Labdane activities

Biologically active secondary metabolites from fungi. 12. Oidiolactones A-F, labdane diterpene derivatives isolated from Oidiodendron truncata. John, M. Krohn, K. Florke, U. Aust, H-J. Draeger, S. Schulz, B. J. Nat. Prod. 1999, 62, 1218-1221. 

LABDANE -TYPE DITERPENES CHEMISTRY AND BIOLOGICAL ACTIVITY... 

The most important manoyl oxide derivative is forskolin (9), Fig. (7), (7p-acetoxy-8, 13-epoxy-la, 6p, 9a-trihydroxylabd-14-en-ll-one) [151-153]. It belongs to the labdane series of diterpenes and was isolated from the Indian herb Coleus forskohlii (Willd.) Briq. (Labiatae). Since ancient times it has been used in Hindu and Ayurvedic traditional medicine [154]. The plant Coleus forskohlii (Willd.) Briq. has been extensively studied, and from its extracted roots a group of diterpenoids, with the basic skeleton of 11-oxo-manoyl oxide, have been isolated. The main compound, forskolin, presented remarkable chemical and biological properties [155]. Analogues of forskolin were then prepared by semisynthesis [156] or obtained by microbial transformations [157]. New analogues, more soluble than forskolin have shown activities comparable to and even higher than forskolin [158]. 

A variety of biological activities have been associated with labdane diterpenes including antibacterial, antifungal, antiprotozoal, enzyme induction, anti-inflammatory modulation of immune cell functions, as well as cytotoxic and cytostatic effects against human leukemic cell lines. 

A series of other labdane diterpenes isolated from various sources have also been reported to exhibit antimicrobial activity. Aulacocarpinolide and aulacocarpines A and B, labdane diterpenes isolated from the Cameroonian spice Aframonum aulacocarpos (Zingiberaceae), exhibited weak antibacterial activity against B. subtilis and fungus Mucur miehei [166],... 

Labdanes of the series of gomojosidae, isolated from the leaves of Viburnum suspensum (Caprifoliaceae) exhibited antibacterial activity against E.coli, Aeromonas salmonishida and B. subtillis [102]. Cryptotrienolic and isocupressic acid isolated from the bark of Juniperus procera were found to exhibit weak antibacterial activity when tested against B. subtillis, S. aureus, Str. durans, E. faecilis, and Mycobacterium... 

In addition to the (antimicrobial, enzyme and endocrine related) properties mentioned above, it is interesting that many labdane type diterpenes also exhibit significant properties against cancer cells. A number of labdane type diterpenes tested exhibited remarkable antiproliferative and cytotoxic activities. Itokawa et al. [193] found that extracts from the rhizomes of Hedychium coronarium (Zingiberacae), cause growth inhibition of Chinese hamster V-79 cells and sarcoma 180 ascites in mice. Chemical analysis led to the isolation of 8 (17), 12 (E)-labdadiene-15, 16-dial along with four new coronarins (A-D). All of the compounds exhibited... 

As noted, the labdanes display a broad spectrum of biochemical and pharmacological activities, suggesting that they may significantly affect the function of the immune system and inflammatory cells. The labdanes may affect critical enzymes such as adenylate cyclase, protein kinases and phospholipase A2, which are intimately involved in signal transduction and cell activation processes. Much of the information on labdane-type diterpene effects has been provided by forskolin and mainly in in vitro systems. 

Uddin J, Ueda K, Siwu ERO, Kita M, Uemura D (2006) Cytotoxic Labdane Alkaloids from an Ascidian Lissoclinum sp. Isolation, Structure Elucidation, and Structure-Activity Relationship. Bioorg Med Chem 14 6954... 

An intramolecular 2-alkylation was also observed in a sulfonyl free radical induced addition-cyclization <95SL763>. A key intermediate in a new synthesis of pallescensin A (a biologically active labdane diterpene) was prepared by a cationic cyclization reaction with a furan <95SYN1141>. The sonochemical Barbier reaction was extended to carboxylate salts. 2-Furanylketones 10 can be obtained by sonication of a mixture of furan, lithium carboxylate, an alkylchloride, and lithium in THF <95JOC8>. 

Unlike in the previously mentioned species, compounds 1 and 8 were very active on T. platyurus. The LC50 value of the first compound (0.84 pmol/L) was comparable with its IC50 value found for S. capricornutum (0.80 pmol/L). Compounds 3, 10, 13 and 13a were inactive at the tested concentrations, while ent-labdanes 2 and 12 showed high values of LC5o. 

The biological activity of diterpenes is copiously reported in the literature. Singh et al. reviewed the biological activity of labdane diterpenes from 1987 to 1997.30 The antibacterial, antifungal, anti-inflammatory, cytotoxic and other... 

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