Reducing tetracycline resistance in living cells
View Patent ↗The present invention provides an improved methodology by which therapeutically to overcome resistance to tetracycline in living cells including bacteria, parasites, fungi, and rickettsiae. The methodology employs a blocking agent such as C5 ester derivatives, or 6-deoxy 13-(substituted mercapto) derivatives of tetracycline, in combination with other tetracycline-type antibiotics as a synergistic combination of compositions to be administered simultaneously, sequentially or concurrently. In another embodiment, certain novel compositions are provided which may be administered alone against, for example, a sensitive or resistant strain of gram positive bacteria such as S. aureus and E. faecalis . The concomitantly administered compositions effectively overcome the tetracycline resistant mechanisms present such that the cell is effectively converted from a tetracycline-resistant state to a tetracycline-sensitive state.
1. A compound having the formula
wherein
A is hydroxyl,
B is hydrogen or a morpholino group, and
R is alkyl, arylalkyl, or aryl.
2. The compound of claim 1 , wherein R is ethyl, propyl, isopropyl, butyl, t-butyl, isobutyl, cyclopentyl, hexyl, decyl, cyclohexyl, benzyl, p-chloro-benzyl, p-methyl-benzyl, or dihydroxypropyl.
3. The compound of claim 1 , wherein R is decyl.
4. The compound of claim 1 , wherein R is hexyl.
5. The compound of claim 1 , wherein R is benzyl.
6. The compound of claim 1 , wherein R is p-chloro-benzyl.
7. The compound of claim 1 , wherein R is p-methyl-benzyl.
8. The compound of claim 1 , wherein R is cyclopentyl.
9. The compound of claim 1 , wherein R is butyl.
10. The compound of claim 1 , wherein R is t-butyl.
11. The compound of claim 1 , wherein R is isobutyl.
12. The compound of claim 1 , wherein R is propyl.
13. The compound of claim 1 , wherein R is isopropyl.
14. The compound of claim 1 , wherein R is dihydroxypropyl.
15. The compound of claim 1 , wherein R is ethyl.
16. The compound of claim 1 , wherein R is cyclohexyl.