Topical antimicrobial agents

A method to inhibit microbial growth is provided comprising topically administering to a mammal afflicted with a pathology associated with microbial growth, such as a dermatological condition, an effective amount of a linear (C.sub.12 -C.sub.22) 3-alken-2-one or 3,.omega.-alkadien-2-one.

BACKGROUND OF THE INVENTION 
The odorous compounds of plants are volatile and are usually separated from 
the plant material by steam distillation. They are known as the volatile 
or essential oils, and consist of hydrocarbons, alcohols, ethers aldehydes 
and ketones. In the evaluations of conifers and in the oils from citrus 
fruits and from eucalyptus trees, alicyclic hydrocarbons of the 
composition C.sub.10 H.sub.16 were found to be especially abundant, and it 
is to these compounds that the term "terpene" was applied in the 
restricted sense. It soon became evident, however, that compounds 
containing 15, 20, 30 and 40 carbon atoms also are closely related to 
terpenes, and the term "terpene" in its broadest sense now includes all 
such compounds, which comprise repeating iso-C.sub.5 units. 
Many of the essential oils are employed in various flavors and fragrances, 
and their medicinal or biocidal potential has been the subject of 
continued investigation. For example, the cyclic terpenones, 
.alpha.-ionone and .beta.-ionone, were reported to exhibit moderate 
antibacterial activity against S. mutans by I. Kubo et al., J. Agric. Food 
Chem., 41, 2447 (1993). This bacterium is responsible for causing dental 
caries. Carvone, the chief component of spearmint oil, was reported to 
exhibit antifungal activity by V. Moleyar et al., Food Microbiol., 3, 331 
(1986). Kubo et al., J. Natural Products, 57, 9 (1994) subsequently 
reported that a number of cyclic and acyclic terpene alcohols, including 
geranylacetol, farnesol and farnesyl acetol, exhibited activity against 
Pr. acnes, the bacterium responsible for acne. However, the linear ketone 
derived from farnesylacetol, farnesylacetone, was found to be inactive. 
While some of these natural products may be potent enough for practical 
use, the synthesis or extraction of highly branched cyclic or alicyclic 
terpenes can be complex. Furthermore, terpenes such as ionone, a component 
of cedar oil, can cause allergic skin reactions. Nonetheless, essential 
oils and other phytochemicals are by definition biodegradable and 
renewable. Therefore, a continuing need exists for compounds of natural 
origin which exhibit useful levels of biocidal activity. 
SUMMARY OF THE INVENTION 
The present invention provides a method to inhibit the growth of 
microorganisms, particularly microorganisms that are responsible for 
mammalian skin pathologies, comprising contacting the microorganisms with 
an effective growth-inhibiting amount of a 3-alken-2-one of the general 
formula (I): 
##STR1## 
wherein n is 6-16 and X.dbd.Y.dbd.H or X and Y together are a covalent 
bond. Preferably n is 5-11 and X.dbd.Y.dbd.H, or n is 6-10 and X and Y 
together are a covalent bond. Preferably the 3,4-double bond is in the E- 
or trans-configuration. 
Thus, the present invention also provides a composition adapted for topical 
application to the skin comprising an effective antimicrobial amount of at 
least one compound of formula (I), in combination with a dermatologically 
acceptable carrier. Preferred compositions in accord with the present 
application are therapeutic compositions adapted for topical application, 
as to the skin of a mammal afflicted with, or at risk of affliction with, 
a pathology associated with a microorganism such as a bacterium, a yeast 
or a fungus. Novel compounds of formula (I) are also within the scope of 
the invention, including 3-hexadecen-2-one. 
The term "skin" as used herein is to be construed broadly, to include the 
epidermis, the lips, the scalp, the epithelium of the eye, the surfaces of 
body cavities, including the mouth, ear, nose, vagina, anus and the like, 
and the surfaces of wounds or lesions in the skin. The term 
"antimicrobial" or "inhibit," as used with respect to the growth of 
microorganisms, is defined to encompass both complete inhibition (killing) 
of the microbes, as well as significant inhibition in growth or 
sporulation, as determined by the assays described herein, or by other 
standard assays, such as those disclosed by A. M. Janssen et al., Planta 
medica, 53, 395 (1987). Thus, the term "antimicrobial" encompasses the use 
of the present compounds in deodorant compositions, to control body odor, 
as well as in therapeutic compositions. All percentages are by weight 
unless otherwise noted.

