Reversal of P-glycoprotein-mediated multidrug resistance by sipholane triterpenoids.
Nineteen triterpenoids, possessing four different skeletons, have been reported so far from the Red Sea sponge Siphonochalina siphonella. However, no biological activity of these compounds was ever reported. This study describes the isolation of two new triterpenoids, siphonellinol C (3) and sipholenol I (4), along with several known sipholane triterpenoids from the Red Sea sponge Callyspongia (=Siphonochalina) siphonella. Allylic oxidation of the major sipholane triterpenoids, sipholenol A (1) and sipholenone A (2), by selenium dioxide afforded four C-28-oxidized derivatives. Sipholane triterpenoids along with their semisynthetic derivatives were evaluated for their cytotoxicity and effect on reversing P-glycoprotein-mediated MDR to colchicine. Sipholenol A was found to be the most potent, and it increased the sensitivity of resistant KB-C2 cells by 16 times toward colchicine. This is the first report related to reversal of cancer chemotherapy resistance using these triterpenoids.
Jain
Sandeep
S
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana 71209, USA.
Laphookhieo
Surat
S
Shi
Zhi
Z
Fu
Li-Wu
LW
Akiyama
Shin-Ichi
S
Chen
Zhe-Sheng
ZS
Youssef
Diaa T A
DT
van Soest
Rob W M
RW
El Sayed
Khalid A
KA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019156:Indian Ocean; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014315:Triterpenes