New natural sesquiterpenes as modulators of daunomycin resistance in a multidrug-resistant Leishmania tropica line.
The effects produced by nine dihydro-beta-agarofuran sesquiterpenes isolated from Crossopetalum tonduzii (1-8) and Maytenus macrocarpa (9) (Celastraceae) on the reversion of the resistant phenotype on a multidrug-resistant Leishmania line and their binding to recombinant C-terminal nucleotide-binding domain of Leishmania P-glycoprotein-like transporter were studied. The structures of the new compounds (1-5) were elucidated by spectroscopic methods, including (1)H-(13)C heteronuclear correlation (HMQC), long-range correlation spectra with inversal detection (HMBC), ROESY experiments, and chemical correlations. The absolute configuration of one of them (1) was determined by CD studies. The structure-activity relationship is discussed.
Pérez-Victoria
J M
JM
Instituto de Parasitología y Biomedicina "López-Neyra", Consejo Superior de Investigaciones Científicas, Ventanilla, 11, 18001 Granada, Spain.
Tincusi
B M
BM
Jiménez
I A
IA
Bazzocchi
I L
IL
Gupta
M P
MP
Castanys
S
S
Gamarro
F
F
Ravelo
A G
AG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002942:Circular Dichroism; D003630:Daunorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D004926:Escherichia coli / Q000378:metabolism; D007895:Leishmania tropica / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D019685:Rosales / Q000737:chemistry*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
C400071:8-acetoxy-9-benzoyloxy-15(2)-methylbutyroyloxy-2-nicotynoyloxy-1,4,6-trihydroxydihydro-beta-agarofuran; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D012717:Sesquiterpenes; D014344:Trypanocidal Agents; D003630:Daunorubicin