title: Biocatalytic and semisynthetic optimization of the anti-invasive tobacco (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol.
abstract: 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.
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Monroe, LA 71209, USA. elsayed@ulm.edu
authors.forename: Khalid A
authors.initials: KA
authors.lastname: El Sayed
authors.forename: Surat
authors.initials: S
authors.lastname: Laphookhieo
authors.forename: Hany N
authors.initials: HN
authors.lastname: Baraka
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yousaf
authors.forename: Anne
authors.initials: A
authors.lastname: Hebert
authors.forename: Danielle
authors.initials: D
authors.lastname: Bagaley
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Rainey
authors.forename: A
authors.initials: A
authors.lastname: Muralidharan
authors.forename: Shibu
authors.initials: S
authors.lastname: Thomas
authors.forename: Girish V
authors.initials: GV
authors.lastname: Shah
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes