Inhibition of cytokine production by hymenialdisine derivatives.
We describe herein the synthesis and biological activity of two indoloazepines that are structurally related to the marine sponge metabolite hymenialdisine. The natural product hymenialdisine was found to be a potent inhibitor of interleukin-2 (IC(50) = 2.4 microM) and tumor necrosis factor alpha (IC(50) = 1.4 microM) production. One of the hymenialdisine derived indoloazepines was found to also inhibit interleukin-2 (IC(50) = 3.5 microM) and tumor necrosis factor alpha (IC(50) = 8.2 microM) production.
Sharma
Vasudha
V
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Lansdell
Theresa A
TA
Jin
Guangyi
G
Tepe
Jetze J
JJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001381:Azepines; D016207:Cytokines; D007211:Indoles; D007376:Interleukin-2; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; C107079:hymenialdisine