DETAILED DESCRIPTION OF THE INVENTION 
A. Preparation 
The 3-alken-2-ones of the present invention which are not commercially 
available, or which are novel compounds can be prepared by a number of 
methods available to the art. For example, 3-alken-2-ones of general 
formula RCH.dbd.CH-C(O)-CH.sub.3 can generally be prepared by the crossed 
aldol condensation of acetone and the alkanal (RCHO), followed by the 
acid-catalyzed elimination of water from the resultant hydroxy ketone. 
See, for example, B. V. Burger et al., J. Chem. Ecol., 16, 397 (1990) 
(3-dodec-2-one) and G. Tishenko et al., J. Gen. Chem. USSR, 33, 134 (1963) 
(3-nonen-2-one). Alternatively, they can be prepared by the Wittig or 
Wittig-Horner reaction. 
Y. -Z. Huang et al., Synth. Commun., 19, 501 (1989) have also reported a 
general synthesis of 2-alken-2-ones (trans-RCH.dbd.CHC(O)CH.sub.3) by the 
reaction of the aldehyde (RCHO) with .alpha.-bromoacetone in the presence 
of tri-n-butylstibine for 1-16 hr at 25.degree.-50.degree. C., and 
prepared compounds wherein R is n-C.sub.4 H.sub.9, n-C.sub.8 H.sub.17 or 
n-C.sub.11 H.sub.23. The 3-alken-2-one wherein R is n-C.sub.13 H.sub.26 
has been reported by R. Kazlauskas et al., Aust. J. Chem., 33, 2097 
(1980). 
The 3-alkene-2-one wherein R is C.sub.7 H.sub.15 has been reported by H. A. 
Palma-Fleming et al., Phytochem., 22, 1503 (1983). The 3-aken-2-one 
wherein R is C.sub.9 H.sub.19, was prepared by A. A. Croteau et al., Tet. 
Letters, 24, 2481 (1983), who report a general synthesis of E/Z mixtures 
of 3-alken-2-ones by the condensation of lithiated .alpha.-silylketimine 
(Me.sub.3 Si-CHLi-C(.dbd.Nt-Bu)Me) with RCHO, followed by hydrolysis. 
Also, the preparation of (Z)-3-alken-2-ones by the condensation of alkenyl 
lithiocuprates with acetyl halides has been reported by N. Jabri et al., 
Tetrahedron, 42, 1369 (1986). The preparation of 3-tetradecen-2-one 
(R.dbd.C.sub.10 H.sub.21) has been reported by J. Kang et al., Bull. 
Korean Chem. Soc., 15, 306 (1994). 
B. Bioactivity 
The present compounds and compositions comprising them can be employed in a 
wide range of antimicrobial applications, including surface disinfecting, 
and for treating foods such as fruits and seeds. The present compounds are 
particularly useful to inhibit the growth of pathological microorganisms, 
such as bacteria, fungi and yeasts on the skin of humans and of animals 
such as household pets, farm animals and zoo animals. Such grampositive 
microorganisms include Propionibacterium acnes which is the primary 
pathogen which causes human acne vulgaris, and the streptocci and 
staphylococci which cause impetigo. Mycotic infections of animals and 
humans can also be treated, including tinea capitis, tinea cruris (jock 
itch), tinea corporis (ringworm), tinea pedis (athlete's foot) and tinea 
unguium. Fungi associated with such dermatophytosis include T. 
mentagrophytes, M. audevinii, T. rubrum, E. floccosum, M. pelineum and 
Candida albicans. 
