Trachylobane and kaurane diterpenes from Croton floribundus spreng

Abstract

Recebido em 20/7/12; aceito em 16/12/12; publicado na web em 14/5/13A new trachylobane diterpene ent-trachyloban-18,19-diol (1) was isolated from root bark of Croton floribundus, along with known diterpenes ent-trachyloban-19-oic acid (2), 15b-hydroxy-ent-trachyloban-19-oic acid (3), ent-trachyloban-19-ol (4), ent-kaur-16-en-19-oic acid (5), ent-kaur-16-ene-6a,19-diol (6) and ent-16a-hydroxykaur-11-en-19-oic acid (7). ent-trachyloban-18,19-diol (1) was submitted to derivatization reactions affording four new compounds (8)(9)(10)(11). Cytotoxic activity of diterpenes 1, 3, 4, 7-11 against three human cancer cell lines was evaluated. No compounds showed cytotoxic potential with IC 50 values greater than 25 mg/mL. Compound 6 was evaluated against five human cancer cell lines, showing moderate effect against three cancer cell lines, MDA-MB-435, with IC 50 values of 14.32, 13.47 and 12.1 mg/mL, respectively.Keywords: diterpenes; Croton floribundus; Euphorbiaceae. INTRODUCTIONTrachylobane and kaurene are diterpenoids biosynthetically derived from the monocyclic membrane. Kaurenes have been reported in several families of higher plants, with kaurenoic acid and its natural derivatives found particularly in the Asteraceae and Euphorbiaceae families. 1 These compounds have been largely cited as cytotoxic, antitumoral, genotoxic, antiinflammatory, antibacterial, antifungal and moluscidal. [2][3][4] On the other hand, trachylobane is found in some species of Euphorbiaceae, 5 Annonaceae, 6 Asteraceae, 7 Lamiaceae 8 and Leguminosae. 9 Although the biological activities of trachylobane compounds are poorly investigated, they are cited to possess vasorelaxant and cytotoxic properties. 10As part of an investigative effort to find bioactive diterpenoids in native species from Northeastern Brazil flora, this study reports the phytochemical investigation of the root bark of Croton floribundus Spreng., a tree with ethnobotanical use in the treatment of syphilis and ulcers.11 In this work, the new ent-trachyloban-18,19-diol (1) is reported, along with the known ent-trachyloban-19-oic acid (2), 12 ent-15b-hydroxytrachyloban-19-oic acid (3), 13 ent-trachyloban-19--ol (4), 12 ent-kaur-16-en-19-oic acid (5), 14 ent-kaur-16-en-6a,19-diol (6) 15 and ent-16a-hydroxykaur-11-en-19-oic acid (7). 16 ent-trachyloban-18,19-diol 1 was derivatized to the diacetate, dimethoxyl and diallyl derivatives 8-10, respectively. In addition, an unusual oxidized product 11 was obtained by oxidation with PCC and chromic acid. The cytotoxicity of the compounds 1, 3, 4, 6-11 against a small panel of cancer cell lines was evaluated (Figure 1). Vol. 36,No. 6 were attributed to two oxymethylene groups attached to a quaternary carbon. In addition, the presence of the shielded doublets at d 0.58 (d, J = 7.5 Hz, H-12) and 0.83 (dd, J = 7.5 and 2.4 Hz, H-13) of a tetrasubstituted cyclopropane ring suggested that 1 belongs to the trachylobane series. RESULTS AND DISCUSSIONChemical shifts and comparative analysis of BB and DEPT- 13C NMR spectra revealed 20 lines...

Study of Anti-Tuberculosis Activity Behaviour of Natural Kaurane and Trachylobane Diterpenes Compared with Structural Properties Obtained by Theoretical Calculations

“…As shown in previous works, the exudate from leaves of P. punctulata indeed is comprised of terpenoids, among them diterpenes from the classes of kauranes and trachylobanes [9,11,12]. Kauranes have already been reported for several families of higher plants and some of them have been cited as anti-inflammatory, antibacterial, antifungal, antitumor, and cytotoxic agents [13]. On the other hand, the biological activities of trachylobanes are poorly investigated, although they already presented vasorelaxant and cytotoxic properties [13].…”

“…sequential column chromatography with different eluents as described [9,12] and performing careful purification, substances 1 to 7 can be achieved in good yields and in adequate purity. The identification of all studied compounds was undertaken by comparison of 1 H and 13 C NMR data from those substances with data reported in the literature [9,12,13].…”

“…Kauranes have already been reported for several families of higher plants and some of them have been cited as anti-inflammatory, antibacterial, antifungal, antitumor, and cytotoxic agents [13]. On the other hand, the biological activities of trachylobanes are poorly investigated, although they already presented vasorelaxant and cytotoxic properties [13]. Due to our research interest in terpenoids [14][15][16][17], especially diterpenes and their biological activities [18][19][20], we worked with kaurane and trachylobane diterpenes that were available in the leaf exudate of Psiadia punctulata [9,11,12], and shown in Figure 1.…”

New and Antifungal Diterpenoids of Sunflower against Gray Mold

“…Thirteen known compounds were identified as ent -9 β -dihydroxy-15 α -(3-methylbutanoyloxy)-16-kauren-19-oic acid ( 5 ), , ent -(9 β , 15 α )-dihydroxy-kaur-16-en-19-oic acid ( 6 ), phyllocladene ( 7 ), grandifloric acid ( 8 ), 15 α -hydroxy-kaur-16-en-18-oate ( 9 ), 15-(2,3-dihydroxy-2-methyl-1-oxobutoxy)-kaur-16-en-18-oic acid ( 10 ), ent -16-oxo-17-norkauran-19-oic acid ( 11 ), ent -16 α ,17-dihydroxy-kauran-19-oic acid ( 12 ), ent -17-hydroxykaur-15­(16)-en-19-oic acid ( 13 ), 15 α -hydroxy-wedeliseccokaurenolide ( 14 ), 3 β -acetoxywedelia-seco-kaurenolide ( 15 ), 15 β -hydroxy- ent -trachyloban-19-oic acid ( 16 ), and 7 β -hydroxytrachyloban-19-oic acid ( 17 ) by comparison of their spectral data with literature (Figures S45–S70, Supporting Information).…”

Antiproliferative Activity of Flavonoids fromCroton sphaerogynusBaill. (Euphorbiaceae)

“…Ent-kaurane diterpenoids from Croton tonkinensis have activity against colorectal cancer cells [ 13 ]; ent -kaur-16-ene-6a,19-diol from C. floribundus Spreng. exhibited a moderate effect against MDA-MB-435 (melanoma), HCT-8 (colorectal adenocarcinoma), and HCT-116 (colorectal adenocarcinoma) cell lines [ 14 ]. Isopimara-7,15-dien-3b-ol from C. zambesicus showed weak cytotoxic activity against cancer (HeLa, human cervix carcinoma cells; HL-60, human promyelocytic leukemia) and noncancer (WI-38, human lung fibroblast) cell lines [ 15 ].…”