Inhibitors of multidrug transporters

An indole having the general formula:

• 49
• wherein R1 is phenyl, 2-naphthyl, o-anisole, R2 is H or CH3, R1 and R2 are two naphthyl groups fused to the indole ring, R3 is H, R4 is NO2, SO3H, NH2 and CF3 or CCl3, R5 is H, and R6 is H.

A urea having the general formula:

• 50
• wherein R1 is OR, Br, Cl, or F, R2 is OR, NHCO2R, Cl, F, or H, R3 is Cl, Br, OR, or CO2R, R4 is Cl or Br, R5 is H, R6 is H, R7 is H, R8 is a conjugated or aromatic system, R9 is H, OR, Cl or Br, R10 is H, OR, or Cl.

An aromatic amide having the general formula:

• 51
• wherein R1, R4 and R5 are H;
• R2 and/or R3 are small electron withdrawing groups, and R6 is substituted or unsubstituted alkyl of at least six atoms including C, O, N or S, with or without a phenyl ring.

A quinoline having the general formula:

• 52
• wherein R2 is 3,4-dimethoxybenzene, R3 is H, R4 is CO2R, C(═O)NHR, or NHC(═O)R, R5 is H, R6 is H, NO2, SO3H, NH2, CF3 or CCl3, R7 is an alkyl group, NO2, SO3H, NH2, CF3 or CCl3 and R8 is H.

A method for treating a subject with a bacterial infection comprising providing to said subject a fluoroquinolone and an inhibitor of NorA, wherein said inhibitor is an indole, a urea or an aromatic amide.

A pharmaceutical composition comprising a fluoroquinolone and an inhibitor of NorA, wherein said inhibitor is an indole, a urea or an aromatic amide.

A method of enhancing the antifungal action of azole antifungal agents comprising contacting a fungus with an inhibitor of a fungal multidrug transport protein, wherein said inhibitor is an indole, a urea or an aromatic amide.

A method of treating a subject with a fungal infection comprising providing to said subject an azole antifungal agent and an inhibitor of a fungal multidrug transport protein, wherein said inhibitor is an indole, a urea, or an aromatic amide.

A pharmaceutical composition comprising an azole antifungal agent and an inhibitor of a fungal multidrug transporter, wherein said inhibitor is an indole, a urea, or an aromatic amide.

A method for suppressing the emergence of fluoroquinolone resistance in bacteria, comprising contacting a bacterium with an efflux inhibitor, wherein said inhibitor is an indole, a urea, an aromatic amide or a quinoline.