Diprenylated Indole Alkaloids from Fruits of Hexalobus monopetalus.

New hexalobine type alkaloid, 5-(2″,3″-epoxy-3″-methylbutyl)-3-(3'-hydroxy-3'-methyl-1'-acetyloxy-but-2'-yl)indole (1) alongside the known hexalobines 3-(2',3'-dihydroxy-3'-methylbutyl)-5-(3″-methylcrotonoyl) indole (2), 3,5-hexalobine C (3) and 3,5-hexalobine D (4) were isolated from fruits of Hexalobus monopetalus. Compounds 3 and 4 exhibited antifungal activity against Candida albicans.

Antifungal Enantiomeric Styrylpyrones from Sanrafaelia ruffonammari and Ophrypetalum odoratum.

Phytochemical investigation of Sanrafaelia ruffonammari Verd and Ophrypetalum odoratum Diels that belongs to the rare genera confined to East African coastal forests led to the isolation of enantiomeric styrylpyrone dimer, (±)-5-methoxy-7-phenyl-[4-methoxy-2-pyronyl]-1-(E)-styryl-2-oxabicyclo-[4.2.0]-octa-4-en-3-one (1) alongside (+)-6-styryl-7,8-epoxy-4-methoxypyran-2-one (2) and the enantiomeric (+)- (3) and (-)-6-styryl-7,8-dihydroxy-4-methoxypyran-2-ones (4). Their structures were established by means of spectroscopic methods. In this paper we reveal for the first time the occurrence of styrylpyrones in East African biodiversity. (+)-6-Styryl-7,8-epoxy-4-methoxypyran-2-one (2) and the dihydroxystyrylpyrone enantiomer (3) showed in vitro antifungal activity against Candida albicans at a concentration of 24.4 and 26.2 µM with zones of inhibition of 17 and 9 mm, respectively. Compound 2 exhibited strong activity in the brine shrimp test with LC50 = 1.7 µg/mL. Their high cytotoxic and antifungal activities render them candidates for further scientific attention for drug development programs against cancer and microbial infections.

New antimicrobial, mosquito larvicidal and other metabolites from two Artabotrys species.

Azabicycloheptenoylditerpene 1-((2E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraenyl)-2-azabicyclo[2.2.1]hept-5-en-3-one (artamodamide, 1), diphenylpentanoid (E)-1,5-bis(4-hydroxyphenyl)-pent-1-en-3-one (artamenone, 2) and N-methoxy-5-oxoaporphinoid (artamonteirine, 3) were isolated as new metabolites from Artabotrys modestus Diels ssp macranthus Verdc. and Artabotrys monteiroae Oliv. (Annonaceae), together with several known compounds. Structures of the isolated compounds were established based on analysis of their spectroscopic data. Some of the compounds exhibited antimicrobial activity (minimum inhibitory concentration values between 2.5 and 20 µg mL⁻¹) and varying levels of mosquito larvicidal potency. These results further indicate the versatility of the family Annonaceae in accumulating bioactive natural products with diverse chemical structures and wide spectra of biological activities, and hence suggesting the need to conserve Annonaceae species that are potentially vulnerable to extinction.

Toussaintines A-E: antimicrobial indolidinoids, a cinnamoylhydrobenzofuranoid and a cinnamoylcyclohexenoid from Toussaintia orientalis leaves.

Toussaintine A (N-cinnamoyl-5,6-dehydro-4-hydroxyindolidin-2,7-dione), toussaintine B (N-cinnamoyl-5,6-dehydro-4,7-dihydroxyindolidin-2-one), toussaintine C (N-cinnamoyl-5,6-dehydro-4-hydroxyindolidin-7-one), toussaintine D (N-cinnamoyl-2-amino-4-hydroxy-7-oxo-2,3,8,9-tetrahydrobenzofuran) and toussaintine E (N-cinnamoyl-1-acetoxymethyl-2-amino-1-hydroxycyclox-5-en-4-one) were isolated as antibacterial and antifungal constituents of the leaves of Toussaintia orientalis Verdc. (Annonaceae) and their structures established from analysis of spectroscopic data. The compounds belong to a series of variously cyclized aminocinnamoyl tetraketide derivatives, showing the importance of rarely occurring Annonaceae species as sources of structurally diverse natural products.

