Soyauxinine, a New Indolopyridoquinazoline Alkaloid from the Stem Bark of Araliopsis soyauxii Engl. (Rutaceae).

The chemical investigation of the total alkaloid extract (TAE) of the stem bark of Araliopsis soyauxii (Rutaceae) afforded an unreported indolopyridoquinazoline (compound 1) along with nine previously known alkaloids 2-10. In addition, six semi-synthetic derivatives 3a-c, 4b, 5a and 6a were prepared by allylation and acetonidation of soyauxinium nitrate (5), edulinine (3), ribalinine (4) and arborinine (6). The structures and spectroscopic data of five of them are reported herein for the first time. The suggested mechanism for the formation of the new N-allylindolopyridoquinazoline 5a is presented. The structures of natural and derived compounds were determined employing extensive NMR and MS techniques. The absolute configuration of stereogenic centers in compounds 2-4 were determined using NOESY technique and confirmed by the single-crystal X-ray diffraction (SC-XRD) technique. The use of SC-XRD further enabled us to carry out a structural revision of soyauxinium chloride recently isolated from the same plant to soyauxinium nitrate (5). The TAE, fractions, compounds 1-7 and 9, and semi-synthetic derivatives 3a-c, 4b, 5a and 6a were evaluated for their cytotoxic activity towards the cervix carcinoma cell line KB-3-1. No significant activity was recorded for most of the compounds except for 9, which showed moderate activity against the tested cancer cell lines.

Chemical Constituents of Macaranga occidentalis, Antimicrobial and Chemophenetic Studies.

Medicinal plants are known as sources of potential antimicrobial compounds belonging to different classes. The aim of the present work was to evaluate the antimicrobial potential of the crude extract, fractions, and some isolated secondary metabolites from the leaves of Macaranga occidentalis, a Cameroonian medicinal plant traditionally used for the treatment of microbial infections. Repeated column chromatography of the ethyl acetate and n-butanol fractions led to the isolation of seventeen previously known compounds (1-17), among which three steroids (1-3), one triterpene (4), four flavonoids (5-8), two stilbenoids (9 and 10) four ellagic acid derivatives (11-14), one geraniinic acid derivative (15), one coumarine (16), and one glyceride (17). Their structures were elucidated mainly by means of extensive spectroscopic and spectrometric (1D and 2D NMR and, MS) analysis and comparison with the published data. The crude extract, fractions, and isolated compounds were all screened for their antimicrobial activity. None of the natural compounds was active against Candida strains. However, the crude extract, fractions, and compounds showed varying levels of antibacterial properties against at least one of the tested bacterial strains, with minimal inhibitory concentrations (MICs) ranging from 250 to 1000 µg/mL. The n-butanol (n-BuOH) fraction was the most active against Escherichia coli ATCC 25922, with an MIC value of 250 µg/mL. Among the isolated compounds, schweinfurthin B (10) exhibited the best activity against Staphylococcus aureus NR 46003 with a MIC value of 62.5 µg/mL. In addition, schweinfurthin O (9) and isomacarangin (6) also exhibited moderate activity against the same strain with a MIC value of 125 µg/mL. Therefore, pharmacomodulation was performed on compound 6 and three new semisynthetic derivatives (6a-c) were prepared by allylation and acetylation reactions and screened for their in vitro antimicrobial activity. None of the semisynthetic derivatives showed antimicrobial activity against the same tested strains. The chemophenetic significance of the isolated compounds is also discussed in this paper.

Flavonoids and triterpenes from Combretum fragrans with anti-inflammatory, antioxidant and antidiabetic potential.

Despite the well-documented benefits of Combretum fragrans in Cameroon, only few scientific works have been done on it. In this study we isolated eight compounds from the leaves extract of C. fragrans: velutin (1), belamcanidin (2), cirsilineol (3), cirsimaritin (4), 3ß-acetoxy-20,24-epoxy-11,25-hydroxy-dammarane (5), combretin A (6), combretin B (7) and a mixture of arjunolic acid (8a) and asiatic acid (8b). Compounds 6 and 7 presented potent anti-inflammatory, antioxidant and antidiabetic activities. Compounds 1, 3, 5 and the mixture of 8a and 8b were significantly active, and compounds 2 and 4 presented moderate activity for reactive oxygen species inhibitory and free-radical scavenging. All compounds were isolated using chromatographic techniques; their structures were elucidated by spectroscopic techniques and their spectroscopic data compared with those of the literature. Anti-inflammatory activity was evaluated via the oxidative burst assay using a luminol-amplified chemiluminescence technique, antioxidant activity by free-radical scavenging activity (DPPH) and antidiabetic activity via α-glucosidase inhibition. All of the isolated compounds (1-8) were reported to exhibit significant antioxidant activity. Compounds 1, 3, and 5-8 exhibited potent chemiluminescence inhibition effect, and only compounds 6 and 7 inhibited α-glucosidase. Thus, C. fragrans can be used as an effective natural source of anti-inflammatory, antioxidant and antidiabetic compounds.

