounds displayed moderate activity against the test organisms with the zone of inhibitions range 24 ± 0.00 to 18 ± 0.70 mm at 100 mg/mL as compared to the standards (gentamicin 10 µg/mL (36 ± 1.41), tioconazole 70% (26 ± 4.24)). All synthesised N-acylhydrazone derivatives exhibited a good number of hydrophobic interactions, classical and non-classical hydrogen bonding with the docked protein enzymes. Compound 10 and 1 were predicted to exhibit highest binding energy of -9.7 and -9.2 kcal/mole respectively with the binding site of 6SPC. Other compounds were found to have higher predicted binding energies than the standard drugs. Previously, there has been no report on the synthesis of N-acylhydrazone derivatives of Indole used in this study, their molecular docking and antimicrobial analyses is being reported for the first time. Since microbial resistance poses a major threat to human health globally, this research screened the synthesised compounds on fungi and bacteria and were found to be active against the selected microbes. These compounds if ameliorated, will reduce the uncontrollable rise in the multidrug-resistant (MDR) bacteria in Africa and in the universe. Therefore, since the synthesised N-acylhydrazone derivatives have potential in inhibiting microbial growth and showed good binding parameters with the tested enzymes, they could be effectively developed into antimicrobial agents useful for treating a wide range of microbial infections. Further research should conducted on the drugability, toxicity, minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the drug compounds.