Bioorganic and Medicinal Chemistry p. 6501 - 6508 (2008)
Update date:2022-07-30
Topics:
Turos, Edward
Revell, Kevin D.
Ramaraju, Praveen
Gergeres, Danielle A.
Greenhalgh, Kerriann
Young, Ashley
Sathyanarayan, Nalini
Dickey, Sonja
Lim, Daniel
Alhamadsheh, Mamoun M.
Reynolds, Kevin
This study describes the antibacterial properties of synthetically produced mixed aryl-alkyl disulfide compounds as a means to control the growth of Staphylococcus aureus and Bacillus anthracis. Some of these compounds exerted strong in vitro bioactivity. Our results indicate that among the 12 different aryl substituents examined, nitrophenyl derivatives provide the strongest antibiotic activities. This may be the result of electronic activation of the arylthio moiety as a leaving group for nucleophilic attack on the disulfide bond. Small alkyl residues on the other sulfur provide the best activity as well, which for different bacteria appears to be somewhat dependent on the nature of the alkyl moiety. The mechanism of action of these lipophilic disulfides is likely similar to that of previously reported N-thiolated β-lactams, which have been shown to produce alkyl-CoA disulfides through a thiol-disulfide exchange within the cytoplasm, ultimately inhibiting type II fatty acid synthesis. However, the mixed alkyl-CoA disulfides themselves show no antibacterial activity, presumably due to the inability of the highly polar compounds to cross the bacterial cell membrane. These structurally simple disulfides have been found to inhibit β-ketoacyl-acyl carrier protein synthase III, or FabH, a key enzyme in type II fatty acid biosynthesis, and thus may serve as new leads to the development of effective antibacterials for MRSA and anthrax infections.
View MoreMeryer (Shanghai) Chemical Technology Co., Ltd.
website:http://www.meryer.com/cn/index/
Contact:+86-755-86170518
Address:Minhang,Shanghai, China
Chengdu Pukang Biotechnology Co., Ltd
website:http://www.pu-kang.com
Contact:86-028-63976226
Address:No. 868 Xiwang Road,Xinjin county,Chengdu city, China
Suzhou HeChuang Chemical Co.,Ltd.
Contact:+86-512-88800520
Address:No.9 Guanchao Rd,Changshu Advanced Materials Industy Park
Changzhou Hopschain Chemical Co.,Ltd
website:http://www.hopschem.cn/products.html
Contact:86-519-85528066
Address:Room 710, Unit A, Xingbei Development Mansion, Tongjiang Road, Changzhou City,213000, China
website:http://www.afinechem.com
Contact:+86-571-85134551
Address:No. 206 Zhen Hua Road, Hangzhou 310030, Zhejiang, China
Doi:10.1002/jhet.5570220549
(1985)Doi:10.1016/j.jorganchem.2008.08.038
(2008)Doi:10.1016/S0040-4039(00)99338-9
(1989)Doi:10.1021/jo01345a001
(1966)Doi:10.1139/v86-204
(1986)Doi:10.1021/jo801135j
(2008)