COX-1, COX-2 Inhibitors and Antifungal Agents from Croton hutchinsonianus

Abstract

Croton hutchinsonianus HOSSEUS belongs to the family Euphorbiaceae. It is a shrub or small tree reaching 4-5 meters high and native to Thailand,1) where it is commonly called "Plao phae". In this paper, we describe the isolation and structure elucidation of newly isolated 3Ј-(4Љ-hydroxy-3Љ,5Љ-dimethoxyphenyl)-propyl benzoate, 3Ј-(4Љ-hydroxyphenyl)-propyl benzoate and four known compounds [3Ј-(4Љ-hydroxy-3Љ-methoxyphenyl)-propyl benzoate, poilaneic acid, farnesyl acetone and 4-hydroxybenzaldehyde] from the branches of this plant. The complete NMR assignment of 3Ј-(4Љ-hydroxy-3Љ-methoxyphenyl)-propyl benzoate was established for the first time in this paper. The inhibitory activities against the enzymes COX-1 and COX-2 and antifungal activities against Candida albicans were also performed on some of the isolated products. Results and DiscussionCompounds 1-6 were obtained from the ethyl acetate extract of C. hutchinsonianus after purification by Cosmosil C 18 -OPN, Sephadex LH 20 and silica gel column chromatography.HR-FAB-MS of 1 suggested a molecular formula of C 18 H 20 O 5 corresponding to nine degrees of unsaturation present in the molecule. The IR spectrum demonstrated the presence of a hydroxyl group (3446 cm Ϫ1) and a carbonyl group (1708 cm Ϫ1 ). The 1 H-NMR spectral data (Table 1) showed the presence of two benzene rings which was readily confirmed by analysis of the 1 H-1 H COSY, HMQC and HMBC spectral data. The 1 H-NMR spectral data showed three methylene groups (H-1Ј, H-2Ј, H-3Ј) bridging between benzoate and aromatic rings, two methoxyls at d 3.86 (each 3H, s) and one D 2 O-exchageable hydroxyl proton at d 5.40 appearing as a broad singlet suggestive of the phenylpropyl benzoate moiety with the substituents of hydroxyl and methoxyl groups on the aromatic ring. In addition, HMBC data for 1 conclusively demonstrated the correlations of methylene protons H-1Ј to C-1 and H-2Ј to C-1Љ and H-3Ј to C-2Љ and C-1Ј respectively. The 13 C-NMR spectrum showed the signal of carbonyl ester at d 166.6. The positions of two methoxyl groups and one hydroxyl group were established employing the HMBC technique (correlations as shown in Fig. 1). All data are consistent with the structure of 3Ј-(4Љ-hydroxy-3Љ,5Љ-dimethoxyphenyl)-propyl benzoate.Compound 2 has already been isolated from the flower of Gardenia taitensis DC, 2) however no NMR spectral data has been reported. The 1 H-and 13 C-NMR data of 2 are shown in Table 1.Compound 3 had a molecular formula of C 16 H 16 O 3 based on HR-FAB-MS. The 1 H-and 13 C-NMR data of 3 (Table 1) was similar to those of 1 except for the absence of two methoxyl groups at C-5Љ and C-3Љ. The 1 H-NMR spectral data of 3 showed the presence of the para-substituted benzene ring at d 7.08 (2H, d, Jϭ8.4 Hz, H-2Љ, H-6Љ); d 6.77 (2H, d, Jϭ8.4 Hz, H-3Љ, H-5Љ). The 2D NMR experiment on 3 also produced very similar results, indicating that both 1 and 3 were closely related.Compounds 1-3 were tested for antifungal activity against Candida albicans. They showed moderate activity * To whom corresponde...