Constituents of the essential oil of Suregada zanzibariensis leaves are repellent to the mosquito, Anopheles gambiae s.s.

In traditional African communities, repellent volatiles from certain plants generated by direct burning or by thermal expulsion have played an important role in protecting households against vectors of malaria and other diseases. Previous research on volatile constituents of plants has shown that some are good sources of potent mosquito repellents. In this bioprospecting initiative, the essential oil of leaves of the tree, Suregada zanzibariensis Verdc. (Angiospermae: Euphobiaceae) was tested against the mosquito, Anopheles gambiae s.s. Giles (Diptera: Culicidae) and found to be repellent. Gas chromatography (GC), GC-linked mass spectrometry (GC-MS) and, where possible, GC-co-injections with authentic compounds, led to the identification of about 34 compounds in the essential oil. About 56% of the constituents were terpenoid ketones, mostly methyl ketones. Phenylacetaldehyde (14.4%), artemisia ketone (10.1%), (1S)-(-)-verbenone (12.1%) and geranyl acetone (9.4%) were the main constituents. Apart from phenylacetaldehyde, repellent activities of the other main constituents were higher than that of the essential oil. The blends of the main constituents in proportions found in the essential oil were more repellent to An. gambiae s.s. than was the parent oil (p < 0.05), and the presence of artemisia ketone in the blend caused a significant increase in the repellency of the resulting blend. These results suggested that blends of some terpenoid ketones can serve as effective An. gambiae s.s. mosquito repellents.

Geranylbenzoquinonoids from Lettowianthus stellatus fruits.

The geranylbenzoquinonoids 7-(3,7-dimethylocta-2,6-dienyl)-5-hydroxy-3H-benzofuran-2-one (lettowienolide), dimethyl 2,3-bis-[5-(3,7-dimethylocta-2,6-dienyl)-3,6-dioxocyclohexa-1,4-dienyl]-succinate (lettowiquinone), 2-(3,7-dimethylocta-2,6-dienyl)-6-[7-(3,7-dimethylocta-2,6-dienyl)-5-hydroxybenzofuran-2-yl]-[1,4]benzoquinone (lettowifuraquinone), methyl [3-(3,7-dimethylocta-2,6-dienyl)-6-methyl-5-(3-methylbut-2-enyl)-1,4-dioxo-1,5, 8,8a-tetrahydro-4H-nathphalen-4a-yl)]-acetate (lettowinone) and methyl [6-hydroxy-2-methyl-2-(4-methylpent-3-enyl)-2H-chromen-8-yl]-acetate (lettowipyraquinol) were isolated from fruits of Lettowianthus stellatus Diels, together with juvenile hormone III and 7-octadecen-9-ynoic acid. Lettowienolide and lettowiquinone exhibited mild in vitro activity against the Plasmodium falciparum malaria parasite (each IC(50) approximately 20 microg mL(-1)). Structural determination was achieved based on extensive analysis of spectroscopic data.

Antimosquito and antimicrobial clerodanoids and a chlorobenzenoid from Tessmannia species.

The clerodane diterpenoids trans-kolavenolic acid, 18-oxocleroda-3,13(E)-dien-15-oic acid, ent-(18-hydroxycarbonyl)-cleroda-3,13(E)-dien-15-oate, 2-oxo-ent-cleroda-3,13(Z)-dien-15-oic acid and trans-2-oxo-ent-cleroda-13(Z)-en-15-oic acid, and the chlorobenzenoid O-(3-hydroxy-4-hydroxycarbonyl-5-pentylphenyl)-3-chloro-4-methoxy-6-pentyl-2-oxybenzoic acid were isolated from Tessmannia martiniana var pauloi and T. martiniana var matiniana. Structures were established based on interpretation of spectroscopic data. Some of the compounds exhibited significant antimosquito, antifungal and antibacterial activities.

Aristolactams, 1-(2-C-methyl-beta-D-ribofuranosyl)-uracil and other bioactive constituents of Toussaintia orientalis.

