Search

Seven alkaloids ( 1 – 7 ) were isolated from the stem bark of Alangium longiflorum . Compound 1 , (−)-10- O -demethylisocephaeline, was isolated for the first time as a naturally occurring product from a plant source. All structures were elucidated by detailed spectroscopic analysis. Biological evaluation showed that 2 , 10- O -demethylcephaeline, exhibited potent cytotoxic activity against human lung carcinoma (A549) and breast adenocarcinoma (MCF-7) with ED 50 values of 0.013 and 0.062 μM, respectively. The stereoisomer 1 was less potent than 2 , and related compounds with different hydroxy/methoxy substitution patterns were also less potent or inactive. Thus, compound 2 merits attention as a cytotoxic lead for further study.

As part of a study on potential antitumor agents from rainforest plants, two new pterocarpans, rautandiol A (1) and rautandiol B (2), together with eight known compounds, were isolated from Neorautanenia mitis. Among the compounds isolated, rotenone (3) and 12-hydroxyrotenone (4) showed significant cytotoxic activity with IC(50) values of 0.008-0.010 and 0.04-0.06 microg/mL against MCF-7 and A-549 cells, respectively.

As part of a study on potential antitumor agents from rainforest plants, two new pterocarpans, rautandiol A (1) and rautandiol B (2), together with eight known compounds, were isolated from Neorautanenia mitis. Among the compounds isolated, rotenone (3) and 12-hydroxyrotenone (4) showed significant cytotoxic activity with IC(50) values of 0.008-0.010 and 0.04-0.06 microg/mL against MCF-7 and A-549 cells, respectively.

In a continuing structure-activity relationship study of potent anti-HIV agents, seven new triterpene derivatives were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, moronic acid derivatives 19, 20 and 21 showed significant activity in HIV-1 infected H9 lymphocytes. Compounds 19 and 20 were also evaluated against HIV-1 NL4−3 and drug resistant strains in the MT-4 cell line. Compounds 19 and 20 showed better antiviral profiles than the betulinic acid analog 8 (PA-457), which has successfully completed a Phase IIa clinical trial. Compound 20 showed potent anti-HIV activity with EC50 values of 0.0085 μM against NL4−3, 0.021 μM against PI-R (a multiple protease inhibitor resistant strain), and 0.13 μM against FHR-2 (an HIV strain resistant to 8), respectively. The promising compound 20 has become a new lead for modification, and further development of 20-related compounds as clinical trial candidates is warranted.

In continuation of our previous report, cimigenol (1) and 15 related compounds were screened as potential antitumor promoters by using the in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA)––induced Epstein-Barr virus early antigen (EBV-EA) activation assay. Cimigenol-3,15-dione (2) displayed the greatest potency (100% inhibition at 1000 mol ratio/TPA) and consequently was further examined for antitumor-promoting activity in a two-stage carcinogenesis assay of mouse skin tumors (DMBA/TPA). In this assay, compound 2 showed significant activity, reducing the number of papillomas per mouse to 48% of the control group at 20 weeks. In addition, compounds 1 and 2 were examined for antitumor-initiating activity in a two-stage carcinogenesis assay of mouse skin tumors induced by peroxynitrite as an initiator and TPA as a promoter. Results showed that these two triterpenoids were almost equipotent with epigallocatechin gallate (EGCG) and slightly more potent than tocinol (group V), the positive controls. Thus, compounds 1 and 2 exhibited not only strong antitumor-promoting activity but also significant antitumor-initiating effect on mouse skin. These data suggest that both compounds might be valuable chemopreventors.

Cimigenol ( 1 ) and 39 related compounds were screened as potential antitumor promoters by examining the ability of the compounds to inhibit Epstein–Barr virus early antigen (EBV-EA) activation (induced by 12- O -tetradecanoylphorbol-13-acetate) in Raji cells. Structure–activity relationship analysis indicated that compound 1 showed the highest activity and also exhibited significant inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These data suggest that 1 and the related compounds might be valuable anti-tumor promoters.

Synthese d'esters ethylique et phenylique des acides amino-, et guanidino-naphtoiques et tetrahydro-1,2,3,4 naphtoique (inhibiteur de serine proteinase)

The structure of procurcumenol, a new sesquiterpenic keto-alcohol isolated from zedoary, Curcuma zedoaria (Zingiberaceae), has been shown to be I.

Guanidino-ester derivatives were synthesized and evaluated for inhibitory activities against trypsin, plasmin, kallikrein, thrombin and Cl esterase, as well as on in vitro complement-mediated hemolysis. Among the compounds synthesized, phenyl α-ethyl-p-guanidinocinnamate (IVg) and phenyl α-propyl-p-guanidinocinnamate (IVh) exhibited potent and selective Cl esterase inhibition (IC50 : 7×10-6 and 6×10-6 M, respectively) and 6-methyl-3-pyridyl α-ethyl-p-guanidinocinnamate (IVi) markedly suppressed complement-mediated hemolysis (86% inhibition at 1×10-3M).

From zedoary, Curcuma zedoaria (Zingiberaceae), a sesquiterpenoid curdione, C15H24O2, has been isolated and shown to be germacr-1 (10)-ene-5, 8-dione (I) based on the following evidence. The presence of a β-methyl-β, γ-unsaturated ketone and an isolated ketone group in the germacrane skeleton has been indicated by spectral determinations of curdione and its reduction product, the diol (IV), which is reversible to curdione on oxidation, and by dehydrogenation of the diol (IV) to S-guaiazulene (VII). The location of the two carbonyls has been established by the transformation of its dihydro-derivative (III) to the enone (VIII) whose structure has been confirmed by its spectral properties and by its conversion into vetivazulene (XI).

Curcumenol, C15H22O2, a new sesquiterpenic constituent of zedoary, Curcuma zedoaria (Zingiberaceae), has been shown to be represented by formula I on the basis of the following evidence. Chemical and physico-chemical properties of curcumenol and its derivatives indicate that curcumenol has a secondary methyl, a vinylic methyl on a trisubstituted double bond in which the carbon bearing a vinyl hydrogen is a to a quaternary carbon, an isopropylidene, and a hemiketal linkage whose carbon terminal is carrying no hydrogen. The carbon skeleton and the location of the hemiketal system have been established by the transformation to S-guaiazulene (V) and to the five-membered ring ketones (VII and VIII), respectively.

A new sesquiterpenic furano-ketol, curcolone, C15H18O3, has been isolated from zedoary, Curcuma zedoaria (Zingiberaceae). Physico-chemical studies of curcolone and its derivatives have enabled a decision to be made in favor of I as a representation of the structure and stereochemistry of the ketol.

Extraction of Zedoary (Curcuma zedoaria (Zingiberaceae)) has afforded a new sesquiterpenoid, curcumol, of the empirical formula C15H24O2. It has been shown to contain a vinylidene group and a hemiketal system. The guaiane carbon skeleton has been established by its dehydrogenation giving S-guaiazulene (IV). Curcumol has been ozonized to give the norketone (IX) which has been converted into the acid (X) and the lactone (XII). Spectroscopic study of these derivatives and other evidence show curcumol to be represented by formula I (R=H).