New triterpene saponins from the roots of Acacia macrostachya (Mimosaceae).

Four new oleanane-type saponins, macrostachyaosides A, B, C, and D (1-4) were isolated from the roots of Acacia macrostachya. Their structures were elucidated on the basis of extensive 1D- and 2D-NMR data and HR-ESI-MS analyses. At concentrations of 100 µM of each compounds, none of the tested compounds caused a significant growth reduction against HL60 cells.

Piptadenin, a Novel 3,4-Secooleanane Triterpene and Piptadenamide, a New Ceramide from the Stem Bark of Piptadeniastrum africanum (Hook.f.) Brenan.

Piptadenin (1), a new triterpene along with piptadenamide (10), a new ceramide, have been isolated from the AcOEt-soluble fraction of the MeOH extract of the stem bark of Piptadeniastrum africanum along with nine known compounds, 1-O-[(3ß,22ß)-3,22-dihydroxy-28-oxoolean-12-en-28-yl]-ß-d-glucopyranose (2), 22ß-hydroxyoleanic acid (3), oleanic acid (4), lupeol (5), betulinic acid (6), 5α-stigmasta-7,22-dien-3ß-ol (7), 5α-stigmasta-7,22-dien-3-one (8), (3ß)-stigmast-5-en-3-yl ß-d-glucopyranoside (9) and 2,3-dihydroxypropyl hexacosanoate (11). Except for compound 11, all the isolated compounds are reported for the first time from this plant. The structures of the isolated compounds were elucidated by spectroscopic data including 1D and 2D NMR. The pure compounds 1 - 11 were subjected to the pharmacological screening and compounds 2, 5 - 7 and 9 exhibited potent urease inhibitory activity with IC50 value of 25.8, 28.9, 30.1, 31.8 and 32.7 µm, respectively, whereas compound 1 showed moderate activity (IC50 = 98.7 µm). The potent urease inhibitory activity supplemented the previous literature reports and medicinal uses of this plant.

Two new 5-deoxyflavan-3,4-diol glucosides from roots of Albizia chevalieri.

Phytochemical investigation of the roots of Albizia chevalieri led to the isolation of two new 5-deoxyflavan-3,4-diol glucosides from roots of A. chevalieri, Chevalieriflavanosides A and B. Their structures were established by 2D NMR techniques, UV, IR, CD, and mass spectrometry. Cytotoxicity of the two compounds was evaluated against acute promyelocytic leukemia HL60 cells. The antibacterial activities of 1 and 2 also were evaluated against Pseudomonas aeruginosa and Staphylococcus aureus using the agar diffusion test. Copyright © 2016 John Wiley & Sons, Ltd.

Isolation and antibacterial activity of anomanol B and other secondary metabolites from the stem bark of Anonidium mannii (Annonaceae).

A new Lanosta-7,9(11),22-trien-3,15,20-triol named Anomanol B 1, together with five known compounds: manniindole 2, arborinine 3, polycarpol 4, 8,9-dimethoxyphenanthridin-6(5H)-one 5 and 3-O-ß-D-glucopyranosyl-ß-sitosterol 6 were isolated from the stem bark extract of Anonidium mannii by routine chromatography techniques. 8,9-dimethoxyphenanthridin-6(5H)-one 5, was reported from natural origin for the first time. The structures of the compounds were established by comprehensive elucidation of spectroscopic data and by comparison with literature data. Evaluation of the isolates on Gram-negative bacteria such as Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Providencia stuartii, and Pseudomonas aeruginosa showed that, compound 1 had weak antibacterial activity with minimal inhibitory concentrations (MIC) varying from 128 to 256 µg/mL. Compounds 3, 5, and 6 exhibited moderate to weak activity with MIC of 32 to 128 µg/mL and 64 to 256 µg/mL compared to the reference drug chloramphenicol which inhibited the growth of all studied bacteria with MIC values of 16 to 64 µg/mL.

Atricephenols A and B, two phenolic compounds from Indigofera atriceps Hook.f. (Fabaceae).

