Semisynthetic and biotransformation studies of (1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol.
Tobacco-derived (1 S,2 E,4 S,6 R,7 E,11 E)-2,7,11-cembratriene-4,6-diol (1) and (1 S,2 E,4 R,6 R,7 E,11 E)-2,7,11-cembratriene-4,6-diol (2) were first shown to display potential antitumor-promoting activity in the mid-1980s. However, very little is currently understood regarding the structural activity relationships of tobacco cembranoids. The aim of this present study was to explore antiproliferative activity of various derivatives of (1 S,2 E,4 S,6 R,7 E,11 E)-2,7,11-cembratriene-4,6-diol (1) using semisynthetic and biotransformation approaches. Derivatives of 1 include esterified, oxidized, halogenated, and nitrogen- and sulfur-containing compounds (3-17). Biotransformation of 1 using Mucor ramannianus ATCC 9628 and Cunninghamella elegans ATCC 7929 afforded the known 10 S,11 S-epoxy analogue of 1 (4) as the main metabolite. Biotransformation of the 6-O-acetyl analogue (3) using the marine symbiotic Bacillus megaterium strain MO31 afforded (1 S,2 E,4 S,6 R,7 E,11 E,10 R)-2,7,11-cembratriene-4,6,10-triol (18). (1 S,2 E,4 S,6 R,7 E,11 E,13 R)-2,7,11-Cembratriene-4,6,13-triol-6-O-acetate (6), (1 S,2 E,4 S,6 R,7 E,11 E,13 S)-2,7,11-cembratriene-4,6,13-triol-6-O-acetate (7), the rearranged alpha-ketol (1 S,2 E,4 S,7 Z,11 E)-2,7,11-cembratrien-4-ol-6-one (11), and the secocembranoid 12 showed antiproliferative activity against highly malignant +SA mammary epithelial cells with an IC50 range of 15-30 microM.
El Sayed
Khalid A
KA
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe 71209, USA. elsayed@ulm.edu
Laphookhieo
Surat
S
Yousaf
Muhammad
M
Prestridge
Justin A
JA
Shirode
Amit B
AB
Wali
Vikram B
VB
Sylvester
Paul W
PW
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D001410:Bacillus megaterium / Q000378:metabolism; D001711:Biotransformation; D020093:Cunninghamella / Q000378:metabolism; D004224:Diterpenes / Q000138:chemical synthesis / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D009089:Mucor / Q000378:metabolism; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D013237:Stereoisomerism; D014026:Nicotiana / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; C046139:2,7,11-cembratriene-4,6-diol