Two new flavone glycosides from the leaves of Ochna afzelii Oliv. (Ochnaceae).

Two new glycosylflavones, 6''-O-acetyl-8-C-ß-D-galactopyranosylchrysoeriol (1) and 8-C-ß-D-galactopyranosylchrysoeriol (2) were isolated from the methanol extract of the leaves of Ochna afzelii Oliv., along with four known compounds namely 8-C-ß-D-galactopyranosylapigenin (3), ochnaflavone (4), sitosterol-3-O-ß-D-glucopyranoside (5) and D-mannitol (6). Isolation was performed chromatographically and the structures of the purified compounds were elucidated by analyzing their spectroscopic and mass spectrometric data. The antibacterial activity of extract, fractions, and compounds 1 - 4 was evaluated using broth microdilution method against Gram-positive and Gram-negative bacteria while the antioxidant capacity was performed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the ferric reducing antioxidant power (FRAP) methods. The new flavones (1 and 2) displayed moderate antibacterial activities (MIC = 32 - 64 µg/mL) and weak antioxidant properties.

Alkenylbenzoquinones and other compounds from the fruit of Maesa lanceolata exhibited potent cytotoxic, antibacterial, and antiradical scavenging activities§.

A phytochemical study of the methanol extract of the fruit of Maesa lanceolata resulted in the isolation of a new alkenylbenzoquinone (1), alongside the known compounds (Z)-2,5-dihydroxy-6-methyl-3-(pentadec-10'-enyl)-1,4-benzoquinone (2), 2,5-dihydroxy-6-methyl-3-(nonadec-14'-enyl)-1,4-benzoquinone (3), 2,5-dihydroxy-6-methyl-3-(tridecyl)-1,4-benzoquinone (4), (2S,3S,4R,2'R,9E)-[2'-hydroxytetraeicosanoyl]-2-aminooctadec-9-ene-1,3,4-triol (5), monopalmitin (glyceryl palmitate) (6), lupeol (7), and 3-O-(ß-D-glucopyranoside)-ß-sitosterol (8). The structures of the compounds were established by the means of spectroscopic (1 D- and 2 D-NMR) and spectrometric techniques (MS). The isolated compounds were assessed for their antibacterial, cytotoxic, and antiradical activities. Compound 2 showed moderate activity against Staphylococcus warneri (DSMZ 20036), while the other compounds were inactive. The two quinones 1 and 2 were significantly cytotoxic, with IC50 values of 0.005 µM and 12.5 µM respectively, and were weakly active towards DPPH radical (IC50 >250 µg/mL).

Prenylated Flavonoids and C-15 Isoprenoid Analogues with Antibacterial Properties from the Whole Plant of Imperata cylindrica (L.) Raeusch (Gramineae).

The local botanical Imperata cylindrica in Cameroon was investigated for its antibacterial potency. The methanol extract afforded a total of seven compounds, including five hitherto unreported compounds comprising three flavonoids (1-3) and two C-15 isoprenoid analogues (4 and 5) together with known derivatives (6 and 7). The novelty of the flavonoids was related to the presence of both methyl and prenyl groups. The potential origin of the methyl in the flavonoids is discussed, as well as the chemophenetic significance of our findings. Isolation was performed over repeated silica gel and Sephadex LH-20 column chromatography and the structures were elucidated by (NMR and MS). The crude methanol extract and isolated compounds showed considerable antibacterial potency against a panel of multi-drug resistant (MDR) bacterial strains. The best MIC values were obtained with compound (2) against S. aureus ATCC 25923 (32 µg/mL) and MRSA1 (16 µg/mL).

Antiparasitic Constituents of Beilschmiedia louisii and Beilschmiedia obscura and Some Semisynthetic Derivatives (Lauraceae).

The MeOH/CH2Cl2 (1:1) extracts of the roots and leaves of Beilschmiedia louisii and B. obscura showed potent antitrypanosomal activity during preliminary screening on Trypanosoma brucei brucei. Phytochemical investigation of these extracts led to the isolation of a mixture of two new endiandric acid derivatives beilschmiedol B (1) and beilschmiedol C (2), and one new phenylalkene obscurene A (3) together with twelve known compounds (4-15). In addition, four new derivatives (11a-11d) were synthesized from compound 11. Their structures were elucidated based on their NMR and MS data. Compounds 5, 6, and 7 were isolated for the first time from the Beilschmiedia genus. Additionally, the NMR data of compound 4 are given here for the first time. The isolates were evaluated for their antitrypanosomal and antimalarial activities against Tb brucei and the Plasmodium falciparum chloroquine-resistant strain Pf3D7 in vitro, respectively. From the tested compounds, the mixture of new compounds 1 and 2 exhibited the most potent antitrypanosomal activity in vitro with IC50 value of 4.91 µM.

