Crotonkinins A and B and Related Diterpenoids from Croton tonkinensis as Anti-inflammatory and Antitumor Agents

Abstract

Cytotoxicity-guided phytochemical investigation of a methanolic extract of Croton tonkinensis afforded two new kaurane diterpenoids (1, 2) and 10 known ent-kaurane-type diterpenoids (3- 12). The structures of 1 and 2 were based on analysis of spectroscopic and mass spectral data. Compounds 3- 12 were identified by comparison of their spectroscopic and physical data with those reported in the literature. Selected compounds from this plant were examined for cytotoxic and anti-inflammatory activities. Compounds 4 and 9 showed the highest cytotoxic activity against the tested tumor cell lines. Compounds 3, 4, 6, 8, 9, and 11 had IC 50 values less than 5 microM and were more potent than the nonspecific NOS inhibitor L-NAME in inhibiting LPS-induced NO production.

Cembranolides from the stem bark of the southern African medicinal plant, Croton gratissimus (Euphorbiaceae)

“…Previous investigations of the genus Croton have yielded pimarane (Block et al, 2004), kaurane (Kuo et al, 2007 ), labdane (Garcia et al, 2006 ), clerodane (Garcia et al, 2006) and cembrane (Pudhom et al, 2007) diterpenoids, isoquinoline alkaloids (New World species only) (Charris et al, 2000 ) and triterpenoids (Block et al, 2004).…”

In vitro antituberculosis activity of diterpenoids from the Vietnamese medicinal plant Croton tonkinensis

“…Previously, the cytotoxicity of kaurane-type diterpenoids was found to be usually conferred by the 16-en-15-one basic structure. An O=C-CH=CH-system also modulates cytotoxicity, as this moiety is susceptible to nucleophilic attack [21]. Thus, although Croton diterpenoids possess a structure-activity relationship in terms of eukaryotic cell lines, it was surprising that the biological activity of Croton diterpenoids from CT against M. tuberculosis was circumvented as no studies were undertaken before the current study.…”

“…The biological activity of the ent-kaurane structure might be derived from the reactive centers, which contain an exomethylene group conjugated to a carbonyl group [11]. In addition, 18-hydroxy and 14-acetoxy substitution in the ent-kaurane structure was reported to contribute to cytotoxicity in the A549, MCF-7, KB and KB-VIN cell lines [21]. Previously, the cytotoxicity of kaurane-type diterpenoids was found to be usually conferred by the 16-en-15-one basic structure.…”

“…Although other solvent fractions (ethanol, nhexane, ethyl acetate fractions) also showed anti-TB activity, it was postulated that this antimycobacterial activity might be due to the presence of different diterpenoids in the CT extracts. The reasoning for this postulation was drawn from the previous studies as diterpenoids were found to be the main constituents of CT extracts (11)(12)(13)(14)(15)(20)(21)(22). Tuberculosis (TB) poses a global threat to mankind because of the rapid emergence of MDR-and XDR-TB strains, which are usually uncontrollable with the available treatment regimen.…”

Xây dựng phương pháp định tính, định lượng hoạt chất ent-7-hydroxy-15-oxokaur-16-en-18-yl acetate trong dược liệu khổ sâm cho lá (Croton tonkinensis Gagnep.)

“…Email: pththuong@hpmu.edu.vn https://doi.org/10.25073/2588-1132/vnumps.4067 học chính của khổ sâm cho lá là các diterpenoid thuộc nhóm ent-kaurane, trong đó hoạt chất chính là ent-7-hydroxy-15-oxokaur-16-en-18-yl acetate (ký hiệu là CT1), cũng cho tác dụng chống ung thư [4][5][6] và chống viêm rất mạnh trên mô hình thử in vitro (tế bào) [4][5][6][7], và mô hình in vivo [8]. Ngoài ra, các ent-kauran diterpenoid cũng có nhiều tác dụng dược lý quan trọng khác [4,9,10].…”