Antimycobacterial metabolites from Plectranthus: royleanone derivatives against Mycobacterium tuberculosis strains.
The antimycobacterial activities of eight diterpenes, 1-8, isolated previously from Plectranthus and eleven esters, 9-19, of 7alpha-acetoxy-6beta,12-dihydroxyabieta-8,12-diene-11,14-dione (5) were evaluated against the MTB strains H(37)Rv and MDR. Only diterpenoids with a quinone framework revealed anti-MTB activity. Abietane 5 and its 6,12-dibenzoyl, 12-methoxybenzoyl, 12-chlorobenzoyl, and 12-nitrobenzoyl esters, 9, 11, 12, and 13, respectively, showed potent activities against the MDR strain with MIC values between 3.12 and 0.39 microg/ml. Cytotoxic activities towards 3T3 and Vero cells were also evaluated. Compound 11, with the best selectivity index, may be a suitable lead for further chemical modifications. The complete structural elucidation of the new esters, 9-14, 16, 18, and 19, as well as the NMR data of known derivatives 15 and 17 are reported.
Rijo
Patrícia
P
Faculdade de Farmácia da Universidade de Lisboa, iMed.UL, Av. Prof. Gama Pinto, PT-1649-003 Lisboa.
Simões
M Fátima
MF
Francisco
A Paula
AP
Rojas
Rosario
R
Gilman
Robert H
RH
Vaisberg
Abraham J
AJ
Rodríguez
Benjamín
B
Moiteiro
Cristina
C
D016475:3T3 Cells; D045784:Abietanes / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D002522:Chlorocebus aethiops; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D031346:Plectranthus / Q000737:chemistry / Q000378:metabolism*; D014709:Vero Cells
D045784:Abietanes; D000900:Anti-Bacterial Agents; C103399:royleanone