Zinc Complexes of Cationic Ammonium Phenyl and Methylpyridinium Porphyrins Display Synergistic Anti-HIV‑1 and Broad-Spectrum Antibacterial Activity.

This study presents a pioneering series of cationic porphyrins with promising synergistic antimicrobial and anti-HIV properties, particularly effective against drug-resistant strains. The synthesized porphyrins, including P 3 AmM, PAm 3 M, and c-P 2 Am 2 M, as well as their zinc-(II) complexes (P 3 AmZM, PAm 3 ZM, and c-P 2 Am 2 ZM), were developed through strategic methylation of primary amino groups in precursor porphyrins, addressing steric challenges associated with repetitive amine alkylation. Under photodynamic therapy (PDT) conditions, these compounds exhibited notable suppression of HIV-1 entry and infection, in addition to demonstrating potent antibacterial activity against drug-resistant Escherichia coli and Staphylococcus aureus. Bacterial growth kinetics indicated reduced proliferation and biofilm formation over a five-day period, underscoring their efficacy as antibacterial agents. Compounds P 3 AmZM, PAm 3 ZM, c-P 2 Am 2 M, c-P 2 Am 2 ZM, and PAm 3 M displayed enhanced antibacterial potency, with S. aureus showing greater susceptibility. Disc diffusion assays further confirmed the superior efficacy of c-P 2 Am 2 M and c-P 2 Am 2 ZM, particularly against S. aureus. Computational molecular docking simulations highlighted the robust binding affinity and interaction profiles of c-P 2 Am 2 M and c-P2Am 2 ZM with key HIV targets. These findings position these novel cationic porphyrins as potential dual-action therapeutics, combining synergistic anti-HIV efficacy with potent antibacterial activity under PDT conditions.