Synthesis, Urease Inhibition and Molecular Modelling Studies of Novel Derivatives of the Naturally Occurring ß-Amyrenone.

Urease enzyme (UE) has been reported to be a potent virulence factor for Helicobacter pylori (HP) bacteria indicated to be responsible for various gastrointestinal diseases. Therefore, the spread of HP, currently regarded by the World Health Organization as a class 1 carcinogen, could be better controlled by targeting UE. It is in this line that we have synthesized three new derivatives (2-4) of the naturally occurring olean-12-en-3-one (1), which was previously isolated from the figs of Ficus vallis-choudae Delile (Moraceae). Among the synthesized compounds, 3 and 4 contain an indole moiety. Their structures were unambiguously assigned by spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The starting material and the synthesized compounds were screened for UE inhibition activity, and showed significant activities with IC50 values ranging from 14.5 to 24.6 µM, with compound (1) being the most potent as compared to the positive control thiourea (IC50 = 21.6 µM). Amongst the synthetic derivatives, compound 4 was the most potent (IC50 = 17.9 µM), while the others showed activities close to that of the control. In addition, molecular docking study of target compounds 2-4 was performed in an attempt to explore their binding mode for the design of more potent UE inhibitors.

Antiplasmodial Properties and Cytotoxicity of Endophytic Fungi from Symphonia globulifera (Clusiaceae).

There is continuing need for new and improved drugs to tackle malaria, which remains a major public health problem, especially in tropical and subtropical regions of the world. Natural products represent credible sources of new antiplasmodial agents for antimalarial drug development. Endophytes that widely colonize healthy tissues of plants have been shown to synthesize a great variety of secondary metabolites that might possess antiplasmodial benefits. The present study was carried out to evaluate the antiplasmodial potential of extracts from endophytic fungi isolated from Symphonia globulifera against a chloroquine-resistant strain of Plasmodium falciparum (PfINDO). Sixty-one fungal isolates with infection frequency of 67.77% were obtained from the bark of S. globulifera. Twelve selected isolates were classified into six different genera including Fusarium, Paecilomyces, Penicillium, Aspergillus, Mucor, and Bipolaris. Extracts from the 12 isolates were tested against PfINDO, and nine showed good activity (IC50 < 10 μg·mL−1) with three fungi including Paecilomyces lilacinus (IC50 = 0.44 μg·mL−1), Penicillium janthinellum (IC50 = 0.2 μg·mL−1), and Paecilomyces sp. (IC50 = 0.55 μg·mL−1) showing the highest promise. These three isolates were found to be less cytotoxic against the HEK293T cell line with selectivity indices ranging from 24.52 to 70.56. Results from this study indicate that endophytic fungi from Symphonia globulifera are promising sources of hit compounds that might be further investigated as novel drugs against malaria. The chemical investigation of active extracts is ongoing.

Crystal and mol-ecular structure of aflatrem.

The crystal structure of the title compound, C32H39NO4, confirms the absolute configuration of the seven chiral centres in the mol-ecule. The molecule has a 1,1-dimethylprop-2-enyl substituent on the indole nucleus and this nucleus shares one edge with the five-membered ring which is, in turn, connected to a sequence of three edge-shared fused rings. The skeleton is completed by the 7,7-trimethyl-6,8-dioxabi-cyclo-[3.2.1]oct-3-en-2-one group connected to the terminal cyclohexene ring. The two cyclohexane rings adopt chair and half-chair conformations, while in the dioxabi-cyclo-[3.2.1]oct-3-en-2-one unit, the six-membered ring has a half-chair conformation. The indole system of the mol-ecule exhibits a tilt of 2.02 (1)° between its two rings. In the crystal, O-H⋯O hydrogen bonds connect mol-ecules into chains along [010]. Weak N-H⋯π inter-actions connect these chains, forming sheets parallel to (10-1).

