Abstract
A 17-membered macrocyclolipopeptide, named dysoxylactam A (1) comprising an unprecedented branched C19 fatty acid and an l-valine, was isolated from the plants of Dysoxylum hongkongense. The challenging relative configuration of 1 was established by means of residual dipolar coupling-based NMR analysis. The absolute configuration of 1 was determined by single-crystal X-ray diffraction on its p-bromobenzoate derivative (2). Compound 1 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 28.4 to 1039.7 at the noncytotoxic concentration of 10 μM. The mode-of-action study of 1 revealed that it inhibited the function of P-glycoprotein (P-gp), a key mediator in multidrug resistance.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / isolation & purification
-
Antineoplastic Agents / pharmacology*
-
Cell Line, Tumor
-
Drug Resistance, Multiple / drug effects*
-
Drug Resistance, Neoplasm / drug effects*
-
Drug Screening Assays, Antitumor
-
Humans
-
Lipopeptides / chemical synthesis
-
Lipopeptides / chemistry
-
Lipopeptides / isolation & purification
-
Lipopeptides / pharmacology*
-
Meliaceae / chemistry
-
Peptides, Cyclic / chemical synthesis
-
Peptides, Cyclic / isolation & purification
-
Peptides, Cyclic / pharmacology*
Substances
-
ATP Binding Cassette Transporter, Subfamily B, Member 1
-
Antineoplastic Agents
-
Lipopeptides
-
Peptides, Cyclic
-
dysoxylactam A