The present compounds are also effective against fungi associated with 
infections of the membranes of body cavities. Such infections include 
thrush, vaginitis and paronychia. See R. T. Yousef et al., Mykosen, 21, 
190 (1978) and H. Gershon, J. Pharm. Sci., 68, 82 (1979). The present 
compounds can also be used in cosmetic and skin-cleansing compositions 
such as soaps, shampoos, deodorants, and skin softening lotions, where 
they can function as deodorants, i.e., to control odor-causing bacteria on 
the skin. The present compounds can also be employed in dentifrices, 
chewing gums, and mouthwashes to inhibit the growth of Streptococcus 
mutans, which is a causative agent for dental caries, and in shampoos, 
rinses, and other haircare products, to inhibit Pityrosporum ovale 
(dandruff, skin lesions in immune-suppressed subjects). Infections due to 
Staphylococcus aureus are also susceptible to these compounds. 
C. Compositions. 
Although in some instances, the present compounds may be administered in 
pure form, i.e., when they are liquids, it will generally be desirable to 
administer them to the skin as compositions or formulations, in 
combination with a dermatologically acceptable carrier, which may be a 
solid or a liquid. 
Useful solid carriers include finely divided solids such as talc, clay, 
microcrystalline cellulose, silica, alumina and the like. Useful liquid 
carriers include water, alcohols or glycols or water-alcohol/glycol 
blends, in which the present compounds can be dissolved or dispersed at 
effective levels, optionally with the aid of non-toxic surfactants. 
Adjuvants such as flavorings, fragrances and additional antimicrobial 
agents can be added to optimize the properties for a given use. The 
resultant liquid compositions can be applied from absorbent pads, used to 
impregnate bandages and other dressings, or sprayed onto the affected area 
using pump-type or aerosol sprayers. The liquid compositions can also be 
employed as eyedrops, mouth washes, douches, etc. Antibacterial 
presaturated wipes are disclosed by Anderson (U.S. Pat. No. 4,896,768). 
Thickeners such as synthetic polymers, fatty acids, fatty acid salts and 
esters, fatty alcohols, modified celluloses or modified mineral materials 
can also be employed with liquid carriers to form spreadable pastes, gels, 
ointments, soaps, and the like, for application directly to the skin of 
the user. 
The total concentration of one or more compounds of formula (I) in the 
present compositions can be varied widely, and will depend on factors such 
as the compatibility of the active ingredient(s) with the vehicle, the 
potency of the active ingredient(s) and the condition to be treated. 
Generally, the concentration of the compound(s) of formula (i) in a liquid 
composition, such as a lotion, will be from about 0.1-25 wt-%, preferably 
from about 0.5-10 wt-%. The concentration in a semi-solid or solid 
composition such as a gel or a powder will be about 0.1-5 wt-%, preferably 
about 0.5-2.5 wt-%. 
The present compounds of formula (I) are particularly useful to treat human 
or animal acne by topical application, as gels, ointments, lotions, soaps, 
and the like. For a further discussion of the pathology and etiology of 
acne, and of the formulation of aqueous cream and gel vehicles as carriers 
for other agents used to treat acne, see Klein et al. (U.S. Pat. No. 
4,692,329). The total dosage delivered will depend on the extent of the 
infected area to be treated, the severity of the infection and the number 
of applications, as determined by the subject's dermatologist, physician 
or veterinarian. 
The present invention will be further described by reference to the 
following detailed examples. 
EXAMPLE 1 
Synthesis of (E)-3-Alken-2-ones and (E)-3,13-Tetradecadien-2-one 
To 5.0 g of piperidine, 5.0 g of glacial acetic acid and. 250 mL of acetone 
at reflux in a 500 mL round-bottomed flask was added 0.10 mole of one of 
the following aldehydes (octanal, nonanal, decanal, undecanal, 
10-undecenal, dodecanal, tridecanal, or tetradecanal) in 50 mL of acetone 
dropwise over 0.5 hours. After addition, the solution was refluxed for an 
additional 5 hours. The acetone was removed in vacuo and the residue was 
placed in 50 mL of diethyl ether. The ether solution was washed with 
2.times.50 mL water, 2.times.50 mL 1M HCl and 2.times.50 mL saturated 
NaHCO.sub.3. The ether solution was dried with anhydrous CaCl.sub.2 and 
the ether was removed in vacuo. A pure sample of each compound was 
obtained by preparative gas chromatography. 
