Inhibitor for V-ATPase activity, antibacterial agent, medicine, antibacterial method and screening method
Inventors
Murata, Takeshi • Shimizu, Kouki • Yakushiji, Fabiana Lica • Moriyama, Katsuhiko
Assignees
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Publication Number
US-12599588-B2
Publication Date
2026-04-14
Expiration Date
Abstract
An inhibitor for Na+-translocating V-ATPase activity including a compound represented bywhere R1 represents a group selected from a hydroxy group, an alkoxy group, and a haloalkoxy group, each bonded to an adjacent phenyl group via oxygen, or a group selected from a dialkylamino group, a heterocyclic amine, and a carboxylic acid amide group, each bonded to an adjacent phenyl group via nitrogen, or represents bromine, iodine, or a straight-chain hydrocarbon group. R2 represents hydrogen or a haloalkoxy group. Z1 represents an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an aromatic hydrocarbon group, or a heterocyclic group, each optionally having an arbitrary substituent and having a structure containing a double bond selected frombetween the group and an adjacent phenyl group. The symbol * represents a bond to the adjacent phenyl group.
Core Innovation
The invention relates to V-ATPase (Na+-translocating) inhibitory antibacterial agents and a medicine for suppressing growth of bacteria having V-ATPase in a subject. The inhibitor is a compound represented by formula (2) and related structural examples, and the disclosed structure includes a phenyl group bearing an electron-donating group and an arbitrary substituent Z1 linked via specified double-bond-containing linkers.
The compound represented by formula (2) binds to a membrane-embedded rotor ring (c ring) of the V-ATPase of the bacterium to inhibit a Na+-translocating activity. Disease-causing bacteria require V-ATPase (Na+-translocating activity) for growth, including in alkaline conditions and/or high-salt conditions, and the stated goal is to selectively and efficiently suppress disease-causing bacteria by administering a Na+-translocating V-ATPase inhibitor.
The invention also defines bacterial flora control contexts, including suppressing the bacterium having V-ATPase from bacterial flora that contains bacteria having V-ATPase and bacteria having no V-ATPase. The partial content further describes the medicine as including an additive selected from a solvent, excipient, binding agent, disintegrant, lubricating agent, stabilizer, or suspending agent.
Claims Coverage
The partial claims provided include two independent claims. Across these claims, the inventive coverage centers on administering a formula (2) compound in an amount ranging from 1 μM to 100 mM that binds the V-ATPase membrane-embedded c ring to inhibit Na+-translocating activity, either to suppress growth of V-ATPase-positive bacteria generally or to selectively reduce V-ATPase-positive bacteria within a bacterial flora containing bacteria lacking V-ATPase.
Administering a formula (2) medicine to suppress growth of V-ATPase-having bacteria by c-ring binding and Na+-translocating inhibition
A method of suppressing growth of a bacterium having V-ATPase in a subject by administering a medicine comprising a compound represented by formula (2) in an amount ranging from 1 μM to 100 mM, where the compound binds to a membrane-embedded rotor ring (c ring) of the V-ATPase of the bacterium to inhibit a Na+-translocating activity, and the medicine further includes an additive selected from a solvent, excipient, binding agent, disintegrant, lubricating agent, stabilizer, or suspending agent.
Administering a formula (2) medicine to selectively reduce V-ATPase-having bacteria within bacterial flora by c-ring binding and Na+-translocating inhibition
A method of suppressing growth of a bacterial flora containing a bacterium having V-ATPase and a bacterium having no V-ATPase in a subject by administering a medicine comprising a compound represented by formula (2) in an amount ranging from 1 μM to 100 mM, where the compound binds to a membrane-embedded rotor ring (c ring) of the V-ATPase of the bacterium to inhibit a Na+-translocating activity to selectively reduce the bacterium having V-ATPase from the bacterial flora containing the bacterium having V-ATPase and the bacterium having no V-ATPase, and the medicine further includes an additive selected from a solvent, excipient, binding agent, disintegrant, lubricating agent, stabilizer, or suspending agent.
Both independent claims cover administration of a medicine containing a compound of formula (2) that binds the V-ATPase membrane-embedded c ring to inhibit Na+-translocating activity, with one claim addressing suppressing growth of V-ATPase-having bacteria in a subject and the other addressing selective reduction within bacterial flora that also includes bacteria having no V-ATPase.
Stated Advantages
The inhibitor binds to the membrane-embedded rotor ring (c ring) to inhibit a Na+-translocating activity of the V-ATPase.
The method suppresses growth of bacteria having V-ATPase in a subject.
In bacterial flora, the method selectively reduces bacteria having V-ATPase from flora containing bacteria having V-ATPase and bacteria having no V-ATPase.
Documented Applications
Antibacterial agent use to suppress growth of a bacterium having V-ATPase in a subject by administering a V-ATPase (Na+-translocating) inhibitory compound of formula (2).
Bacterial flora control agent use to suppress growth and selectively reduce the bacterium having V-ATPase from bacterial flora containing both V-ATPase-positive and V-ATPase-negative bacteria in a subject.
Screening method concept for identifying compounds that alter a living state of bacteria under alkaline pH conditions by comparing bacterial viability with and without candidate compounds.
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