Phytochemical Profiling and Antibacterial Activity of Moroccan Monofloral Honeys Against Multidrug‐Resistant Uropathogens: In Vitro, ADMET , Molecular Docking, and Molecular Dynamics Approaches

Abstract

ABSTRACT Urinary tract infections represent a significant public health issue exacerbated by bacterial antibiotic resistance. Honey, due to its phenolic compounds, offers a promising natural alternative. This study explores the phenolic profile of monofloral honeys from the Beni Mellal‐Khenifra region and their antibacterial activity against multidrug‐resistant strains. Four monofloral honeys from Beni Mellal‐Khenifra were analyzed for their phenolic composition and evaluated for antibacterial activity against multidrug‐resistant uropathogenic bacteria. Computational studies were also performed to explore the potential mechanisms of action of the identified compounds. HPLC‐UV detection identified distinct phenolic profiles in four monofloral honeys. Carob honey showed the highest diversity, with eight compounds identified, notably myricetin (63.99 μg/mg), trans‐ferulic acid (33.99 μg/mg), gallic acid (21.02 μg/mg), naringin (17.95 μg/mg), catechin (3.66 μg/mg), and trans‐cinnamic acid (2.75 μg/mg). Euphorbia honey was rich in hydroxycinnamic acids, especially caffeic acid (285.35 μg/mg), p‐coumaric acid (190.93 μg/mg), and trans‐ferulic acid (125.37 μg/mg). Anise honey contained high levels of naringin (669.84 μg/mg), along with myricetin (90.08 μg/mg) and 3‐hydroxybenzoic acid (76.59 μg/mg). In contrast, citrus honey exhibited the lowest polyphenolic content, with only gallic acid (0.21 μg/mg) and catechin (2.69 μg/mg) detected. The honey samples exhibited notable antibacterial activity against multidrug‐resistant uropathogenic bacteria, including E. coli , K. pneumoniae , and S. aureus . Among them, euphorbia and carob honeys demonstrated the highest antibacterial efficacy, with MBC values of 25% (v/v) against S. aureus and 50% against E. coli and K. pneumoniae . In contrast, citrus and anise honeys showed lower bactericidal activity, with MBC values reaching 75% (v/v) for E. coli and K. pneumoniae , and 50% for S. aureus . In silico, analyses showed that kaempferol, quercetin, catechin, and myricetin exhibit high binding affinities (up to −8.3 kcal/mol) against major bacterial targets. Molecular dynamics confirmed the stability of the quercetin‐GyrB complex (RMSD ~0.35 nm). ADMET and toxicity profiles identified catechin and 3‐hydroxybenzoic acid as the most promising candidates, combining good intestinal absorption, low predicted toxicity (LD50≈10,000 mg/kg), and favorable pharmacokinetics. These findings confirm the important role of honey's phenolic compounds in inhibiting multidrug‐resistant bacteria. Future research should focus on in vivo validation and the formulation of effective therapeutic products based on these honeys.