An azole, an amide and a limonoid from Vepris uguenensis (Rutaceae).

The limonoid derivative, methyl uguenenoate, the azole, uguenenazole, and the amide, uguenenonamide, together with the known furoquinoline alkaloids flindersiamine and maculosidine, and syringaldehyde have been isolated from the root of the East African Rutaceae Vepris uguenensis. While methyl uguenenoate and the furoquinoline alkaloids displayed mild antimalarial activity, the azole and amide were completely inactive.

Acridone and furoquinoline alkaloids from Teclea gerrardii (Rutaceae: Toddalioideae) of southern Africa.

The combined hexane/CH(2)Cl(2) extract of the stem bark of Teclea gerrardii (Rutaceae: Toddalioideae) has yielded two acridone alkaloids, 3-hydroxy-1-methoxy-N-methylacridone (tegerrardin A) (1) and 3-hydroxy-N-methyl-1-(gamma,gamma-dimethylallyloxy)acridone (tegerrardin B) (2), three known acridones (3-5), two known furoquinolines (6,7), and the acridone precursor tecleanone (8). Arborinine (3) and evoxine (6) displayed moderate antiplasmodial activity against the CQS D10 strain of Plasmodium falciparum, with IC(50) values of 12.3 and 24.5 microM, respectively.

Flavones and isoflavones from the west African Fabaceae Erythrina vogelii.

The CH(2)Cl(2)/MeOH extract of the stem bark of Erythrina vogelii (Fabaceae) from Nigeria has yielded two novel isoflavones, 7,4'-dihydroxy-8-(gamma,gamma-dimethylallyl)-2''zeta-(4''-hydroxyisopropyl)dihydrofurano[1'',3'':5,6]isoflavone (vogelin H) (1) and 7,4'-dihydroxy-8-[(2'''zeta,3'''-dihydroxy-3'''-methyl)butyl]-2'',2''-dimethyl-3'',4''-dehydropyrano[1'',4'':5,6]isoflavone (vogelin I) (2), a novel flavone, 7,4'-dihydroxy-2'',2''-dimethyl-3'',4''-dehydropyrano[1'',4'':5,6]flavone (vogelin J) (3), and eight known flavonoids.

Mexicanolide limonoids from the Madagascan Meliaceae Quivisia papinae.

An investigation of the seeds of the Madagascan Meliaceae Quivisia papinae has yielded five mexicanolide group limonoids, together with two known mexicanolide limonoids and two known triterpenoids. Quivisianolide A 9 possesses a hitherto unreported 9alpha,11alpha-epoxide ring, quivisianolide B 10 the corresponding delta(9(11)) double bond, and quivisianone 11 is a 17-keto seco-ring D compound.

Quassinoids from the leaves of the Madagascan Simaroubaceae Samadera madagascariensis.

An investigation of the leaves of the Madagascan Simaroubaceae Samadera madagascariensis has yielded three C18 quassinoids, 5beta,6-dihydrosamaderine A, 2-chlorosamaderine A, and samaderolactone A, and a C19 quassinoid, 3,4beta-dihydrosamaderine C, together with the known quassinoids samaderine A, samaderine B, and cedronin. The compounds isolated displayed little or no anti-tumour activity.

Furoquinoline alkaloids from the southern African Rutaceae Teclea natalensis.

The chloroform and ethyl acetate extracts of the leaves of Teclea natalensis have yielded two furoquinoline alkaloids, 6-[(2,3-epoxy-3-methylbutyl)oxy]-4,7-dimethoxyfuro[2,3-b]quinoline and 4,7-dimethoxy-6-[(3-methyl-2-butenyl)oxy]furo[2,3-b]quinoline, and the known alkaloids 4,7-dimethoxy-8-[(3-methyl-2-butenyl)oxy]furo[2,3-b]quinoline, flindersiamine and dictamnine.

N-Substituted acridone alkaloids from Toddaliopsis bremekampii (Rutaceae: Toddalioideae) of south-central Africa.

Toddaliopsins A-D, four novel 1,2,3-trioxygenated acridone alkaloids, have been isolated from the leaves of Toddaliopsis bremekampii. Toddaliopsins B-D are the first reported acridone alkaloids with substituted N-methyl groups, in the light of which the chemotaxonomic relationship of Toddaliopsis and Vepris is discussed. Toddaliopsin C possesses moderate anti-inflammatory activity, which may be related to the hydroxy group present at C-1.

