Anti-androgenic Triterpenoids from the Brazilian Medicinal Plant, Cordia multispicata.

Abstract

In the course of our program to find anti-androgenic constituents from plant sources, we have isolated anti-androgenic neoflavones and flavonoids from Dalbergia conchinchinensis 1) and prenyl flavones from Sophora flavescens. 2)In further screening of plant extracts, methanol extracts of Cordia multispicata (Boraginaceae) were shown to have potent activity. C. multispicata is a Brazilian medicinal plant that is used as an expectorant and as a drug for contusion, and is mainly distributed in the Amazon area. No chemical constituents have been reported from C. multispicata, 3) however, a few reports on the constituents from other Cordia sp. plants have appeared. The anti-androgenic constituents were isolated from leaves of C. multispicata by activity-guided fractionation, to give six new ursane type triterpenoids along with known oleanane and ursane triterpenes having relatively novel structures. This paper deals with the isolation and structural elucidation of the new triterpenes, 1-6 from C. multispicata and their inhibitory activity against testosterone 5a-reductase.A methanol extract of leaves of C. multispicata showing anti-androgenic activity was partitioned between AcOEt and H 2 O. The aqueous layer was further extracted with n-BuOH to give a n-BuOH soluble fraction and the aqueous layer. The AcOEt fraction showed the most potent anti-androgenic activity and was fractionated as described in the Experimental section to give new triterpenes, 1-6, along with known triterpenes, lantanolic acid (7), 4) 3-epipomolic acid (8), 5) lantic acid (9), 4) icterogenin (10), 6) lantadene A (11), 7) lantadene B (12), 7) ursomic acid (13) 8) and pomonic acid (14), 9) and the flavonols pachypodol (15) 10) and retusin (16), 11) which were recently reported as anti-emetic principles of Pogostemon cablin. 12)The high resolution (HR)-FAB-MS of 1 afforded a pseudo molecular ion [MH] ϩ at m/z 529.3533, corresponding to the molecular formula C 32 H 48 O 6 . The IR spectrum of 1 showed absorptions at 3434 (OH) and 1730 (carbonyl) cm Ϫ1. 52-1 Yada, Shizuoka, 422-8526, Japan, Life Science Center, Lion Corporation, c 100 Tajima, Odawara, 256-0811, Japan, and Division of Pharmacognosy and Phytochemistry, National Institute of Health Sciences, d 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan. Received January 29, 2001; accepted April 13, 2001 Compounds 1-6 were isolated from the AcOEt soluble fraction of leaves of the Brazilian medicinal plant, Cordia multispicata, and their structures were elucidated to be 3b b,25-epoxy-21b b-acetoxy-3a a,22b b-dihydroxyurs-12-en-28-al (1), 3b b,25-epoxy-28-acetoxy-3a a,21b b,22b b-trihydroxyurs-12-ene (2), 21b b-acetoxy-22b b-hydroxy-3-oxours-12-en-28-al (3), 28-acetoxy-6b b,21b b,22b b-trihydroxy-3-oxours-12-ene (4), 21b b,22b b-dihydroxy-3-oxours-12-en-28-al (5) and 3b b,21b b,22b b-trihydroxyurs-12-en-28-al (6), respectively, by means of spectral data, especially two dimensional NMR techniques. Triterpenes having the hemiketal structure at the A-ring, an acyloxy group at C-22 and/or ket...

Determination of the phenolic content and antioxidant potential of crude extracts and isolated compounds from leaves ofCordia multispicataandTournefortia bicolor

“…The genus Cordia, consisting of about 325 species (Kuroyanagi et al, 2001), is probably the largest in the family and it is widely distributed in the warmer regions of the world, but is especially well represented in Central and South America (Nowicke & Ridgway, 1973). C. multispicata Cham., a Brazilian medicinal plant known as "carucaá", is used as an expectorant and as a drug for contusion (Kuroyanagi et al, 2001). Previous phytochemical study from leaves of this species has yielded only ursane, oleanane and dammarane triterpenes containing anti-androgenic activity (Kuroyanagi et al, 2001(Kuroyanagi et al, , 2003.…”

“…C. multispicata Cham., a Brazilian medicinal plant known as "carucaá", is used as an expectorant and as a drug for contusion (Kuroyanagi et al, 2001). Previous phytochemical study from leaves of this species has yielded only ursane, oleanane and dammarane triterpenes containing anti-androgenic activity (Kuroyanagi et al, 2001(Kuroyanagi et al, , 2003. On the other hand, the genus Tournefortia possesses about 150 species of shrubs or wood vines found also in the warmer regions of the world, but centering in the neotropics (Nowicke & Skvarla, 1974).…”

Chemical composition and larvicidal activity of the essential oils of Cordia leucomalloides and Cordia curassavica from the Northeast of Brazil

“…1 Some of its species yield excellent wood naturally resistent to attack of several organisms, 2,3 while others are widely used in traditional medicine in several parts of the world. 4 13 and C. globosa (Jacq.) H.B.K.…”

“…1 Some of its species yield excellent wood naturally resistent to attack of several organisms, 2,3 while others are widely used in traditional medicine in several parts of the world. [4][5][6] Various phytochemical studies on Cordia species have been published, revealing a great number and diversity of secondary metabolites including triterpenes, 4 J. Braz. Chem.…”

Estudo dos componentes lipídicos das sementes de três espécies do gênero Cordia L. (Boraginaceae)

“…As principais substâncias encontradas nesta família são alcalóides, quinonas, naftoquinonas, saponinas, taninos, ácidos fenólicos, alantoínas, mucilagens, polissacarídeos, flavonóides, ciclitóis e ácidos graxos de interesse terapêutico e nutricional, como o ácido gamalinolênico (FELL;PECK, 1968;VELASCO;GOFFMAN, 1999;KUROYANAGI et al, 2001).…”