Sapelenins G-J, acyclic triterpenoids with strong anti-inflammatory activities from the bark of the Cameroonian medicinal plant Entandrophragma cylindricum.
Four acyclic triterpene derivatives named sapelenins G-J (1-4), along with eight known compounds, sapelenins A-D, ekeberin D2 (5), (+)-catechin and epicatechin, and anderolide G, were isolated from the stem bark of the Cameroonian medicinal plant, Entandrophragma cylindricum Sprague, on the basis of bioassay-guided fractionation. Their structures were determined by means of high-resolution mass spectrometry and NMR spectroscopic data, as well as by comparison with the literature values of their analogs. The absolute configurations of the compounds (1-4) were assigned by the modified Mosher's method in conjunction with NOESY experiments and chemical modifications. The anti-inflammatory activities of the sapelenins were evaluated by assessing their ability to suppress or inhibit the secretion of cytokine interleukin-17 (IL-17) by human peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA). The cytotoxicity of these compounds on PMBCs was further assessed for correctly interpreting their anti-inflammatory responses. The tested compounds demonstrated moderate to significant anti-inflammatory activities by suppressing the secretion of IL-17 by PHA-stimulated human PBMCs. One of them, sapelenin G (1), showed high potency in suppressing the secretion of IL-17 by PBMCs comparable to reference cyclosporine A, without causing any cytotoxic effects (negligible), and deserves further considerations towards developing an effective anti-inflammatory drug.
Chair of Environmental Chemistry and Analytical Chemistry, Institute of Environmental Research-INFU of the Faculty of Chemistry, TU Dortmund, Otto-Hahn-Str. 6, D-44221 Dortmund, Germany.
Simeon Fogue
SF
Kouam
Souvik
S
Kusari
Marc
M
Lamshöft
Ostend Kamgue
OK
Tatuedom
Michael
M
Spiteller
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D029582:Meliaceae / Q000737:chemistry*; D008968:Molecular Conformation; D024301:Plant Bark / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020381:Interleukin-17; D010936:Plant Extracts; D014315:Triterpenes