The new aristolactam alkaloid toussalactam {2-hydroxy-1,6-dimethoxy-5H-dibenzo[cdf]indol-4-one} and the known ones, namely aristolactam AII, aristolactam BII, piperolactam C and aristolactam FII; 1-(2-C-methyl-beta-D-ribofuranosyl)-uracil, 3,4,5-trimethoxyphenyl-beta-D-glucopyranoside, and three catechinoids were isolated from the cytotoxic Toussaintia orientalis Verdc stem and root bark extracts, and their structures established based on analysis of spectroscopic data. The aristolactams exhibited antimicrobial and antiinflammatory activity, aristolactam FII showing almost the same level of activity as the standard anti-inflammatory agent Indomethacin. The compounds also exhibited either mild or no antiproliferative and cytotoxic activities, except aristolactam FII that showed the same level of cytotoxicity as the standard drug Camptothecin. 1-(2-C-Methyl-beta-D-ribofuranosyl)-uracil, which is being reported for the first time as a natural product, was inactive in the antibacterial, antifungal, antiinflammatory, antiproliferative and cytotoxicity assays.

Cytotoxic, anti-proliferative and antimicrobial furanoditerpenoids from Stuhlmania moavi.

The furanoditerpenoids voucapane, voucapane-6alpha,7alpha-diol, voucapane-18,19-diol and 18-hydroxyvoucapan-19-al were isolated from the cytotoxic stem and root bark extracts of Stuhlmaniamoavi Verdc. (Ceasalpiniaceae) and their structures established based on analysis of spectroscopic data. The compounds exhibited anti-proliferative, cytotoxic, antibacterial and antifungal activities, 18-hydroxyvoucapan-19-al showing the highest anti-proliferative and cytotoxic properties. Voucapane-18,19-diol was only mildly active but the activity was enhanced for its 18,19-di-(4-methyl)-benzenesulphonate. Some of these results thus corroborate the traditional medicinal uses of the crude extracts for the treatment of skin infections.

Anti-mosquito and antimicrobial nor-halimanoids, isocoumarins and an anilinoid from Tessmannia densiflora.

The nor-halimane diterpenoid tessmannic acid and its methyl, 2-methylisopropyl and 1-methylbutyl esters, the unusual isocoumarins 8-hydroxy-6-methoxy-3-pentylisocoumarin and 7-chloro-8-hydroxy-6-methoxy-3-pentylisocoumarin, and 5-pentyl-3-methoxy-N-butylaniline were isolated from the stem and root bark extracts of Tessmannia densiflora Harms (Caesalpiniaceae) that showed mosquito larvicidal activity. The structures were determined on interpretation of spectroscopic data. Tessmannic acid and its methyl ester exhibited antibacterial and antifungal activity. The compounds also caused high larvae and adult Anopheles gambiae mosquitoe mortality effects, and stronger mosquito repellency than that shown by the standard repellent DEET, hence indicating Tessmannia species to be potential sources of bioactive natural products.

Larvicidal and IGR activity of extract of Tanzanian plants against malaria vector mosquitoes.

BACKGROUND & OBJECTIVES: This paper reports the larvicidal activity of seventeen Tanzanian plant species against the malaria vector, Anopheles gambiae s.s. Giles larvae. Some of the plants are used traditionally as sources of insecticidal materials. METHODS: The crude extracts from the leaves, stem and root barks of the investigated plants were obtained by solvent extraction and then bio-assayed following WHO protocols showed LC50 values 10 to 400 ppm after 24 h exposure. The structures were determined on interpretation of spectroscopic data. RESULTS: The most active extracts were those from the stem and root barks of Annona squamosa, Uvaria faulknerae, U. kirkii and Uvariodendron pycnophyllum, all of which had LC50 values between 10 and 100 ppm. Long-term exposure beyond 24 h also showed more susceptibility of the larvae to the extracts. Larvae deformities by forming tail-like structures were observed for the methanol extracts of Tessmannia martiniana var pauloi. INTERPRETATION & CONCLUSION: The results suggest that the investigated plant extracts are promising as larvicides against An. gambiae s.s. Giles mosquitoes and could be useful leads in the search for new and biodegradable plant derived larvicide products.

Mosquito larvicidal constituents from Lantana viburnoides sp viburnoides var kisi (A. rich) Verdc (Verbenaceae).

