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 6-deoxy-13-(substituted mercapto) tetracycline compound having the formula
wherein A is hydrogen or hydroxyl,
B is hydrogen or a morpholino group, and
R is alkyl, arylalkyl, or aryl.
2. The tetracycline compound of claim 1 , wherein R is ethyl, propyl, isopropyl, butyl, t-butyl, isobutyl, cyclopentyl, hexyl, decyl, cyclohexyl, benzyl, p-Cl-benzyl, p-Me-benzyl, or dihydroxypropyl.
3. The tetracycline compound according to claim 1 having the formula:
4. The tetracycline compound according to claim 1 having the formula:
5. The tetracycline compound according to claim 1 having the formula:
6. The tetracycline compound according to claim 1 having the formula:
7. The tetracycline compound according to claim 1 having the formula:
8. The tetracycline compound according to claim 1 having the formula:
9. The tetracycline compound according to claim 1 having the formula:
10. The tetracycline compound according to claim 1 having the formula:
11. The tetracycline compound according to claim 1 having the formula:
12. The tetracycline compound according to claim 1 having the formula:
13. The tetracycline compound according to claim 1 having the formula:
14. The tetracycline compound according to claim 1 having the formula:
15. The tetracycline compound according to claim 1 having the formula:
16. The tetracycline compound according to claim 1 having the formula:
17. The tetracycline compound according to claim 1 having the formula: