Design, molecular docking, and antimicrobial assessment of newly synthesized phytochemical thymol Mannich base derivatives

•Synthesized and structural elucidation of Mannich based thymol congeners.•Antibacterial and antifungal activities were carried out against UTI bacteria and T. rubrum, C. tropicalis.•Compound 4-((dimethylamine)methyl)−2-isopropyl-5-methylphenol 4 g had shown potent antifungal action with MIC against 3.12 μg/mL T. rubrum.•Molecular docking and PreADMET was performed against viz., bacterial DHPS enzyme and fungal lanosterol C14α-Demethylase. Antibacterial resistance has been brewing for decades and has now surfaced into potential public health emergency, everywhere. Thus, newer potent drug candidates are needed urgently that would help overcoming antibiotic resistances in bacteria and fungi. A series of thymol-bearing amino methylated sulfonamide congeners, 4a-4l were designed and synthesized by the Mannich condensation reaction of the respective cyclic amines 3a-3 g, and N-heteroaryl- 4-amino benzenesulfonamide 3h-3l, with thymol and formaldehyde in an acidic medium. The synthesized compounds were structurally confirmed by spectroscopic studies; 1H/13C NMR, FTIR, ESI-HRMS, and elemental analysis. The powder characterization of the synthesized compounds was performed by XRD analysis. The obtained products were screened for antibacterial assay against uropathogenic bacteria, Staphylococcus aureus, Streptococcus pyogenes and Escherichia coli; and for antifungal assay with Candida tropicalis and Trichophyton rubrum. The results of antimicrobial activities of all compounds had exhibited moderate to excellent bacterial inhibition; whereas the compound 2-isopropyl-5-methyl-4-(pyrrolidin-1-ylmethyl)phenol, 4f had exhibited significant inhibition of E.coli and S. aureus with MIC 3.12 μg/ml, 12.5 μg/ml, respectively. The compound 4-((dimethylamino)methyl)-2-isopropyl-5-methylphenol, 4 g had a good inhibition against E. coli and S. aureus at MIC 6.25 μg/ml; and for T. rubrum at 3.12 μg/ml. The synthesized compounds 4 g and 4 h had the highest inhibition against the fungus, T. rubrum at inhibition with 27 and 28 mm, respectively. Thus, the synthesized compounds with methylated dimethylamino in thymol could be the potential lead candidates for antibacterial and antifungal actions. The binding affinity of the compounds had been evaluated by molecular docking with both bacterial and fungal target proteins and their physiological and ADME properties were assessed. [Display omitted]