Fig. 1: Dual-mechanism approaches. | Nature Microbiology

Fig. 1: Dual-mechanism approaches.

From: Dual-mechanism antibiotics

Fig. 1

The main goals of dual-mechanism strategies include broadening the spectrum of action, achieving synergistic activities, delaying emergence of resistance, protecting against specific resistance determinants and facilitating penetration in the Gram-negative cell. Individual chemical entities (comprised of either two antibacterial-acting molecules, or one antibiotic plus one enabling compound) could be co-formulated (a) or linked by a metabolically cleavable bond to form a prodrug hybrid (b). Both approaches lead to independent and potentially unpredictable PK and PD. A metabolically stable link provides a single PK and PD profile if not degraded by bacterium-specific enzymes (c). A single dual-mechanism molecule or fused functional pharmacophoric entities have singlular PK and PD characteristics (d).

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