Aspergillomarasmine A

Aspergillomarasmine A (AMA) potently and selectively inhibits the metallo-β-lactamases NDM-1 (IC₅₀ = 4 μM) and VIM-2 (IC₅₀ = 9.6 μM) in vitro, while it exhibits only extremely low activity against other metalloenzymes and no activity against serine β-lactamases. In addition, it inactivates NDM-1 and VIM-2 in vitro via a saturable metal depletion mechanism^[1].
Aspergillomarasmine A irreversibly inactivates purified NDM-1 via zinc depletion, and this inactivation can be reversed by the addition of excess zinc^[1].
Aspergillomarasmine A (AMA) selectively binds Zn²⁺, Ni²⁺, and Co²⁺, but does not bind Mg²⁺ or Ca²⁺, which are abundant in organisms; it exhibits extremely high affinity for Zn^2+[3].
Aspergillomarasmine A inhibits over 90% of the activity of purified NDM-1, and its inhibitory activity is blocked by Co²⁺, Ni²⁺ and Zn^2+[3].
Aspergillomarasmine A (0.01-20 mM) inactivates purified NDM-1 primarily via a Zn²⁺-chelating mechanism, which causes Zn²⁺ to dissociate from the Zn₂ site of purified NDM-1. After supplementation with Zn²⁺, the activity of NDM-1 is fully recoverable, and the inactivation rate is consistent with the spontaneous dissociation rate of Zn²⁺ from NDM-1^[3].
Aspergillomarasmine A enables biotinylation of the Cys₂₀₈ residue associated with the Zn₂ site in purified NDM-1, with a labeling efficiency of 80%, confirming the dissociation of Zn²⁺ from the Zn₂ site^[3].
Aspergillomarasmine A (2-64 μg/mL; 15 min) reduces the protein levels and β-lactamase activities of NDM-1, NDM-6, and IMP-7 in viable Escherichia coli in a variant-specific manner, with NDM-1 showing the highest sensitivity, NDM-6 moderate sensitivity, and IMP-7 the strongest resistance. This characteristic correlates with Zn²⁺ affinity and protein stability^[3].
Aspergillomarasmine A acts synergistically with Meropenem (HY-13678) to inhibit carbapenem-resistant Enterobacteriaceae expressing NDM-1; among the 16 tested clinical isolates, their fractional inhibitory concentration (FIC) indices are all < 0.1. Combination with Meropenem (2 μg/mL) restores Meropenem susceptibility in 88% of NDM-positive and 90% of VIM-positive clinical Gram-negative bacteria, including Pseudomonas strains^[1].
Aspergillomarasmine A stereoisomers display varied biological activities when combined with meropenem against drug‑resistant Klebsiella pneumoniae (BAA‑2146). Among these stereoisomers, (S,S,S)‑Aspergillomarasmine A (25 μM) delivers the most potent synergistic effect, yielding an FICI < 0.28 and an RC value of 25 μM^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.