EXAMPLE 2 
Spectral Data for (E)-3-Alken-2-ones and (E)-3,13-Tetradecadien-2-one 
Mass spectra of the following compounds were recorded on a Hewlett-Packard 
gas chromatograph (Model 5890) fitted with a mass selective detector 
(Model 5970) using a 12 m cross-linked methyl silicone capillary column. 
The gas chromatograph was programmed so the oven temperature was kept at 
40.degree. C. for 4 minutes, then increased to a final temperature of 
250.degree. C. at a rate of 30.degree. C./min and kept at this temperature 
for four minutes. Mass spectral fragments below m/z=35 were not recorded. 
The mass selective detector was tuned using perfluorotributylamine and the 
internal computer tuning program. 
The .sup.1 H and .sup.13 C NMR spectra of the compounds were recorded at 
300 MHz and 75 MHz respectively on Bruker QE plus. Samples were dissolved 
in CDCl.sub.3, and chemical shifts are given in ppm relative to 
tetramethylsilane (TMS) at zero ppm using the solvent peak a 77.0 ppm as 
the internal standard. The synthetic 3-alken-2-ones and 
3,13-tetradecadien-2-one were shown to be the (E)-isomer by the .sup.1 
H-NMR coupling constant of 15.9 Hz for the olefinic protons. 
A. (E)-3-Undecen-2-one (1). 300 MHz .sup.1 H-NMR 
(CDCl.sub.3).delta.=6.78(dt,1H,J=15.9 Hz,6.9 Hz), 6.03(dt, 1H,J=15.9 
Hz,J=1.48 Hz), 2.21(s,3H), 2.19(quart,2H), 1.44(m,2H), 1.26(m,8H) and 
0.85(t,3H); 75 MHz .sup.13 C-NMR (CDCl.sub.3) .delta.=198.74, 148.68, 
131.29, 32.50, 31.75, 29.17, 29.08, 28.12, 26.82, 22.65, 14.09; and E1-MS 
m/z=97(7), 83(5), 81(6), 71(15), 69(18), 68(6),55(50). 43(100), 41(40) and 
39(19). 
B. (E)-3-Dodecen-2-one (2). 300 MHz .sup.1 H-NMR (CDCl.sub.3) 
.delta.=6.73(dt,1H,J=15.9 Hz,6.9 Hz), 5.99(dt,1H,J=15.9 Hz,J=1.48 Hz), 
2.18(s,32.15(quart,2H), 1.38(m,2H), 1.21(m, 10H) and 0.81(t,3H); 75 MHz 
.sup.13 C-NMR (CDCl.sub.3) .delta.=198.80, 148.72, 131.31, 32.53, 31.87, 
29.39, 29.23, 28.13, 26.84, 22.69, and 14.13; and E1-MS m/z=97(15), 
83(11), 82(9), 81(8), 71(25), 69(18), 55(50), 43(100), 41(37) and 36(18). 
C. (E)-3-Tridecen-2-one (3). 300 MHz .sup.1 H-NMR (CDCl.sub.3) 
.delta.=6.81(dt, 1H,J=15.9 Hz,6.9 Hz), 6.06(dt, 1H,J=15.9 Hz,J=1.48 Hz), 
2.24(s,3H), 2.22(quart,2H), 1.46(m,2H), 1.26(m, 12H) and 0.88(t,3H); 75 
MHz .sup.13 C-NMR (CDCl.sub.3) .delta.=198.80, 148.69, 131.24, 32.47, 
31.85, 29.46, 29.37, 29.27, 29.17, 28.07, 26.79, 22.65, and 14.09; E1-MS 
m/z=196(M.sup.+,2), 181(8), 97(31), 96(14), 83(22), 81(20), 71(34), 
69(31), 55(65), 43(100), 41(44); and FT-IR (neat) 2925, 2854, 1700, 1677, 
1628, 1467, 1360, 1253, 1189 and 980 cm.sup.-1. 