BACKGROUND & OBJECTIVES: Lantana viburnoides sp viburnoides var kisi is used in Tanzania ethnobotanically to repel mosquitoes as well as in traditional medicine for stomach ache relief. Bioassay-guided fractionation and subtraction bioassays of the dichloromethane extract of the root barks were carried out in order to identify the bioactive components for controlling Anopheles gambiae s.s. mosquito larvae. METHODS: Twenty late III or early IV instar larvae of An. gambiae s.s. were exposed to various concentrations of the plant extracts, fractions, blends and pure compounds, and were assayed in the laboratory by using the protocol of WHO 1996. Mean mortalities were compared using Dunnett's test (p < 0.05) and lethal concentration calculated by Lackfit Inversel of the SAS programme. RESULTS: The crude extract (LC50 = 7.70 ppm in 72 h) and fractions exhibited different level of mosquito larvicidal activity with subtraction of some fractions resulting in activity enhancement. The active fractions contained furanonaphthaquinones regio-isomers (LC50 = 5.48-5.70 ppm in 72 h) and the lantadene triterpenoid camaric acid (LC50 = 6.19 ppm in 72 h) as active principles while the lupane triterpenoid betulinic acid (LC50 < 10 ppm in 72 h) was obtained from the least active fraction. INTERPRETATION & CONCLUSION: Crude extracts and some fractions had higher or comparable larvicidal activity to the pure compounds. These results demonstrate that L. viburnoides sp viburnoides var kisi extracts may serve as larvicides for managing various mosquito habitats even in their semi-purified form. The isolated compounds can be used as distinct markers in the active extracts or plant materials belonging to the genus Lantana.

Antifungal rosane diterpenes and other constituents of Hugonia castaneifolia.

The rosane diterpenoids hugorosenone [3beta-hydroxyrosa-1(10),15-dien-2-one], 18-hydroxyhugorosenone and 18-hydroxy-3-deoxyhugorosenone, and 12-hydroxy-13-methylpodocarpa-8,11,13-trien-3-one were isolated as antifungal constituents of H. castaneifolia Engl. root bark, together with the previously reported di-podocarpanoids hugonone A and hugonone B that were weakly active, and 1(10),15-rosadiene-2beta,3beta-diol (hugorosenol), 4alpha-methoxyhimachal-10-en-5beta-ol (hugonianene B) and 2-hydroxyhenpentacont-2-enal, and the known compounds tetracosyl-(E)-ferrulate and caryophyllene oxide, all of which were inactive. Hugorosenone also exhibited activity against Anopheles gambiae mosquito larvae. Structural determination was achieved based on spectroscopic data.

A novel antiplasmodial 3',5'-diformylchalcone and other constituents of Friesodielsia obovata.

Phytochemical investigation of the stem and root barks of Friesodielsia obovata Benth (Annonaceae) afforded new 3',5'-diformyl-2',4',6'-trihydroxychalcone and N-formyl-7-hydroxyglaucine together with five known compounds, 3',5'-dimethyl-2',4',6'-trihydroxychalcone, (-)-crotepoxide, demethoxymatteucinol, lawinal, and benzyl benzoate. 3',5'-diformyl-2',4',6'-trihydroxychalcone indicated significant antiplasmodial, cytotoxicity, and larvicidal activities.

A new cytotoxic and larvicidal himachalenoid, rosanoids and other constituents of Hugonia busseana.

A new cytotoxic himachalene sesquiterpenoid 4alpha-methoxy-5,9-oxahimachal-9-ene (hugonianene A) which exhibited moderate activity against Anopheles gambiae mosquito larvae after 24 h at a concentration of 0.237 mg mL(-1), and at 48 h and 72 h contact time causing complete larval mortality up to a concentration as low as 0.01369 mg mL(-1), was isolated as the major constituent of the cytotoxic root bark extract of Hugonia busseana. Hugonianene A was obtained together with the hitherto unreported rosane diterpenoid 18-hydroxyrosane, the known rosane diterpenoid hugorosediol, an inseparable mixture of 12-methoxy-13-methylpodocarpa-8,11,13-trien-3,7-dione and 12-methoxy-13-methylpodocarpa-1,8,11,13-tetraen-3,7-dione, and the di-podocarpanoid hugonone B that was previously obtained from H. castaneifolia.

