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Planta Med 2011; 77(5): 467-476
DOI: 10.1055/s-0030-1250478
Natural Product Chemistry
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Bioactive Natural, Biocatalytic, and Semisynthetic Tobacco Cembranoids

Hany N. Baraka1 , 2 , Mohammad A. Khanfar1 , John C. Williams1 , Emad M. El-Giar3 , Khalid A. El Sayed1
  • 1Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana, USA
  • 2Current address: Department of Pharmacognosy, College of Pharmacy, Mansoura University, Mansoura, Egypt
  • 3Department of Chemistry, University of Louisiana at Monroe, Monroe, Louisiana, USA
Further Information

Publication History

received July 10, 2010 revised Sept. 19, 2010

accepted October 5, 2010

Publication Date:
03 November 2010 (online)

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Abstract

The two major Nicotiana tabacum tobacco cembranoids, (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) and its C-4 epimer, exhibit a wide range of interesting biological activities. Although the tumorigenesis inhibition activity of tobacco cembranoids have been known since the mid 1980′s, only a limited number of investigations have targeted their optimization and structure-activity relationship. This study reports the isolation of the new (1S,2E,4S,6E,8S,11E)-2,6,11-cembratriene-8-O-methyl-4,8-diol (3) and the known (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4-O-methyl-4,6-diol (2) from fresh N. tabacum leaves. Cembranoid 2 showed good anti-migratory activity against prostate cancer cell lines, and was therefore subjected to microbial transformation and semisynthetic optimization studies. Biotransformation of 2 using the fungal strains Cunninghamella NRRL 5695 and Mucor ramannianus ATCC 9628 afforded new (4 and 5) and known (6 and 7) metabolites. Semisynthetic esterification, oxidation, epoxidation, and reaction with Lawesson's reagent afforded the new products 8–14. Cembranoid 2 and its epoxidation product 9 showed potent anti-migratory activities against the highly metastatic human prostate cancer cell lines PC-3M-CT+ (spheroid disaggregation assay) and PC-3 (wound-healing assay).

Key words

anti‐migratory - microbial transformation - Nicotiana tabacum - Solanaceae - prostate cancer - spheroid disaggregation - wound‐healing

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Dr. Khalid A. El Sayed

Department of Basic Pharmaceutical Sciences
College of Pharmacy
University of Louisiana at Monroe

1800 Bienville Drive

Monroe, LA 71201

USA

Phone: +1 31 83 42 17 25

Fax: +1 31 83 42 17 37

Email: elsayed@ulm.edu

    www.thieme-connect.de/ejournals/toc/plantamedica