Biocatalytic and semisynthetic optimization of the anti-invasive tobacco (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol.
Tobacco cembranoids were reported to inhibit tumorigenesis. Biocatalysis of (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) using the symbiotic Bacillus sp. NC5, Bacillus sp. NK8, and Bacillus sp. NK7, isolated from the Red Sea sponge Negombata magnifica, afforded two new and four known hydroxylated metabolites 3-8. The use of symbiotic marine bacteria as biocatalysts for bioactive natural product scaffolds is very rare. Cembranoid 1 carbamate analogs 9-11 were prepared by its reaction with corresponding isocyanates. Cembranoid 1 and its bioconversion and carabamate products show anti-invasive activity against the human highly metastatic prostate PC-3M cancer cell line at 10-50 nM doses in Matrigel assay.
El Sayed
Khalid A
KA
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Monroe, LA 71209, USA. elsayed@ulm.edu
Laphookhieo
Surat
S
Baraka
Hany N
HN
Yousaf
Muhammad
M
Hebert
Anne
A
Bagaley
Danielle
D
Rainey
Frederick A
FA
Muralidharan
A
A
Thomas
Shibu
S
Shah
Girish V
GV
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001407:Bacillus / Q000378:metabolism*; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D011161:Porifera / Q000382:microbiology; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014026:Nicotiana / Q000737:chemistry
D000970:Antineoplastic Agents; D004224:Diterpenes