Reduction of Bacterial Folic Acid Production and Cell Membrane Disruption of Klebsiella pneumoniae by Two Amino Substituted Pyridyl Compounds: An Experimental and In Silico Approach

As bacterial resistance increases, more effective antibiotics are needed, necessitating drug discovery research. Therefore, in this paper we discuss the potential modes of action of two organic compounds, 4-(pyridin-4-ylmethoxy)aniline (L2) and pyridin-4-ylmethyl 4-aminobenzoate (L1) as antibacterial agents against Klebsiella pneumoniae, which were both studied in vitro. The folic acid production assay showed that the compound L1 was more effective than L2 and silver sulfadiazine AgSD (control) at inhibiting folic acid production. The compounds had better binding scores than the DHPS binding substrate para-amino benzoic acid (PABA), according to the molecular docking studies, and L1 was able to bind to the PABA binding pocket, demonstrating competitive antagonism. Moreover, the molecular docking data for AgSD and L1 were found to be in good agreement with the corresponding experimental results. On the other hand, AgSD was better in affecting the integrity of the bacterial membrane as this is its primary mode of action. L2 and L1 showed a significant amount of AKP release than the vehicle control, suggesting that this may also be a potential mode of action of compounds with their pharmacophores. The binding energies of these compounds corroborated with the AKP release data, these were − 5.70, − 5.52 and − 5.27 kcal/mol for AgSD, L1 and L2 respectively, showing that AgSD was the best followed by L1 and L2.