Crystal structure of obscurine: a natural product isolated from the stem bark of B. obscura.

The title compound, C24H31NO3 {systematic name: (E)-3-[(1R*,2S*,4aS*,8aR*)-2-(benzo[d][1,3]dioxol-5-yl)-1,2,4a,5,6,7,8,8a-octa-hydro-naphthalen-1-yl]-N-iso-butyl-acryl-amide}, is a natural product isolated from the stem bark of B. obscura. It is composed of an octa-hydro-naphthalene ring system substituted with an essentially planar benzodioxole ring system [r.m.s. deviation = 0.012 Å] and an extended iso-butyl-acryl-amide group. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds, forming chains propagating along [100]. The chains are linked by pairs of C-H⋯O hydrogen bonds, involving inversion-related benzodioxole ring systems, forming ribbons lying parallel to (010). There are also C-H⋯π inter-actions present within the ribbons.

Antiplasmodial sesquiterpenes from the seeds of Salacia longipes var. camerunensis.

Phytochemical investigation of the seeds of Salacia longipes var. camerunensis led to the isolation of four sesquiterpenoid derivatives, salaterpene A (1) (1α,2ß,8ß-triacetoxy-6ß,9ß-dibenzoyloxy-4ß-hydroxy-dihydro-ß-agarofuran), salaterpene B (2) (1α,2ß,8ß-triacetoxy-9ß-benzoyloxy-6ß-cinnamoyloxy-4ß-hydroxy-dihydro-ß-agarofuran), salaterpene C (3) (1α,2ß-diacetoxy-6ß,9ß-dibenzoyloxy-4ß-hydroxy-dihydro-ß-agarofuran) and salaterpene D (4) (2ß-acetoxy-1α,6ß-dibenzoyloxy-4ß-hydroxy-9ß-nicotinoyloxy-dihydro-ß-agarofuran) together with two known compounds (5 and 6). The structures of the compounds were established by means of NMR spectroscopy. Compounds 1-4 and 6 were tested in vitro for their antiplasmodial activity against Plasmodium falciparum chloroquine-resistant strain W2. All the tested compounds exhibited a moderate potency with IC50 below 2.7 µM.

Compounds from Sorindeia juglandifolia (Anacardiaceae) exhibit potent anti-plasmodial activities in vitro and in vivo.

BACKGROUND: Discovering new lead compounds against malaria parasites is a crucial step to ensuring a sustainable global pipeline for effective anti-malarial drugs. As far as we know, no previous phytochemical or pharmacological investigations have been carried out on Sorindeia juglandifolia. This paper describes the results of an anti-malarial activity-driven investigation of the fruits of this Cameroonian plant. METHODS: Air-dried fruits were extracted by maceration using methanol. The extract was fractionated by flash chromatography followed by column chromatography over silica gel, eluting with gradients of hexane-ethyl acetate mixtures. Resulting fractions and compounds were tested in vitro against the Plasmodium falciparum chloroquine-resistant strain W2, against field isolates of P. falciparum, and against the P. falciparum recombinant cysteine protease falcipain-2. Promising fractions were assessed for acute toxicity after oral administration in mice. One of the promising isolated compounds was assessed in vivo against the rodent malaria parasite Plasmodium berghei. RESULTS: The main end-products of the activity-guided fractionation were 2,3,6-trihydroxy benzoic acid (1) and 2,3,6-trihydroxy methyl benzoate (2). Overall, nine fractions tested against P. falciparum W2 and falcipain-2 were active, with IC50 values of 2.3-11.6 µg/ml for W2, and 1.1-21.9 µg/ml for falcipain-2. Purified compounds (1) and (2) also showed inhibitory effects against P. falciparum W2 (IC50s 16.5 µM and 13.0 µM) and falcipain-2 (IC50s 35.4 and 6.1 µM). In studies of P. falciparum isolates from Cameroon, the plant fractions demonstrated IC50 values of 0.14-19.4 µg/ml and compounds (1) and (2) values of 6.3 and 36.1 µM. In vivo assessment of compound (1) showed activity against P. berghei strain B, with mean parasitaemia suppressive dose and curative dose of 44.9 mg/kg and 42.2 mg/kg, respectively. Active fractions were found to be safe in mice after oral administration of 7 g/kg body weight. CONCLUSIONS: Fractions of Sorindeia juglandifolia and two compounds isolated from these fractions were active against cultured malaria parasites, the P. falciparum protease falcipain-2, and in a rodent malaria model. These results suggest that further investigation of the anti-malarial activities of natural products from S. juglandifolia will be appropriate.