C18 tetraynoic fatty acids and essential oil composition of Mkilua fragrans.

The fatty acids 17,18-dihydroxyoctadeca-9,11,13,15-tetraynoic acid (mkiluaynoic acid A) and 18-hydroxyoctadeca-9,11,13,15-tetraynoic acid (mkiluaynoic acid B), 5,7,3',4'-tetrahydroxyflavanol, 3,4-dihydroxybenzoic acid and a mixture of stearic and oleic acids were isolated from fruits and stem barks of Mkilua fragrans (Annonaceae). Mkiluaynoic acid A exhibited antifungal activity against Candida albicans comparable with that of the standard antifungal agent Ketoconazole. Structural determination was achieved by analysis of spectroscopic data. The flower stalks yielded essential oils that mainly consisted of sesquiterpenoids as revealed by GC-MS analysis, whereby 14 sesquiterpenes and four other compounds were identified.

Prenylindoles from Tanzanian Monodora and Isolona species.

6-(3-Methyl-but-2-enyl)-1,3-dihydro-indol-2-one, annonidine F [3-[6-(3-methyl-but-2-enyl)-1H-indolyl]-6-(3-methyl-but-2-enyl)-1H-indole], 1H-indole-5-carbaldehyde, 6-(3-methyl-2-butenyl)-1H-indole, 6-(3-methyl-buta-1,3-dienyl)-1H-indole, 6-(4-oxo-but-2-enyl)-1H-indole and 3-geranylindole were isolated from Monodora angolensis (Annonaceae) while 3-(1,1-dimethyl-but-2-enyl)-5-(3-methyl-but-2-enyl)-1H-indole (caulidine A), 4-[3-(1,1-dimethyl-but-2-enyl)-1H-indol-5-yl]-but-3-en-2-one (caulidine B), 5-(3-methyl-2-butenyl)-1H-indole and 5-(3-methylbuta-1,3-dienyl)-1H-indole were obtained from Isolona cauliflora (Annonaceae); structural determination by spectroscopic analysis. Some of the prenylindoles had antifungal and antimalarial activities.

(+/-)-Schefflone: a trimeric monoterpenoid from the root bark of Uvaria scheffleri.

The trimeric monoterpene and mildly mosquito larvicidal agent, (+/-)-schefflone, that is an apparent derivative of the antiparasitic aromatic monoterpene espintanol, was isolated from the antimalarial extracts of the root bark of Uvaria scheffleri, together with espintanol. Structural determination of (+/-)-schefflone was achieved from spectroscopic data and confirmed by single-crystal X-ray diffraction analysis. (+/-)-Schefflone can be considered a product of a non-enzymatic Diels-Alder-type cycloaddition reaction of the quinonemethide derivative of espintanol as the diene and dienophile.

The caulindoles: dimeric prenylindoles from Isolona cauliflora.

Four dimeric prenylindoles occurring in diastereomeric pairs, the caulindole A-D, 5-(3-methyl-2-butenyl)-1H-indole, and (E)-5-(3-methylbuta-1,3-dienyl)-1H-indole were isolated from the stem and root barks of Isolona cauliflora, an ecologically endangered Annonaceae species. Structural determination was achieved based on interpretation of spectroscopic data. Biogenetically, the caulindoles are considered as Diels-Alder-type cycloaddition products of mono- and/or bis-prenylindoles [e.g. 5-(3-methyl-2-butenyl)-1H-indole and (E)-5-(3-methylbuta-1,3-dienyl)-1H-indole] as the dienes and dienophiles.

A novel phenanthrenolide and C-benzyl dihydrochalcones from Uvaria puguensis.

Two new natural products, the phenanthrenoid puguenolide (6-hydroxy-3-methoxy-4-oxapyren-5-one) and isoangoletin were isolated from the stem bark of the newly described Uvaria species, U. puguensis D.M. Johnson, together with the sesquiterpene guaiol and the usual C-benzyldihydrochalcones previously found in the genus Uvaria, viz. uvaretin, diuvaretin, chamuvaritin and a mixture of triuvaretin and isotriuvaretin. Structural elucidation was achieved through a combination of spectroscopic methods.