In silico molecular docking studies of oxadiazole and pyrimidine bearing heterocyclic compounds as potential antimicrobial agents

Abstract

Microbial resistance is a major problem faced by the scientific community. It has created an urgent need to develop antimicrobial agents with novel structures and mechanisms of action. With this aim, a series of novel 1,3,4‐oxadiazoles bearing 3,4‐dihydropyrimidine heterocyclic motifs 4a–l were designed and synthesized. One‐pot Biginelli synthesis is pivotal due to the use of readily available chemicals, shorter reaction time, and ecofriendly synthesis with a good yield. The structures of the synthesized molecules were characterized and confirmed by infrared, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectroscopic techniques. The title compounds were screened against Gram‐positive and ‐negative strains of bacteria and fungi using the Mueller–Hinton broth method. Compound 4d was found to be the most promising against Escherichia coli (12.5 µg/ml), whereas the same compound showed good activity against Staphylococcus aureus at a concentration of 50 µg/ml. Other compounds of the same series, 4c and 4h, displayed moderate activity against Streptococcus pyogenes at a concentration of 50 µg/ml. Furthermore, results of the antifungal activity tests revealed that compound 4i showed promising activity against all the strains of fungi, Candida albicans, Aspergillus niger, and Aspergillus clavatus, at concentrations of 100, 50, and 100 µg/ml, respectively. Molecular docking also showed that these compounds had a significant binding affinity (Glide docking score: −7.74 to −6.531) for DNA gyrase, engaging in a series of bonded and nonbonded interactions with residues lining the active site. The results of molecular docking study validated the experimental findings, thereby providing an initiation mark to optimize this motif using a structure‐based drug design approach.

Conventional and microwave‐assisted organic synthesis of novel antimycobacterial agents bearing furan and pyridine hybrids

“…The scoring function is equipped with force field‐based parameters that account for contributions from steric and electrostatic interaction energies, solvation and repulsive interactions along with hydrophobic, hydrogen bonding, and metal–ligand interactions all incorporated in the empirical energy functions. Maestro's Pose Viewer utility was used to visualize and analyze the output file generated in terms of the docking poses of the ligands for the key elements of interaction with the enzyme” (Desai, Mehta, et al, 2021; Desai, Vaghani, et al, 2021).…”

“…"The molecular docking study was performed with Glide (Grid-Based Ligand Docking with Energetics) (Friesner et al, 2004;Halgren et al, 2004) ments of interaction with the enzyme" (Desai, Mehta, et al, 2021;Desai, Vaghani, et al, 2021).…”

“…Furan is an antitubercular compound with one oxygen atom in its moiety (Chiarelli et al, 2019; Kantevari et al, 2011; Yan et al, 2020; Yempala et al, 2014). By combining three hybrid motifs, we may expect the enhancement of the activity of synthesized compounds (5a‐o) (Desai et al, 2020; Desai, Mehta, et al, 2021; Desai, Vaghani, et al, 2021; Eryılmaz et al, 2020; Mejía‐Gutiérrez et al, 2020; Tan et al, 2020; Verma et al, 2020). The antitubercular activity of all newly synthesized compounds was assessed, and the structures of novel compounds were assigned using various spectroscopic techniques.…”

Oxadiazole: A highly versatile scaffold in drug discovery

“…Desai et al [ 30 ] prepared heterocyclic compounds bearing oxadiazole and pyrimidine as potential antimicrobial agents. Compound 161 possessed the most prominent activity against E. coli with a MIC value of 12.5 μg/ml and S. aureus with a MIC value of 50 μg/ml.…”

“…[ 7–14 ] The other heterocycles like pyrimidine, furan, pyrrole, indole, oxadiazole, benzoxazole, azetidine, thiophene, coumarin, benzofuran, pyrazole, quinoline oxazole, quinazoline, pyrimidine, thiazole, quinoline, pyrazole, and isoxazole also possess various pharmacological activities. [ 8,15–30 ]…”