Methods of treating microbial infections in humans and animals
A method of treating a subject with a microbially-based infection, comprising the administration of a compound to the subject. The compound is able to decrease ATP levels in the microbe by at least 10% compared to controls after 24 hours in an in vitro test, without killing mammalian cells during the same time period. The decrease in ATP levels is measured by: (1) removing the cells from the testing location and putting them on ice; (2) harvesting the cells at 4 degrees C. by centrifugation and disrupting it with bead-beating in an ATP extraction buffer; (3) removing cellular debris by centrifugation at 4 degrees C., leaving an ATP-containing supernatant; (4) measuring the amount of ATP present in the supernatant by a bioluminescence assay at 4 degrees C.
1 . A method of treating a subject with a microbially-based infection, comprising the administration of an effective amount of a compound to a subject in need of treatment, the compound being able to decrease ATP levels in the microbe by at least 10% compared to controls after 24 hours in an in vitro test, and not kill mammalian cells during the same time period, the decrease in ATP levels being measured by:
(1) removing the cells from the testing location and putting them on ice;
(2) harvesting the cells at 4 degrees C. by centrifugation and disrupting it with bead-beating in an ATP extraction buffer;
(3) removing cellular debris by centrifugation at 4 degrees C., leaving an ATP-containing supernatant;
(4) measuring the amount of ATP present in the supernatant by a bioluminescence assay at 4 degrees C.;
wherein the compound is not of formula R—SO n -Z-CO—Y, wherein n is 1 or 2, R is a hydrocarbon group having 6-20 carbon atoms, Z is a hydrocarbon linking moiety that may contain a heteroatom, and Y is selected from —NH, —O—CH 2 —C 6 H 5 , —CO—CO—O—CH 3 , and —O—CH 3 .
2 . The method of claim 1 , wherein the subject is a human.
3 . The method of claim 1 , wherein the subject is an animal.
4 . The method of claim 3 , wherein the subject is selected from the group consisting of horses, cattle, goats and sheep.
5 . The method of claim 1 , wherein the compound is selected from the group consisting of:
6 . The method of claim 5 , wherein the compound is
7 . The method of claim 5 , wherein the compound is
8 . The method of claim 5 , wherein the compound is
9 . The method of claim 5 , wherein the compound is
10 . The method of claim 5 , wherein the compound is
11 . The method of claim 5 , wherein the compound is
12 . The method of claim 5 , wherein the compound is
13 . The method of claim 5 , wherein the compound is
14 . The method of claim 1 , wherein the subject is infected with a microbe selected from the group consisting of M. tuberculosis, M. avium - intracellulare, M. leprae, M. paratuberculosis, M. ulcerans , and Rhodococcus.
15 . A method of treating a subject with a microbially-based infection, comprising the administration of a compound to a subject in need of treatment, wherein the compound produces overexpression of the b-subunit of ATP synthase, and further wherein the compound is not of formula R—SO n -Z-CO—Y, wherein n is 1 or 2;
R is a hydrocarbon group having 6-20 carbon atoms, Z is a hydrocarbon linking moiety that may contain a heteroatom, and Y is selected from —NH, —O—CH 2 —C 6 H 5 , —CO—CO—O—CH 3 , and —O—CH 3 .
16 . The method of claim 15 , wherein the subject is a human.
17 . The method of claim 15 , wherein the subject is an animal.
18 . The method of claim 17 , wherein the subject is selected from the group consisting of horses, cattle, and sheep.
19 . The method of claim 15 , wherein the compound is selected from the group consisting of:
20 . The method of claim 19 , wherein the compound is
21 . The method of claim 19 , wherein the compound is
22 . The method of claim 19 , wherein the compound is
23 . The method of claim 19 , wherein the compound is
24 . The method of claim 19 , wherein the compound is
25 . The method of claim 19 , wherein the compound is
26 . The method of claim 19 , wherein the compound is
27 . The method of claim 19 , wherein the compound is