Synthesis and evaluation of (S,S)-N,N'-bis-[3-(2,2',6,6'-tetramethylbenzhydryloxy)-2-hydroxy-propyl]-ethylenediamine (S2824) analogs with anti-tuberculosis activity.
In order to identify new and potent candidate drugs to treat tuberculosis, a library of compounds was screened, and (S,S)-N,N'-bis-[3-(2,2',6,6'-tetramethylbenzhydryloxy)-2-hydroxy-propyl]-ethylenediamine (S2824) was identified as a hit in the screen. This research discusses our efforts to synthesize and test 30 analogs of this hit for activity against Mycobacterium tuberculosis. Two compounds with homopiperazine ring possess high in vitro activity against drug sensitive and resistant M. tuberculosis with MICs 0.78-3.13 microg/mL (or 1.22-4.88 microM).
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
Xuelian
X
Zhang
Yanwei
Y
Hu
Shudan
S
Chen
Rusong
R
Luo
Jun
J
Yue
Ying
Y
Zhang
Wenhu
W
Duan
Honghai
H
Wang
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D024881:Drug Resistance, Bacterial; D005029:Ethylenediamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D014376:Tuberculosis / Q000188:drug therapy*
D000995:Antitubercular Agents; D001381:Azepines; D001559:Benzhydryl Compounds; D005029:Ethylenediamines; C546149:N,N'-bis(3-(2,2',6,6'-tetramethylbenzhydryloxy)-2-hydroxypropyl)ethylenediamine; C546150:S 282429; C546151:S 282430