D. (E)-3-Tetradecen-2-one (4). 300 MHz .sup.1 H-NMR (CDCl.sub.3) 
.delta.=6.79(dt,1H,J=15.9 Hz,6.9 Hz), 6.05(dt,1H,J=15.9 Hz,J=1.48 Hz), 
2.23(s,3H), 2.21(quart,2H), 1.45(m,2H), 1.26(m, 14H) and 0.87(t,3H); 75 
MHz .sup.13 C-NMR (CDCl.sub.3) .delta.=198.79, 148.71, 131.31, 32.53, 
31.94, 29.62, 29.57, 29.43, 29.36, 29.23, 28.13, 26.84, 22.72, and 14.15; 
E1-MS m/z=97(21), 84(9), 83(8), 81(12), 71(30), 69(18), 55(50), 43(100), 
41(50) and 39(18). 
E. (E)-3,13-Tetradecadien-2-one (5). 300 MHz .sup.1 H-NMR (CDCl.sub.3) 
.delta.=6.80(dt,1H,J=15.9 Hz,6.9 Hz), 6.06(dt,1H,J=15.9 Hz,J=1.48 Hz), 
5.80(m,1H), 4.95(m,2H), 2.24(s,3H), 2.22(quart,2H), 2.03(quart,2H), 
1.46(m,2H) and 1.28(m, 10H); 75 MHz .sup.13 C-NMR (CDCl.sub.3) 
.delta.=198.83, 148.71,139.18, 131.32, 114.20, 33.83, 32.52, 29.38, 29.21, 
29.12, 28.94, 28.13, 26.87; E1-MS m/z=97(20), 95(14), 81(21), 71(19), 
69(17), 67(23), 55(59), 43(100), 41(71) and 39(35). 
F (E)-3-Pentadecen-2-one (6). 300 MHz .sup.1 H-NMR (CDCl.sub.3) 
.delta.=6.80(dt, 1H,J=15.9 Hz,6.9 Hz), 6.05(dt, 1H,J=15.9 Hz,J=1.48Hz), 
2.23(s,3H), 2.21(quart,2H), 1.46(m,2H), 1.26(m, 16H) and 0.88(t,3H); 75 
MHz .sup.13 C-NMR (CDCl.sub.3) .delta.=198.79, 148.71, 131.31, 32.53, 
31.96, 29.66, 29.57, 29.44, 29.38, 29.33, 29.24, 28.14, 26.85, 22.73, and 
14.16; E1-MS m/z=97(18), 84(10), 81(11), 71(28), 69(16), 68(10), 67(10), 
55(46), 43(100), and 41(40). 
G. (E)-3-Hexadecen-2-one (7). 300 MHz .sup.1 H-NMR (CDCl.sub.3) 
.delta.=6.80(dt,1H,J=15.9 Hz,6.9 Hz), 6.06(dt,1H,J=15.9 Hz,J=1.48 Hz), 
2.24(s,3H), 2.22(quart,2H), 1.47(m,2H), 1.26(m,18H) and 0.88(t,3H); 75 MHz 
.sup.13 C-NMR (CDCl.sub.3) .delta.=198.83, 148.74, 131.31, 32.54, 31.97, 
29.71, 29.68, 29.58, 29.54, 29.44, 29.41, 29.25, 28.15, 26.85, 22.74, and 
14.17; E1-MS m/z=97(18), 84(8), 83(8), 82(8), 81(9), 71(30), 69(15), 
55(42), 43(100), and 41(50). 
H. (E)-3-Heptadecen-2-one (8). 300 MHz .sup.1 H-NMR (CDCl.sub.3) 
.delta.=6.80(dt,1H,J=15.9 Hz,6.9 Hz), 6.07(dt,1H,J=15.9 Hz,J=1.48 Hz), 
2.24(s,3H), 2.22(quart,2H), 1.47(m,2H), 1.26(m,20H) and 0.88(t,3H); 75 MHz 
.sup.13 C-NMR (CDCl.sub.3) .delta.=198.83, 148.74, 131.32, 32.54, 31.97, 
29.70, 29.58, 29.44, 29.41, 29.34, 29.25, 28.15, 26.87, 22.74, and 14.18; 
and E1-MS m/z=252 (M+, 3), 97(19), 84(8), 83(10), 81(11), 71(28), 69(14), 
55(39), 43(100), and 41(50). 
