2024-01-20 02:29:24
Its dual mechanism of action and its synergy with other antibiotics offer a solid basis for the development of more effective antimicrobial therapies.
Researchers at the Shanghai Engineering Research Center of Immunotherapeutics are developing an inhibitor of New Delhi metallo-beta-lactamase-1 (NMD-1), an enzyme that provides antibiotic resistance to multiple microorganisms that is currently expanding throughout the world and is associated with poor prognosis. The inhibitor (ASN-1733) has been identified in the screening of multiple nitroxoline derivatives, characterized by its ability to compete for calcium on the bacterial surface, resulting in the separation of lipopolysaccharide and destabilization of the membrane. Its oral effectiveness has been demonstrated in models of mild abdominal infection, soft tissue infection and sepsis.
Meiqing Feng, director of the study, states that the activity of ASN-1733 in these models was superior to that of nitroxoline, also showing a synergistic effect with meropenem against bacteria that express NMD-1. Notably, ASN-1733 was devoid of systemic toxicity, as revealed by dose escalation experiments in four treatment cycles, in which animals maintained their normal weight.
Safety
Feng points out that the safety of the compound was also reflected in the histological examination of multiple organs. Furthermore, the generation of resistance against ASN-1733 was considerably lower than that of other antibiotics, as can be seen from observations made on bacterial cultures exposed to low doses for 20 days. Under these conditions, the acquisition of resistance was less frequent than that observed with meropenem or colistin, says Feng. Taken together, the findings indicate that ASN-1733 exhibits the effectiveness and safety parameters necessary for its further development as an antibiotic, the researchers conclude. Rv: Ana Mera, pharmacist. Barcelona
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