DIPHENYL (PIPERIDIN-4-YL) METHANOL DERIVATIVES AS POTENTIAL CANDIDATES FOR ANTIFUNGAL AND ANTIBACTERIAL ACTIVITIES: SYNTHESIS, SPECTRAL CHARACTERIZATION, AND IN-VITRO STUDY

Abstract WHO has declared Antimicrobial resistance (AMR) as one of the top global public health and developmental threats. The rising challenge of multidrug resistance (MDR) underscores the urgent need for novel antimicrobial agents to combat infections. In this study, we explored the chemistry of Diphenyl(piperidin-4-yl)methanol (DPP) and its substituted molecules within a unified molecular framework by synthesizing six new derivatives through the alkylation of the piperidine nitrogen of DPP with various phenacyl halides. The structures of these derivatives were elucidated using EIMS, ¹H-NMR, UV, and FTIR techniques. Agar well disc diffusion method was used to evaluate the antibacterial and antifungal activities of synthesized compounds. Antibacterial assay showed significant zones of inhibition (ZOI ≥ 12 mm) against various bacterial strains. Notably, 4NP and DCP were highly effective against Proteus mirabilis, which causes urinary tract infections and related complications. 4NP also demonstrated significant activity against Staphylococcus aureus and Enterobacter DCP was notably effective against Shigella dysenteriae, responsible for shigellosis. In antifungal assays, 3NP, 4NP, DHP, and DCP surpassed fluconazole in ZOI against various fungal strains. 3NP showed superior inhibition against Candida albicans, indicating potential for treating candidiasis. DCP was effective against Penicillium spp., suggesting potential for treating penicilliosis. 4NP was the most potent, particularly against Aspergillus niger, with a ZOI of 25 mm, nearly double that of fluconazole. SAR analysis indicated that nitro and hydroxyl substitutions enhanced inhibition potential, especially at the para position. The study concludes that the lead molecule DPP and its derivatives, especially 4NP and DCP, exhibit promising antibacterial and antifungal activities, making them potential candidates for treating various infections. Further optimization and in vivo studies are recommended to realize their clinical potential fully.