Bioactive metabolites from the Andean flora. Antituberculosis activity of natural and semisynthetic azorellane and mulinane diterpenoids

Abstract

Natural products are recognized as an important source of new and better pharmaceuticals for the treatment of diseases such as tuberculosis. The azorellane and mulinane diterpenoids represent an interesting group of bioactive metabolites produced by Andean plants belonging to the Azorella, Mulinum, Laretia and Bolax genus. Testing of natural and semisynthetic azorellanes and mulinanes against two Mycobacterium tuberculosis strains showed that while most changes in the structure of the natural metabolites result in the loss of antituberculosis activity, methylation of the C-20 carboxyl group improves the biological activity of the corresponding derivatives.

A NOVEL NORMULINANE ISOLATED FROM Azorella compacta AND ASSESSMENT OF ITS ANTIBACTERIAL ACTIVITY

“…Compound 1 (Figure 1) and six known diterpenes ( Figure 2) were isolated from this extract. Known compounds were identified by comparison with authentic samples and with data from the literature [13][14][15][16][17] . Compound 1 was isolated as a colorless solid.…”

7-6-5 Tricarbocyclic Diterpenes

“…Azorellanes [14,20,[38][39][40][41][42][43][44][45][46][47][48][49][50] These compounds do not present a functionalized C-20 but in C-13 is always present an oxygenated functionality. Mulinanes show a great variety of A. compacta Antibacterial [33] 11,14-Dioxo-mulin12en-20-oic acid, 47…”

“…spinosa [37] A. compacta [17] Azorelaldehyde, 73 A. cryptantha [49] Yaretol, 74 A. madreporica Antituberculosis [14,50] yaretol 74, a rearranged mulinane whose structure was confirmed by X-ray diffraction but not its absolute configuration [50]. spinosa [37] A. compacta [17] Azorelaldehyde, 73 A. cryptantha [49] Yaretol, 74 A. madreporica Antituberculosis [14,50] yaretol 74, a rearranged mulinane whose structure was confirmed by X-ray diffraction but not its absolute configuration [50].…”

Antimicrobial Diterpenes from Azorella Species against Gram-Positive Bacteria

“…About 30 new or rare diterpenoids have been characterized from the tribe Mulinae, which have unique structural features so far unreported from natural and synthetic sources. These compounds possess mulinane, azorellane, yaretane and madreporane skeleta and have been so far only described in members of this tribe [1][2][3]. These metabolites possess various biological activities such as antibacterial, antiviral, antiprotozoal, and antituberculosis, as well as spermicidal, cytotoxic, antihyperglycemic, anti-inflammatory and analgesic effects [2,4,5,6].…”

“…(15 mg) [1], azorellanol(2) (15 mg) [3] and 13-α-hydroxyazorellane (3) (7 mg)[2]. Minor structural modifications of the natural compounds yielded two derivatives: 7-deacetylazorellanol (4) [2] and 7acetoxy-mulin-9,12-diene (5) [2].…”