Inhibitor for V-ATPase activity, antibacterial agent, medicine, antibacterial method and screening method

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, comprising the step of:

• administering a medicine to the subject having the bacterial flora containing the bacterium having V-ATPase and the bacterium having no V-ATPase, wherein the medicine comprises:
• a compound represented by the following formula (2) in an amount ranging from 1 μM to 100 mM:
• where R1 represents a group selected from a hydroxy group represented by —OH;
• a haloalkoxy group represented by —O—R1b—Xn1, wherein Rib is an alkyl group having 1 to 3 carbon atoms, X is a halogen selected from fluorine, chlorine, bromine, and iodine, and n1 is 1 to 3;
• a dialkylamino group represented by —N(R1c)(R1a), wherein R1c and R1d are each independently an alkyl group having 1 to 10 carbon atoms and may be the same or different from each other;
• a heterocyclic amine having 2 to 6 carbon atoms represented by —N—(CH2)n2—, wherein n2 is 2 to 6;
• bromine represented by —Br;
• iodine represented by —I;
• or a straight-chain hydrocarbon group having 2 to 5 carbon atoms represented by —(CH2)n3—CH3, wherein n3 is 1 to 4;
• R2 represents hydrogen or a haloalkoxy group represented by —O—R2a—Xn4, wherein R2a is a hydrocarbon group having 1 to 3 carbon atoms, X is a halogen selected from fluorine, chlorine, bromine, and iodine, and n4 is 1 to 3;
• and
• R3 and R4 represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a halogen atom selected from fluorine, chlorine, bromine, and iodine, and R3 and R4 may be the same as or different from each other, and
• an additive, wherein the additive is a solvent, an excipient, a binding agent, a disintegrant, a lubricating agent, a stabilizer, or a suspending agent;
• wherein 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 of the V-ATPase 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,
• wherein the bacterium having V-ATPase is Chlamydia trachomatis, Mycobacterium abscessus, Enterococcus faecium, Enterococcus durans, Enterococcus munditi, Enterococcus faecalis, Enterococcus malodoratus, Enterococcus cecorum, Enterococcus casseliflavus, Streptococcus agalactiae, Streptococcus sanguinis, Streptococcus constellatus, Streptococcus intermedius, Streptococcus gallolyticus, Streptococcus parasanguinis, Streptococcus anginosus, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus pseudopneumoniae, Streptococcus mitis, Streptococcus canis, Streptococcus urinalis, Clostridium botulinum, Clostridium baratii, Clostridium argentinense, Clostridium chauvoei, Clostridium intestinale, Clostridium paraputrificum, Clostridium perfringens, Clostridium tetani, Clostridium difficile, Fusobacterium nucleatum, Fusobacterium necrophorum, Fusobacterium periodonticum, Abiotrophia defective, Aerococcus urinae, Aerococcus viridans, Facklamia hominis, Facklamia languida, Facklamia ignava, Facklamia sourekii, Alloiococcus otitis, Dolosigranulum pigrum, Granulicatella elegans, or Anaerotruncus colihominis.