Isoflavone dimers and other bioactive constituents from the figs of Ficus mucuso.

Phytochemical investigation of the figs of Ficus mucuso led to the isolation of three new isoflavone dimer derivatives, mucusisoflavones A-C (1-3), together with 16 known compounds. Some of the isolates were tested in vitro for their inhibitory properties toward ß-glucuronidase and Plasmodium falciparum enoyl-ACP reductase (PfENR) enzymes. Compound 1 (IC50) 0.68 µM) showed inhibitory activity on ß-glucuronidase enzyme, while 3 (IC50) 7.69 µM) exhibited a weak inhibitory activity against P. falciparum enoyl-ACP reductase (PfENR).

Bioactive steroidal alkaloids from Sarcococca hookeriana.

Four new 5 alpha-pregnane-type steroidal alkaloids, hookerianamides L(1), M(2), N(3), and O(4), and a known N-formylchonemorphine (5) have been isolated by acid-base extraction of the dichloromethane extract of Sarcococca hookeriana. The structures of all compounds were determined with spectroscopic techniques and by comparison with literature data. All compounds displayed antileishmanial and antibacterial properties. Compounds 1, 4, and 5 were found to be more potent than standard pentamidine (IC (50) = 9.59 microg/mL) with respect to leishmanicidal activity. The minimum inhibitory concentration of most of the compounds against Bacillus subtilis, Streptococcus minor, and Streptococcus ferus was lower than that of the standard ampicillin.

Bioactive 5alpha-pregnane-type steroidal alkaloids from Sarcococca hookeriana.

The bioassay-guided phytochemical investigation of Sarcococca hookeriana with respect to cholinesterase inhibitory properties has yielded two new 5alpha-pregnane-type steroidal alkaloids, hookerianamides J (1) and K (2), along with eight known compounds (3-10). The structures of 1 and 2 were elucidated by spectroscopic methods. These compounds displayed good to moderate activities in vitro against the enzymes acetylcholinesterase (IC 50 8.1-48.5 microM) and butyrylcholinesterase (IC 50 0.4-4.0 microM). Compounds 1-10 were also tested in vitro for their leishmanicidal activity against Leishmania major and for their antibacterial activities against Bacillus subtilis, Micrococcus luteus, Streptococcus faecalis, and Pseudomonas pallida.

Terpenoid alkaloids of the Buxaceae family with potential biological importance.

The plants of the family Buxaceae are widely used in traditional medicine and constitute rich sources of terpenoidal alkaloids. Compounds of this family have been the subject of numerous chemical and pharmacological studies over past decades because of their interesting biological activities such as cholinesterase inhibition, as well as antibacterial and antileishmanial activities. The chemical and biological properties of these alkaloids, including data relevant to straightforward structure determination and information on biosynthesis, are highlighted in this review, with 144 references being cited.

Anthraquinones from the stem bark of Stereospermum zenkeri with antimicrobial activity.

Two anthraquinones, zenkequinones A and B were isolated from the stem bark of Stereospermum zenkeri together with known sterequinone-F, p-coumaric acid, sitosterol-3-O-beta-D-glucopyranoside and 3beta-hydroxyolean-12-en-28-O-beta-D-glucopyranoside. Their structures were established by spectroscopic methods. The antimicrobial activity of the isolated compounds was evaluated against six multiresistant strains of pathogens. Zenkequinone B showed the best antibacterial activity (MIC 9.50 microg/ml) against gram-negative Pseudomonas aeruginosa.

Xanthones and other constituents of Allanblackia monticola (Guttiferae).

A xanthone derivative, 3,6,7-trihydroxy-1-methoxyxanthone has been isolated from the stem bark of Allanblackia monticola together with other known compounds, 2,6-dihydroxy-1-methoxyxanthone, allanxanthone A, epicathechin and oleanolic acid acetate. The structure of the new compound was elucidated by spectroscopic methods.