Traditional uses, chemistry and pharmacology of Croton species (Euphorbiaceae)

“…From the aerial parts of C. hutchinsonianus Hos., a species native in Thailand, two new compounds were isolated, namely 3'-(4"-hydroxyphenyl)-propyl benzoate and 3'-(4"-hydroxy-3",5"-dimethoxyphenyl)-propyl benzoate (23), together with the known 3'-(4"-hydroxy-3"-methoxyphenyl)-propyl benzoate. 130 Lignoids are common in plant groups bearing benzylisoquinolines and related alkaloids (derived biosynthetically from tirosine), such as Ranunculales and Magnoliales. As was commented above, some Croton species possess this class of alkaloids.…”

Labdane-type diterpenoids from Croton laevigatus

“…The IR spectrum exhibited absorption bands due to hydroxyl (3381, 3296 cm À1 ), conjugated carbonyl (1683 cm À1 ) and olen (1625 cm À1 ) functionalities. The 1 H and 13 C NMR spectroscopic data of 14 (Experimental section and Table 2) were similar to those of 13, except for changes at CH [2][3][4][5][6]1H,dd,J ¼ 13.6,4.4 Hz,d H 2.11,1H,d,J ¼ 13.6 Hz;d C 29.0), 1H,d,J ¼ 4.0 Hz;d C 62.3),, and C-9 (d C 162.4). These data suggested that a hydroxyl group should be bonded to C-7 and a double bond was at C-8.…”

“…The 1 H-1 H COSY experiment showed connectivity of three moieties: I: 1 CH 2 -2 CH 2 -3 CH 2 ; II: 5 CH-6 CH 2 -7 CH 2 ; and III: 9 CH-11 CH(O)-12 CH 2 . The HMBC correlations from CH 3 -19 (d H 0.79, 3H, s) to C-3 (d C 35.1), C-5 (d C 44.4), and C- 18 (d C 15.7); from H [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]each 1H,d,J ¼ 11.2 Hz) to C-3, C-5, and C-19 (d C 17.7); and from H 2 -2 (d H 1.50 and 1.60, each 1H, m) to C-4 (d C 37.5) indicated that C-4 connected units I and II together. The HMBC correlations from CH 3 -20 (d H 0.96, 3H, s) to C-1 (d C 41.4), C-5, and C-9 (d C 66.0) and from H 2 -1b (d H 0.96, 1H, m) to C-9 suggested that C-10 (d C 35.9) connected units I and III together.…”

“…The HMBC correlations from CH 3 -20 (d H 0.96, 3H, s) to C-1 (d C 41.4), C-5, and C-9 (d C 66.0) and from H 2 -1b (d H 0.96, 1H, m) to C-9 suggested that C-10 (d C 35.9) connected units I and III together. Furthermore, the HMBC correlations from H-9 (d H 1.57, 1H, d, J ¼ 2.0 Hz) to C- 17 (d C 78.5),1H,td,J ¼ 5.2,2.4 Hz) and H 2 -6 (d H 1.32 and 1.60, each 1H, m) to C-8 (d C 80.1), and from H [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]each 1H,d,J ¼ 9.6 Hz) to C-7 (d C 33.3), C-9, IR spectrum showed absorption bands for hydroxyl (3422 cm À1 ), ester carbonyl (1735 cm À1 ) and olen (1676 cm À1 ) functionalities. The 1 H and 13 C NMR spectroscopic data (Tables 1 and 2) of 3 resembled those of 1 and 2, sharing the same AB rings, and also belongs to nor-labdane-type diterpene series.…”

“…Moreover, the 1 H and 13 C NMR spectroscopic data also showed an extra acetyl group signal at d H 2.13 (s, 3H; d C 20.9, 171.1). The HMBC experiment demonstrated correlations of H [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]J ¼ 11.2,1.2 Hz;4.38,d,J ¼ 11.2 Hz) to C-21 (d C 171.1), which indicated the acetoxyl group attached to C-17 in 3. The NOESY spectrum showed correlations of H-9 to H-5 and H 2 -17 to CH 3 -20, which indicated that the H 2 -17 was b-oriented, and the 8-OH and H-9 were a-oriented.…”