Gastroprotective Effect and Cytotoxicity of Semisynthetic Jatropholone Derivatives

Abstract

The gastroprotective effect of the diterpenes jatropholone A, jatropholone B and 16 semisynthetic derivatives was assessed in the HCl/ethanol-induced gastric lesion model in mice and the cytotoxicity was determined towards fibroblasts and AGS cells. In a dose-response study, jatropholone B reduced gastric lesions by 65% at 6 mg/kg and jatropholone A by 54% at 100 mg/kg. The jatropholone B derivatives 9 - 14 and the compounds 15 - 18 were compared at a single oral dose of 25 mg/kg while the jatropholone A derivatives 2 - 7 were assessed at 100 mg/kg. A decrease in gastroprotective activity was observed for the ether as well as for the ester derivatives of jatropholone B. The methyl and propyl ethers of jatropholone A were more gastroprotective than the natural product. The placement of an additional methyl group at C-2 in the jatropholone B derivatives led to a loss of selectivity, the methyl and propyl ethers lack a gastroprotective effect. Jatropholone B was not toxic towards AGS cells and fibroblasts. Jatropholone A was active only against AGS cells. The gastroprotective effect of the epimeric jatropholones was selective showing a higher effect for jatropholone B. These results further support that the stereochemistry of the methyl group at C-2 in the jatropholones plays a relevant role in preventing the gastric lesions in mice. The compounds 3, 5 - 7, 10 and 12 - 18 are described for the first time.

Jatrocurcadiones A and B: two novel diterpenoids with an unusual 10,11-seco-premyrsinane skeleton from Jatropha curcas

“…6 These diterpenpoids showed broad range of bioactivities, such as anti-plasmodial, 7 anti-tuberculosis, 7 anti-inflammatory, 8 and especially cytotoxic activity. Previous investigations have proved that it was a rich source of structurally diverse diterpenoids related to premyrsinanes, some of which featured unprecedented skeletons, such as jatrophalactam possessing a novel 5/13/3 tricyclic skeleton, 4 spirocurcasone with a rare "spirorahamnofolane" scaffold, 5 and jatrophadiketone possessing an unique 6/6/6 tricyclic framework.…”

Environmental Impact of Genetically Modified Crops

“…However, some diterpenes are known for their antimicrobial and antitumour activities. For example, J. curcas was shown to contain jatropholone A and B (Ravindranath et al, 2004) which have been recently shown to have gastro-protective and cytotoxic effects (Pertino et al, 2007). Other terpenoids such as Jatropha trione and acetylaleuritolic acid obtained from other species of Jatropha have also been shown to have antitumour activities (Torrance et al, 1976(Torrance et al, , 1977.…”

“…Seed diterpenes and toxins as antimicrobial Goel et al (2007) Antitumour, molluscicidal and insecticidal Luo et al (2007); Jatropholone used to prevent gastric lesions Pertino et al (2007) Seed oil Biodiesel Kaushik et al (2007) Burkill (1985) Jatrophone is antineoplastic Biehl and Hecker (1986) …”

New jatropholane-type diterpenes from Jatropha curcas cv. Multiflorum CY Yang

“…Up until recently, more than 65 diterpenoids were identified from this genus 4 . Some of these have been proven to have the effects of antiinflammatory 5 , antiproliferation 6,7 , antiplasmodial 8 , antituberculosis 9 , and antitumor [9][10][11] .…”

“…Our first-time phytochemical study on the plant collected in Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, led to the isolation of three new jatropholane-type diterpenoids (1-3), along with seven known jatropholane analogs (4)(5)(6)(7)(8)(9)(10). Their structures were determined by analysis of the spectroscopic data.…”