Substituted tolans for the modulation of microbial colonization
Described are methods for disinfecting a physical or biological surface by contact with an antimicrobial formulation comprising a compound having the structure (I): or a salt thereof, wherein each R 1 is independently C 1 -C 6 (halo) p alkyl, C 1 -C 6 alkyl-RH, OH, OC 1 -C 6 alkyl, or SH; each R 2 is independently C 1 -C 6 (halo) p alkyl, C 1 -C 6 alkyl-RH, OH, OC 1 -C 6 alkyl, or SH; each R is independently O or S; m is 1, 2, 3; n is 1, 2, or 3; and each p is independently 1, 2, or 3; provided that the compound having the structure (I) is mixed into an alcohol gel, and is not 3, 4′,5-trihydroxytolan. The compounds and methods are -static and/or -cidal, depending on dose and suspected microbe. Suspected pathogenic microbes include Gram negative bacteria, such as P. aeruginosa and E. coli , Gram positive bacteria, such as S. aureus , including MRSA, and fungal pathogens, such as Candida genus and C. albicans . Also described are methods for inhibiting or disrupting biofilm formation of a microbe or microbes.
1 . An antimicrobial formulation comprising an antimicrobially effective amount of a compound having the structure (I):
or a salt thereof,
wherein:
each R 1 is independently C 1 -C 6 (halo) p alkyl, C 1 -C 6 alkyl-RH, OH, OC 1 -C 6 alkyl, or SH;
each R 2 is independently C 1 -C 6 (halo) p alkyl, C 1 -C 6 alkyl-RH, OH, OC 1 -C 6 alkyl, or SH;
each R is independently O or S;
m is 1, 2, or 3;
n is 1, 2, or 3; and
each p is independently 1, 2, or 3;
with the provisos that:
(1) the compound having the structure (I) is mixed into an alcohol gel; and
(2) the compound having the structure (I) is not:
2 . The antimicrobial formulation of claim 1 , wherein the antimicrobial formulation is phenol free.
3 . The antimicrobial formulation of claim 1 , wherein the antimicrobial formulation comprises the compound having the structure (I), or a salt thereof, mixed into a 35% v/v alcohol gel.
4 . The antimicrobial formulation of claim 1 , wherein the antimicrobial formulation comprises a concentration of the compound having the structure (I), or a salt thereof, in an amount ranging from 2 mM to 44 mM.
5 . The antimicrobial formulation of claim 1 , wherein the antimicrobial formulation comprises a concentration of the compound having the structure (I), or a salt thereof, in an amount ranging from 0.008 mM to 1 mM.
6 . The antimicrobial formulation of claim 1 , wherein the antimicrobial formulation comprises a concentration of the compound having the structure (I), or a salt thereof, in an amount ranging from 0.01% w/w to 30% w/w.
7 . The antimicrobial formulation of claim 1 , wherein the antimicrobial formulation comprises a concentration of the compound having the structure (I) in an amount ranging from 0.25% w/v to 1% w/v.
8 . The antimicrobial formulation of claim 1 , wherein the compound having the structure (I) is:
or a salt thereof.
9 . The antimicrobial formulation of claim 8 , wherein the antimicrobial formulation comprises the compound having the structure (I), or a salt thereof, mixed into a 70% v/v alcohol gel.
10 . The antimicrobial formulation of claim 8 , wherein the antimicrobial formulation comprises a concentration of the compound having the structure (I), or a salt thereof, in an amount ranging from 2 mM to 44 mM.
11 . The antimicrobial formulation of claim 8 , wherein the antimicrobial formulation comprises a concentration of the compound having the structure (I), or a salt thereof, in an amount ranging from 0.008 mM to 1 mM.
12 . The antimicrobial formulation of claim 8 , wherein the antimicrobial formulation comprises the compound having the structure (I), or a salt thereof, at a concentration of 0.0625 mM.
13 . The antimicrobial formulation of claim 8 , wherein the antimicrobial formulation comprises the compound having the structure (I), or a salt thereof, at a concentration of 0.008 mM.
14 . The antimicrobial formulation of claim 8 , wherein the antimicrobial formulation comprises a concentration of the compound having the structure (I), or a salt thereof, in an amount ranging from 0.01% w/w to 30% w/w.
15 . The antimicrobial formulation of claim 1 , wherein the antimicrobial formulation further comprises an antibiotic.
16 . The antimicrobial formulation of claim 1 , wherein the antimicrobial formulation further comprises a solvent.
17 . The antimicrobial formulation of claim 1 , wherein the antimicrobial formulation further comprises a detergent, an emollient, a soap, or a surfactant.
18 . The antimicrobial formulation of claim 1 , wherein the antimicrobial formulation further comprises PEG-400 and hydroxypropyl-β-cyclodextrin in water.
19 . The antimicrobial formulation of claim 18 , wherein:
(a) the compound having the structure (I) is:
or a salt thereof; and
(b) the compound, or salt thereof, is mixed into a 70% v/v alcohol gel.
20 . The antimicrobial formulation of claim 1 , wherein the antimicrobial formulation further comprises:
(a) 30% v/v PEG-400;
(b) hydroxypropyl-β-cyclodextrin in water in an amount ranging from 0% to 28%;
(c) the compound having the structure (I):
or a salt thereof; and
(d) the compound, or salt thereof, mixed into a 70% v/v alcohol gel.