Quivisianthone, an evodulone limonoid from the Madagascan Meliaceae Quivisia papinae.

An investigation of the seeds of the Madagascan Meliaceae Quivisia papinae has yielded quivisianthone, a novel evodulone group limonoid, together with the known azadiradione and two novel derivatives: 6 alpha-hydroxyazadiradione and 7-deacetyl-7-angeloyl-6 alpha-hydroxyazadiradione. Quivisianthone is the first reported evodulone group limonoid possessing both a ring A lactone and an azadiradione-type ring D.

Secondary metabolites from Cedrelopsis grevei (Ptaeroxylaceae).

From the hexane extract of the stem bark of Cedrelopsis grevei (Ptaeroxylaceae) was isolated the triterpenoid derivative, cedashnine, and the quassinoid, cedphiline, along with cedmiline, scoparone, beta-amyrin and sitosteryl glucoside.

Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis in U-937 leukemic cells.

Chemotherapeutics represent the main approach for the treatment of leukemia. However, the occurrence of adverse side effects and the complete lack of effectiveness in some cases make it necessary to develop new drugs. As part of our screening program to evaluate the potential chemotherapeutic effect of natural coumarins, we investigated the anti-leukemic activities of a series of six prenylated coumarins isolated from the stem bark of Toddalia asiatica (Rutaceae). Among these, 6-(3-methyl-2-butenyl)-5,7-dimethoxycoumarin (toddaculin) displayed the most potent cytotoxic and anti-proliferative effects in U-937 cells. To determine whether these effects resulted from induction of cell death or differentiation, we further evaluated the expression of several apoptosis and maturation markers. Interestingly, while toddaculin at 250 µM was able to induce apoptosis in U-937 cells, involving decreased phosphorylation levels of ERK and Akt, 50 µM toddaculin exerted differentiating effects, inducing both the capacity of U-937 cells to reduce NBT and the expression of differentiation markers CD88 and CD11b, but no change in p-Akt or p-ERK levels. Taken together, these findings indicate that toddaculin displays a dual effect as a cell differentiating agent and apoptosis inducer in U-937 cells, suggesting it may serve as a pharmacological prototype for the development of novel anti-leukemic agents.

Triterpenoid acids and lactones from the leaves of Fadogia tetraquetra var. tetraquetra (Rubiaceae).

Four triterpenoids isolated from the leaves of Fadogia tetraquetra var. tetraquetra, 3beta-hydroxy-11alpha, 12alpha-epoxyoleanan-28,13beta-olide (1), 3beta-hydroxyurs-11-en-28,13beta-olide (2), oleanolic acid (3), and ursolic acid (4), were evaluated for their antiviral and antibacterial properties. Compound 4 showed potent activity against the Semliki Forest virus with an IC50 of 14.7 microM, but was also found to be significantly cytotoxic (68% reduction in cell viability after 24 hours exposure at 50 microM) towards baby hamster kidney (BHK21) host cells. A viability assay on the mammalian human hepatocellular carcinoma (Huh-7) cell line showed no significant effects on intracellular ATP content after 48 hours exposure to compounds 1-4 at this concentration. Compound 4 also inhibited Staphylococcus aureus (MIC 12.5 microM), but was inactive against Enterobacter aerogenes, Escherichia coli, and Pseudomonas aeruginosa. Compounds 1-3 were inactive against all tested bacterial strains at 50 microM concentration.

Methyl gardenolate A, a novel cycloartenoid ester from the leaves of Combretum woodii (Combretaceae).

Isolation of the novel cycloartenoid ester methyl gardenolate A (3a), together with gardenolic acid A (2a) and the unusual triterpenoid xi-glutinol (D:B-friedoolean-5-en-3xi-ol) (1a) from the leaves of Combretum woodii support its differentiation from the closely related C. krausii.

Phragmalin limonoids from the Madagascan Meliaceae Neobeguea leandreana.

The combined hexane-CH(2)Cl(2) extract of the stembark of the Madagascan Meliaceae Neobeguea leandreana yielded three novel phragmalin limonoids, leandreanins A (1), B (2), and C (3). Leandreanins A (1) and B (2) are rare seco-ring D 17-keto compounds related to pseudrelone B, while leandreanin C (3) has an unprecedented acetoxy functionality at C-19.