Indenopyridin‐5‐one derivatives containing azo groups and their hydrazonal precursors: Synthesis, antimicrobial profile, DNA gyrase binding affinity, and molecular docking

• Published in: Journal of heterocyclic chemistry 2024-02, Vol.61 (2), p.217-231
• Main Authors: Kassab, Refaie M, Muhammad, Zeinab A, Sami A Al‐Hussain, Zaki, Magdi E A, Ibrahim, Mona H, Alsaedi, Amani M R, Farghaly, Thoraya A
• Format: Article
• Language: English
• Subjects: Affinity; Antiinfectives and antibacterials; Antimicrobial agents; Azo compounds; Bacteria; Binding sites; E coli; Enterobacter cloacae; Fungicides; Hydrazones; Molecular docking; Molecular structure
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.4759

The 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 hydrazones 4a‐h and 6a‐g displayed 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 hydrazone 4f and azo‐6a compounds demonstrated MIC values against Streptococcus faecalis and Escherichia coli equal to 3.91 and 7.81 μg/mL, respectively. Moreover, azo compound 6a showed MIC value equal to 3.91 μg/mL against Enterobacter cloacae species. Additionally, derivative 4f exhibited a significant inhibitory profile against the E. coli gyrase A enzyme (IC50 = 5.53 μg/mL). On the other hand, compound 6a (IC50 14.05 μg/mL) exhibited the lowest DNA gyrase inhibitory activity as compared to compounds 4f and reference standard drug novobiocin, IC50 5.53 and 1.88 μg/mL, respectively. Pharmacokinetic and pharmacodynamic profiles and molecular docking studies for the two most promising molecules 4f and 6a were computed and revealed that both compounds have good ADME profiles and high binding affinity to DNA gyrase binding site.