Thiazole-pyrazoline hybrids as potential antimicrobial agent: Synthesis, biological evaluation, molecular docking, DFT studies and POM analysis

In this study, an efficient synthesis of new thiazole-pyrazoline hybrids was investigated and hybrids were screened for their antimicrobial activities against four species of pathogenic bacteria and one fungal strain utilizing the well-diffusion and MIC assays using ciprofloxacin and fluconazole as the positive controls. The obtained results revealed excellent to moderate antibacterial and antifungal activity. Among them, compound 11b showed potent antibacterial activity against A. baumannii with MIC of 16 mu g/mL, while ciprofloxacin was ineffective. Molecular docking studies showed that compound 11b had a stronger bind -ing affinity of about 1 kcal/mol to gram-positive and gram-negative bacteria than compared with com-pound 11a . Furthermore, the results of the POM (Petra, Osiris, Molinspiration) bioinformatics investiga-tions show that the two studied heterocycles present a very good non toxicity profile, a bad bioavail-ability, and pharmacokinetics. Finally, an antibacterial pharmacophore (N8-, HN8-) and two antifungal pharmacophores (N8-, S8-) and (N8-, N8-) were evaluated in the POM investigations and deserves all our attention to be tested against other pathogenic microorganisms. The more potent compound 11b com-pared to that of 11a can also be attributed to its lower HOMO-LUMO gap which is an indicator of greater reactivity.(c) 2023 Elsevier B.V. All rights reserved.