EXAMPLE 3 
Bioassays 
The microorganisms tested were from the American Type Culture Collection 
(Rockville, Md.). They are Bacillus subtilis ATCC 9372, Brevibacterium 
ammoniagenes ATCC 6872, Staphylococcus aureus ATCC 12598, Streptococus 
mutans ATCC 25175, Propionibacterium acnes ATCC 11827, Pseudimonas 
aeruginosa ATCC 10145, Enterobacter aerogenes ATCC 13048, Eschericia coli 
ATCC 9637, Proteus vulgaris ATCC 133315, Saccharomyces cerevisiae ATCC 
7754, Candida utilis ATCC 9226, Pityrosporum ovale ATCC 14521, Penicillium 
chrysogenum ATCC 10106 and Trichophyton mentagrophytes ATCC 18748. 
The bacterial culture media except for S. mutans was 0.8% nutrient broth 
(BBL), 0.5% yeast Extract (Difco) and 0.1% glucose (NYG broth). S. mutans 
was cultured in 3.7% brain heart infixsion broth (Difco). All fungi, 
except P. ovale and T. mentagrophytes were cultured in a 2.5% malt extract 
broth (BBL). P. ovale was cultured in 1% bactopeptone (Difco), 0.5% yeast 
extract, 1% glucose and 0.1% corn oil. For T. mentagrophytes the culture 
media was 1% bactopeptone and 4% glucose. 
Freeze dried samples were prepared for testing as follows. B. subtilis, S. 
cerevisiae, C. utilis, and P. ovale, were shake-cultured for two days at 
30.degree. C. P. chrysogenum and T. mentagrophytes were shake-cultured for 
5 days at 30.degree. C. B. ammoniagenes and E. aerogenes were stationarily 
cultured at 30.degree. C. S. aureus, S. mutans, P. acnes, P. aeruginosa, 
E. coli and P. vulgaris were stationarily cultured at 37.degree. C. 
The minimum inhibitory concentration (MIC) of the 3-alken-2-ones (compounds 
1-4, 6-8) and 3,13-tetradecadien-2-one (compound 5) was performed using a 
two-fold serial broth dilution. Each test compound was dissolved in DMF 
and 30 .mu.L of this sample was dissolved in 3 mL of the applicable 
medium. A 30 .mu.L sample of the previously described culture of each 
microorganism was added to the various medium solutions. After two days, 
the cultures of B. subtilis, S. cerevisiae, C. utilis B. ammoniagenes, E. 
aerogenes, S. aureus, S. mutans, P. acnes, P. aeruginosa, E. coli and P. 
vulgaris were examined for turbidity (OD at 660 nm). The fungi, P. ovale, 
P. chrysogenum and T. mentagrophytes, were examined visually for growth at 
3 days (P. ovale) and 5 days (P. chrysogenum and T. mentagrophytes). The 
MIC was determined as the lowest concentration for each compound that no 
growth was observed. The highest concentration used in these tests was 800 
.mu.g/mL. 
TABLE 1 
__________________________________________________________________________ 
MIC of (E)-3-Alken-2-ones and (E)-3,13-tetradecadien-2-one (.mu.g/mL) 
Compound Tested 
Organism 1 2 3 4 5 6 7 8 
__________________________________________________________________________ 
Bacillus subtilis ATCC 9372 
100 100 100 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
Brevibacterium ammoniagenes ATCC 6872 
200 100 100 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
Staphylococcus aureus ATCC 12598 
200 100 50 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
Streptococus mutans ATCC 25175 
100 50 25 
25 
25 
200 
400 
800 
Propionibacterium acnes ATCC 11827 
50 25 12.5 
12.5 
12.5 
6.25 
3.13 
3.13 
Pseudimonas aeruginosa ATCC 10145 
&gt;800 &gt;800 &gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
Enterobacter aerogenes ATCC 13048 
&gt;800 &gt;800 &gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
Eschericia coli ATCC 9637 
&gt;800 &gt;800 &gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
Proteus vulgaris ATCC 133315 
50 50 800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
Saccharomyces cerevisiae ATCC 7754 
800 800 &gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
Candia utilis ATCC 9226 
50 400 &gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
&gt;800 
Pityrosporum ovale ATCC 14521 
100 100 100 
100 
200 
400 
&gt;800 
&gt;800 
Penicillium chrysogenum ATCC 10106 
100 100 800 
800 
800 
&gt;800 
&gt;800 
&gt;800 
Trichophyton mentagrophytes ATCC 18748 
100 100 25 
12.5 
12.5 
800 
&gt;800 
&gt;800 
__________________________________________________________________________ 
As demonstrated by the data summarized in Table 1, the greatest activity 
observed with compounds 1-8 occurred against P. acnes, the primary 
pathogen responsible for causing human acne. Compounds 1-5 also exhibited 
substantial activity against T. mentagrophytes, the causative agent of 
athlete's foot and compounds 1-7 inhibited Streptococcus mutans (dental 
caries). Compounds 1-6 also exhibited somewhat lesser activity against P. 