The phytochemical investigation of a previously unstudied species of the genus Indigofera, I. atriceps Hook.f. was undertaken and two new phenolic compounds, atricephenols A (1) and B (2) were isolated, along with nine known secondary metabolites viz., (-)-melilotocarpan D (3), genistein (4), melilotocarpan A (5), maackiain (6), p-hydroxybenzaldehyde (7), bornesitol (8), ß-sitosterol (9), sitosterol-3-O-ß-D-glucopyranoside (10) and stigmasterol-3-O-ß-D-glucopyranoside (11). Their structures were elucidated by extensive NMR spectroscopic analyses and HRESIMS, and by comparing their data with those reported in the literature. Compounds 1, 4, 7-11 were tested for their antibacterial efficacies and for their potential to inhibit the enzyme urease. Compounds 7 and 9 showed significant antibacterial activity against Salmonella typhi (ZOIs of 13 and 15 mm, respectively), while the best urease inhibition was measured for compound 9 with an IC50 value of 18.6 µM, which is higher than that of the potent inhibitor, thiourea (IC50 = 21.5 µM).

New lignan glycosides from Justicia secunda Vahl (Acanthaceae) with antimicrobial and antiparasitic properties.

Three new lignan glucosides, namely, justisecundosides A (1), B (2a), and C (2b), were isolated from the whole plant of Justicia secunda together with seven known compounds (3-9). Their structures were established based on a comprehensive analysis of HR-ESI-MS, IR, UV, and CD, in conjunction with their 1D and 2D-NMR data. A putative biogenetic pathway of compounds 1-2a,b from coniferyl alcohol was proposed. In addition, the antimicrobialactivities of the extract, fractions, and some isolated compounds were assessed against multiresistant bacterial and fungal strains. Furthermore, the antiplasmodial, antileishmanial, and antitrypanosomal activities were assessed against the sensitive (3D7) and multidrug-resistant (Dd2) strains of P. falciparum, promastigote and bloodstream forms of L. donovani, and Trypanosoma brucei, respectively. Compound 4 exhibited moderate antibacterial activity against Staphylococcus aureus SA RN 46003 with a MIC value of 62.5 µg/mL. Besides, compound 6 demonstrated a very good activity against sensitive (IC50Pf3D7: 0.81 µg/mL) and multidrug-resistant (IC50PfDd2: 14.61 µg/mL) strains of P. falciparum while compound 4 displayed good antitrypanosomal activity (IC50: 1.19 µg/mL). Also, compound 1 was the most active on the promastigote form of L. donovani with an IC50 of 13.02 µg/mL.

New antimicrobial cyclolignan and others constituents from the leaves of Scyphocephalium mannii (Benth. & Hook.f.) Warb.

Chemical investigation of the MeOH extract of the leaves of Scyphocephalium mannii (Benth. & Hook.f.) Warb. (Myristicaceae) led to the isolation and characterization of one new metabolite (+)-(7'S, 8S, 8'S)-4,4'-dihydroxy-3,3',5,5'-tetramethoxy-2,7'-cyclolignan (1) along with five known compounds. Their structures were elucidated by spectroscopic means, including 1 D and 2 D NMR, HRESI-MS and by comparison with published data. The absolute configuration of compound 1 was determined by single-crystal X-RAY diffraction. Compound 1 showed moderate antifungal activity against Cryptococcus neoformans with respective MIC and MMC values of 64 and 256 µg/mL.

Chemical constituents of two Cameroonian medicinal plants: Sida rhombifolia L. and Sida acuta Burm. f. (Malvaceae) and their antiplasmodial activity.

An extensive phytochemical investigation of the EtOH/H2O (7:3) extracts of Sida rhombifolia L. and Sida acuta Burm. f., yielded a previously undescribed ceramide named rhombifoliamide (1) and a xylitol dimer (2), naturally isolated here for the first time, as well as the thirteen known compounds viz, oleanolic acid (3), ß-amyrin glucoside (4), ursolic acid (5), ß-sitosterol glucoside (6), tiliroside (7), 1,6-dihydroxyxanthone (8), a mixture of stigmasterol (9) and ß-sitosterol (10), cryptolepine (11), 20-Hydroxyecdysone (12), (E)-suberenol (13), thamnosmonin (14) and xanthyletin (15). Their structures were elucidated by the analyses of their spectroscopic and spectrometric data (1 D and 2 D NMR, and HRESI-MS) and by comparison with the previously reported data. The crude extracts, fractions, and some isolated compounds were tested against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum strains. All the tested samples demonstrated moderate and/or significant activities against 3D7 (IC50 values: 0.18-20.11 µg/mL) and Dd2 (IC50 values: 0.74-63.09 µg/mL).[Formula: see text].

