Use of branched chain fatty acids and derivatives thereof for inhibition of P-glycoprotein

A method for treatment of a tumor associated with increased activity of P-glycoprotein comprising administering to a patient in need thereof an effective amount of a compound of the following general formula I in combination with an anti-cancer drug, whereby cells of said tumor having P-glycoprotein are contacted with said compound of the following general formula I,

• wherein
• R1 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 1 to 10 carbon atoms;
• R2 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 5 to 30 carbon atoms;
• A is selected from the group consisting of C(O)OH, C(O)O—R′, C(O)NH2, C(O)NH—R′, and C(O)O−Y+, wherein R′ is a lower alkyl group comprising 1-5 carbon atoms, and Y denotes any pharmaceutically acceptable counter-ion.

A method for administration of diagnostic agents into cells associated with increased activity of P-glycoprotein comprising contacting said cell having P-glycoprotein with a diagnostic agent in the presence of an effective amount of a compound of the following general formula I, thus enabling or increasing the penetration and/or accumulation of the diagnostic agent in the cells,

• wherein
• R1 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 1 to 10 carbon atoms;
• R2 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 5 to 30 carbon atoms;
• A is selected from the group consisting of C(O)OH, C(O)O—R′, C(O)NH2, C(O)NH—R′, and C(O)O−Y+, wherein R′ is a lower alkyl group comprising 1-5 carbon atoms, and Y denotes any pharmaceutically acceptable counter-ion.

A method for increasing accumulation of a diagnostic agent in an organ protected by a biological barrier comprising administering to an individual said diagnostic agent in combination with an effective amount of a compound of the following general formula I, whereby cells of said biological barrier having P-glycoprotein are contacted with said compound of the following general formula I, thus increasing accumulation of the diagnostic agent in the organ protected by a biological barrier,

• wherein
• R1 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 1 to 10 carbon atoms;
• R2 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 5 to 30 carbon atoms;
• A is selected from the group consisting of C(O)OH, C(O)O—R′, C(O)NNH2, C(O)NH—R′, and C(O)O−Y+, wherein R′ is a lower alkyl group comprising 1-5 carbon atoms, and Y denotes any pharmaceutically acceptable counter-ion.

A method for administration of a biologically active molecule into cells associated with increased activity of P-glycoprotein comprising contacting said cells having P-glycoprotein with said biologically active molecule in the presence of an effective amount of a compound of the following general formula I, thus enabling or increasing the penetration and/or accumulation of the biologically active molecule in the cells,

• wherein
• R1 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 1 to 10 carbon atoms;
• R2 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 5 to 30 carbon atoms;
• A is selected from the group consisting of C(O)OH, C(O)O—R′,C(O)NH2, C(O)NH—R′, and C(O)O−Y+, wherein R′ is a lower alkyl group comprising 1-5 carbon atoms, and Y denotes any pharmaceutically acceptable counter-ion.

A method for increasing accumulation of biologically active molecules in an organ protected by a biological barrier comprising administering to an individual a biologically active molecule in combination with an effective amount of a compound of the following general formula I, whereby cells of said biological barrier having P-glycoprotein are contacted with said compound of the following general formula I, thus increasing accumulation of the biologically active molecule in the organ protected by a biological barrier,

• wherein
• R1 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 1 to 10 carbon atoms;
• R2 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 5 to 30 carbon atoms;
• A is selected from the group consisting of C(O)OH, C(O)O—R′, C(O)NHI2, C(O)NH—R′, and C(O)O−Y+, wherein R′ is a lower alkyl group comprising 1-5 carbon atoms, and Y denotes any pharmaceutically acceptable counter-ion.

A method for increasing bioavailability of a drug comprising administering to an individual said drug in combination with an effective amount of a compound of the following general formula I, whereby cells in said individual having P-glycoprotein are contacted with said compound of the following general formula I,

• wherein
• R1 is a saturated or unsaturated, substituted ox unsubstituted hydrocarbon chain having from 1 to 10 carbon atoms;
• R2 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 5 to 30 carbon atoms;
• A is selected from the group consisting of C(O)OH, C(O)O—R′, C(O)NH2, C(O)NH—R′, and C(O)O−Y+, wherein R′ is a lower alkyl group comprising 1-5 carbon atoms, and Y denotes any pharmaceutically acceptable counter-ion.

A method for increasing drug absorption through a biological barrier comprising administering to an individual a drug in combination with an effective amount of a compound of the following general formula I, whereby cells of said biological barrier having P-glycoprotein are contacted with said compound of the following general formula I, thus increasing the drug absorption through said biological barrier,

• wherein
• R1 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 1 to 10 carbon atoms;
• R2 is a saturated or unsaturated, substituted or unsubstituted hydrocarbon chain having from 5 to 30 carbon atoms;
• A is selected from the group consisting of C(O)OH, C(O)O—R′, C(O)NH2, C(O)NH—R′, and C(O)O−Y+, wherein R′ is a lower alkyl group comprising 1-5 carbon atoms, and Y denotes any pharmaceutically acceptable counter-ion.