Indeno[1,2‐b]pyridin‐5‐one derivatives containing azo groups and their hydrazonal precursors: Synthesis, antimicrobial profile,DNAgyrase binding affinity, and molecular docking

Abstract

AbstractThe prevalence of germs that are resistant to many antibiotics is rising rapidly the world over. There is a large group of researchers actively looking for better medicines. Here, we designed two series of hydrazonal and indeno[1,2‐b]pyridin‐5‐one bearing hydrazone and azo‐groups to test their antimicrobial activity. Molecular structures of all derivatives were assured based on their spectral data and elemental analyses. Results of the antimicrobial activity of the tested hydrazone and azo compounds showed promising potential for several derivatives. The minimum inhibitory concentrations (MICs) of hydrazones4a‐hand6a‐gdisplayed good antibacterial reactivities with a range of 3.91–250 μg/mL and moderate antifungal activity with a range of 15.6–500 μg/mL. The most promising hydrazone4fand azo‐6acompounds demonstrated MIC values againstStreptococcus faecalisandEscherichia coliequal to 3.91 and 7.81 μg/mL, respectively. Moreover, azo compound6ashowed MIC value equal to 3.91 μg/mL againstEnterobacter cloacaespecies. Additionally, derivative4fexhibited a significant inhibitory profile against theE. coligyrase A enzyme (IC50 = 5.53 μg/mL). On the other hand, compound6a(IC5014.05 μg/mL) exhibited the lowest DNA gyrase inhibitory activity as compared to compounds4fand reference standard drug novobiocin, IC505.53 and 1.88 μg/mL, respectively. Pharmacokinetic and pharmacodynamic profiles and molecular docking studies for the two most promising molecules4fand6awere computed and revealed that both compounds have good ADME profiles and high binding affinity to DNA gyrase binding site.