Home – Home – Jornals – Chemistry for Sustainable Development 2026 number 1

Antimicrobial resistance (AMR) constitutes one of the foremost threats to global public health in the XXI century: according to the data of the World Health Organization for 2025, one of the six laboratory-confirmed bacterial infections exhibits resistance to standard antibiotic therapy, with annual resistance rates increasing by 5-15 % across more than 40 % of pathogen-antibiotic combinations. Amid the declining efficacy of single-target antibiotics, the development of multitarget hybrid antibacterial agents - single molecules incorporating two or more pharmacophoric moieties capable of simultaneously engaging distinct bacterial targets - has gained critical relevance. This review systematically outlines the principal strategies for designing such hybrids: linked, fused, and merged pharmacophores. It also addresses key pharmacokinetic and toxicological considerations, limitations inherent to conventional combination therapy, and the advantages conferred by hybrid molecules, including a unified pharmacokinetic profile, elimination of chemical incompatibilities between components, and simplified dosing regimens. Particular emphasis is placed on the mechanisms of action of hybrid compounds. Several reviewed hybrids demonstrate low minimum inhibitory concentrations, reduced frequencies of spontaneous resistance emergence, and favourable fractional inhibitory concentration indices (FIC ≤ 0.5), underscoring the therapeutic potential of this approach. Some examples of compounds are highlighted for their potent activity against diverse resistant bacterial strains and biofilms. A number of hybrid compounds have successfully advanced through clinical trials (TNP-2092, TNP-2198, cefilavancin, DNV-3837).