Synthesis and antimicrobial activity of 3-alkoxyjatrorrhizine derivatives.
The compounds 3-ethoxy- ( 2), 3-butoxy- ( 3), 3-hexyloxy- ( 4), 3-octyloxy- ( 5), 3-decyloxy- ( 6) and 3-dodecyloxyjatrorrhizine chlorides ( 7) were synthesized and tested for their antimicrobial activity in vitro to evaluate structure-activity relationships. Substitution of the H with alkyl groups at C-3-OH led to significant changes in the antimicrobial activity. The antimicrobial activity of the substituted derivatives was 32 - 1000 times higher than that of jatorrhizine ( 1), which increased as the aliphatic chain was elongated and then decreased slightly when the alkyl chain exceeded eight carbon atoms. 3-Octyloxyjatrorrhizine ( 5) displayed the highest antimicrobial activity of all compounds. The LD (50) values of compounds 1 - 7 were more than 6000 mg/kg body weight, showing a low toxicity. The toxicities of compounds 2 - 7 were slightly lower than that of ( 1).
Wang
Li-jun
LJ
Chemistry Institute of Pharmaceutical resources, School of Pharmaceutical Science, Southwest University, Chongqing, P. R. China.
Ye
Xiao-li
XL
Li
Xue-gang
XG
Sun
Qing-lei
QL
Yu
Gang
G
Cao
Xiao-gang
XG
Liang
Yan-ting
YT
Zhang
Hua-san
HS
Zhou
Jia-zhou
JZ
D000890:Anti-Infective Agents / Q000032:analysis*; D001599:Berberine / Q000031:analogs & derivatives* / Q000032:analysis; D039323:Coptis / Q000737:chemistry; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D018675:Toxicity Tests
D000890:Anti-Infective Agents; D004365:Drugs, Chinese Herbal; C055785:jatrorrhizine; D001599:Berberine