Relationship Between the Structures of Fatty Acid Amide Derivatives and Their Antimicrobial Activities

Abstract

The structure-activity relationships of derivatives of the antibiotic cerulenin were investigated by chemically modifying dodecanoic acid, its skeletal backbone. The dimethylamide derivatives were active against both gram-positive and -negative bacteria, and fungi. Among the compounds having modified groups at positions C2 and C4, the most active were those with a carbonyl group at C4 and a double bond at C2. The dimethylamide and pyrrolidine amide derivatives of this structure type were the most active. Activity against bacteria and yeast increased with the number of carbon atoms in the skeleton, with the maximum activity being observed at C=12. No significant differences in activity against fungi were observed with change in chain length.

Enzymatic Synthesis of Fatty Amides fromPalm Olein

“…They have attracted much attention due to due to their biological activities 1) and potential industrial applications such as surfactants, lubricants, cosmetics, detergents and anti-blocking agents in the plastics processing industry [2][3][4] . Fatty amides are produced in thousands of metric tons a year from fatty acids by reaction with anhydrous ammonia at approximately 200 and 345-690 kPa 5) .…”

Synthesis and Characterization of N,N'-Carbonyl Difatty Amides from Palm Oil

“…Fatty amides have attracted much attention due to their activities against bacteria, yeasts, and molds 1) and industrial applications as surfactants, lubricants, cosmetics, shampoos, detergents, antifoams and other utilizations 2,3) . There are several reports on the synthesis of fatty amides from fatty acids or their esters with various amine compounds either under high temperature and pressure 4,5) or by enzymatic synthesis [6][7][8] .…”

Mechanism of Action of CM-55, a Synthetic Analogue of the Antilipogenic Antibiotic Cerulenin

“…One of them, CM-55 (2,3-dodecenyl-4-oxodimethyl amide [ Fig. 1]), lacks an epoxide function but has an antimicrobial spectrum quite similar to that of cerulenin (11). These characteristics led us to investigate its mode of action compared with that of cerulenin.…”

“…As has been presented by D'Agnolo et al (2), the epoxide ring at the 2-3 position of cerulenin is essential for the inhibition of ,Bketoacylacyl carrier protein synthetase activity, but the two double bonds at the 7 and 10 positions are not necessarily essential, though they are important, for inhibitory activity. The integrity of the epoxide is also required for antimicrobial activity (11). Therefore, the rapid inactivation of cerulenin was assumed because of the degradation of the epoxide ring by mammalian epoxidase.…”

“…Cerulenin was obtained from the culture broth of C. caerulens KF-140 by the methods previously reported (6). CM-55 was synthesized as previously reported (11). Fresh removed and the cells were trapped on a membrane filter, immediately followed by washing with 10 ml of ice-cold 0.01 M tris(hydroxymethyl)aminomethanehydrochloride buffer (pH 7.0) containing 0.15 M NaCl and 0.5 mM MgCl,.…”