ovale (dandruff) and compounds (1)-(3) were active against S. aureus and 
Proteus vulgaris. Specifically, (E)-3-tridecen-2-one (3), showed activity 
against all of the grampositive bacteria (B. subtilis, B. ammoniagenes, S. 
aureus, S. mutans, and P. acnes) in the test. It was most active against 
P. acnes, having a minimum inhibitory concentration (MIC) of 12.5 
.mu.g/mL. This compound was not active against the gram-negative bacteria, 
P. aeruginosa, E. aerogenes and E. coli. Activity against yeast was mixed, 
no activity was seen against S. cerevisiae and C. utilis, although P. 
ovale showed moderate inhibition. Weak activity was seen with fungi P. 
chrysogenum, while the fungi T. mentagrophytes had a MIC of 25 .mu.g/mL. 
(E)-3-tetradecen-2-one (4), showed activity against some gram-positive 
bacteria (S. mutans, and P. acnes) in the test. It was most active with P. 
acnes having a minimum inhibitory concentration (MIC) of 12.5 .mu.g/mL. 
This compound was not active against the gram-negative bacteria, P. 
aeruginosa, E. aerogenes and E. coli. Activity against yeast was mixed, no 
activity was seen against S. cerevisiae and C. utilis, although P. ovale 
showed moderate inhibition. Weak activity was seen with fungi P. 
chrysogenum, while the fungi T. mentagrophytes had a MIC of 12.5 .mu.g/mL. 
The synthetic products, (E)-3-hexadecen-2-one (7) and 
(E)-3-heptadecen-2-one (8), were inactive to all of the bacteria and fungi 
in the test, except S. mutans and P. acnes. With S. mutans (7) was weakly 
active, but (7) and (8) exhibited strong activity (3.13 .mu.g/mL) against 
P. acnes. 
EXAMPLE 4 
A powder composition may be prepared having the following formulation: 
______________________________________ 
Per Canister 
______________________________________ 
Compound 4 1.0 g 
Talc 99 g 
______________________________________ 
EXAMPLE 5 
A lotion composition may be prepared having the following formulation: 
______________________________________ 
Per Canister 
______________________________________ 
Compound 7 1.0 g 
Cetyl Alcohol 25 g 
Glyceryl Stearate 25 g 
Glycerol 20 g 
Water 10 g 
Stearyl Alcohol 10 g 
______________________________________ 
EXAMPLE 6 
A lotion composition may be prepared having the following formulation: 
______________________________________ 
Per Canister 
______________________________________ 
Compound 7 0.5 g 
Compound 4 0.5 g 
Cetyl Alcohol 25 g 
Glyceryl Stearate 25 g 
Glycerol 20 g 
Water 10 g 
Stearyl Alcohol 10 g 
______________________________________ 
Other examples of useful dermatological compositions which can be used to 
deliver the compounds of claim 1 to the skin are disclosed in Jacquet et 
al. (U.S. Pat. No. 4,608,392), Geria (U.S. Pat. No. 4,992,478), Smith et 
al. (U.S. Pat. No. 4,559,157) and Wortzman (U.S. Pat. No. 4,820,508). 
All publications and patents are incorporated by reference herein, as 
though individually incorporated by reference. The invention has been 
described with reference to various specific and preferred embodiments and 
techniques. However, it should be understood that many variations and 
modifications may be made while remaining within the spirit and scope of 
the invention.