A New Antitubercular Mulinane Diterpenoid from Azorella madreporica Clos

Abstract

Bioactivity-guided fractionation of the petroleum ether extract of Azorella madreporica Clos has led to the isolation of the novel, antitubercular mulinane diterpenoid 1. The structure has been elucidated on the basis of its 1D and 2D NMR spectra and by comparison with mulinolic acid 2 and a dehydration product 3 obtained from 1. The MIC of 1 for growth inhibition of the H37Rv strain of Mycobacterium tuberculosis was determined as 20 microg/mL. LC-MS and NMR have suggested the presence of this new compound in four other species of Azorella.

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

“…The only bioactive mulinane, 14, displayed moderate antituberculosis activity. The antituberculosis activity of 2 is in agreement with that reported for its C-13 epimer, 13-a-hydroxy-azorellane (1), previously isolated from A. madreporica (Wächter et al 1998). However, while 2 and its epimeric C-7-acetylated derivative 3 showed a similar level of activity, 7, the C-7 acetylated derivative of 2, was not active.…”

“…1) (Loyola et al 1990a(Loyola et al , b, 1991(Loyola et al , 1996(Loyola et al , 1997a(Loyola et al , b, 1998(Loyola et al , 2002. These diterpenoids have displayed a wide variety of interesting biological activities, including antiprotozoal (Neira et al 1998;Loyola et al 2001aLoyola et al , b, 2004, antibacterial (Wächter et al 1999), antiviral (Abdel-Malek et al 1996, spermicidal (Morales et al 2003), cytotoxic (Mongelli et al 1997(Mongelli et al , 2000, antihyperglycemic (Fuentes et al 2005), antiinflammatory and analgesic (Delporte et al 2003;Bórquez et al 2007), and at least one mulinane diterpenoid, 9,12-cyclomulin-13-ol (1), has been reported as having antituberculosis activity (Wächter et al 1998). As a result of this, and as part of a project directed towards the search for natural antituberculosis agents, we have recently investigated the in vitro antituberculosis activity of a series of natural and semisynthetic azorellane and mulinane diterpenoids, when tested against two strains of Mycobacterium tuberculosis using the Alamar-blue assay (MolinaSalinas et al 2006(MolinaSalinas et al , 2010a.…”

Azorellane diterpenoids from Laretia acaulis inhibit nuclear factor‐kappa B activity

“…Azorellane diterpenoids have been demonstrated to have interesting biological activities such as antitubercular (Wachter et al, 1998), trichomonicidal (Loyola et al, 2001b), antiinflammatory (Delporte et al, 2003), contraceptive (Morales et al, 2003), anti-Trypanosoma cruzi (Araya et al, 2003), antiplasmodial (Loyola et al, 2004) and antihyperglycemic (Fuentes et al, 2005) effects. However, besides their high structural similarity to other anti-NF-κB sesquiterpenes lactones derived from the plant kingdom, the activity of these tetracyclic diterpenoids has never been investigated.…”

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…”