Synthesis, Characterization, In vitro and In silico Studies of a Novel Hydrazone Compound

Abstract

The geometric increase of drug-resistant bacteria pathogens has made urgent the research, development and production of new antibacterial and antifungal compounds, hence the synthesis of this novel compound as a potential antibacterial drug. As hydrazones enhanced generally with thiazoles which are 5-membered ring compound containing active nitrogen and sulphur molecules (C3H3NS) have been proven to exhibit strong antibacterial and antifungal activities, in this study, salicylaldehyde -4- thiazoleacetic acid hydrazone(SAFTAH) compound was synthesized. The novel compound was characterized and subjected to anti-microbial screening. The microbes employed were staphylococcus aureus, Escherichia Coli, streptococcus and klebsialla aerogene. The compound was found to be active against Escherichia coli as the test result recorded ++ indicating ‘very active’ unlike the other three microbes which either had + or none. To validate this inhibition of Escherichia coli by the novel compound and to detect the active site of their interactions, in silico molecular docking analysis of the novel compound against aminopeptidase N from E. coli which is known to promote virulence to the microbe in question was carried out. Six drugs commonly used for the treatment of E. coli vis-a-viz, ciprofloxacin, levofloxacin, doxycycline, rifamycin, rifaximin and sulfamethoxazole were subjected to same type of silico studies. The result of the docking indicated that the novel hydrazone compound is more efficient and effective than five of the E. coli inhibitory drugs, as the novel compound has lower binding energy of-6.6 after the docking, while ciproxafloxacin drug is -6.0, doxycycline drug, -6.2, rifamycin drug, -5.2, rifaximin drug, -5.7 and sulfamethoxazole drug, -6.6. The synthesized compound has also better interaction with the active site of the microbe concerned as shown in the images for the interactions as follows:- The newly synthesized compound has 5Hb & 9vdW = 14bonds, ciproxafloxacin has 3Hb & 9vdW = 12bonds, doxycycline has 2Hb & 4vdW = 06bonds, rifamycin has 2Hb & 4vdW = 06bonds, rifaximin has 0Hb & 4vdW = 04bonds, sulfamethoxazole has 4Hb & 6vdW = 10bonds. Compounds with lower binding energy and good interactions with the active site of the enzyme prove to be better drugs in pharmacy. Sulfamethoxazole drug which has same binding energy with the novel compound has lower interaction with the active site of the bacterium. Therefore, Salicylaldehyde -4- thiazoleacetic acid hydrazone could be a potential and better drug for the cure of E. coli infection.