O-prenylated acridone alkaloids from the stems of Balsamocitrus paniculata (Rutaceae).

Two new O-prenylated acridone alkaloids, balsacridone A (1) and B (2), together with eighteen known compounds were isolated from the methanol extract from the stems of Balsamocitrus paniculata, a Cameroonian medicinal plant. The structures of all compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (EI and ESI) data, and chemical reactions. N-methyl-6-methoxybenzoxazolinone (16) was isolated for the first time from a natural source while compounds 13, 14, and 15 for the first time from this genus. Pure compounds were tested for their activity against bacteria, fungi, and plant pathogen oomycetes, using the paper disk agar diffusion assay. The agar diffusion test delivered low to missing antimicrobial activities, corresponding to MICs > 1 mg/mL. However, compounds 1-15 exhibited a strong suppressive effect on phagocytosis response upon activation with serum opsonized zymosan in the range of IC50 = 0.5-7.2 µM, and the acridone alkaloids (1-5), N-trans-p-coumaroyltyramine (13), and N-trans-pcoumaroyloctopamine (14) displayed weak cytotoxic activity against the human Caucasian prostate adenocarcinoma cell line PC-3, with IC50 values ranging from 69.8 to 99.0 µM.

Phenol esters and other constituents from the stem barks of Stereospermum acuminatissimum.

A new ester, 2-(4'-hydroxyphenyl)ethyl dotriacontanoate (1), and a new inseparable mixture of octacosan-1,28-dioldiferulate and triacontan-1,30-dioldiferulate (2) were isolated from the stem barks of Stereospermum acuminatissimum, along with 24 known compounds including 4 triterpenoids, 11 anthraquinones, 2 lignans, 3 phenylpropanoids, 2 4-hydroxyphenethyl esters, 1 methoxyphenol, and 1 iridoid. The structures of the new metabolites were determined with the help of spectroscopic data including extensive 2D NMR spectroscopy. The known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature. The compounds were tested against Candida albicans ATCC 24433, C. albicans ATCC 90028, Candida glabrata ATCC 90030, Candida krusei ATCC 6258, and Candida parapsilosis ATCC 22019. Some of them were moderately active.

A New Ceramide Isolated from Ficus lutea Vahl (Moraceae).

In addition to benjaminamide (2), ß-amyrin, ß-amyrin acetate, lupeol, betulinic acid, ß-sitosterol glucoside, a new ceramide glycoside was isolated from the woods of Ficus lutea Vahl (Moraceae). Using mass fragmentation pattern, 1 and 2D NMR spectra and by comparison with published data, the new compound was characterized as 1-O-ß-D-glucopyranosyl-(2S,3R,5E,12E)-2N-[(2'R)-hydroxyhexadecanoyl]-octadecasphinga-5,12-dienine (1a) for which the trivial name lutaoside was proposed. Some isolated compounds were evaluated for their antimicrobial activities. Compounds 1a and 2 showed some antimicrobial activity.

Triterpene saponins from the roots of Acacia senegal (L.) Willd.

Six new triterpenoid saponins, named senegalosides A-F (1-6) were isolated from the seedpods and roots of Acacia senegal (Mimosaceae). Their structures were elucidated using 1D and 2D-NMR spectroscopic analysis and mass spectrometry. Compound 1 possesses an unusual sapogenin, 3ß-hydroxy-21-oxo-olean-12-en-28-oic acid (machaeric acid), and was reported here in its natural form for the first time within the genus Acacia. Senegaloside A is the first example of a machaeric-type triterpenoid glycoside in the plant kingdom. The cytotoxic effect of isolated saponins was evaluated on the H4IIE rat hepatoma cell line. As a result, compounds 1, 3-6 were not significantly cytotoxic to H4IIE cells even at 200 µM. Compound 2 was suppressed cell viability at 50-200 µM.

A phenanthridin-6(5H)-one derivative and a lanostane-type triterpene with antibacterial properties from Anonidium mannii (Oliv). Engl. & Diels (Annonaceae).

The chemical investigation of Anonidium mannii root extract by column chromatography techniques led to the isolation of eight compounds among which two previously unreported compounds; a lanostane-type triterpene, lanosta-7,9(11),23-triene-3ß,15α-diol 1 and an alkaloid, 9-hydroxy-8-methoxyphenanthridin-6(5H)-one 2 along with six known compounds: lanosta-7,9(11),24-triene-3ß,21-diol 3, oxoanolobine 4, 3, 4-dihydroxybenzoic acid 5, stigmasterol 6, ß-sitosterol 7 and 3-O-ß-D-glucopyranosyl-ß-stigmasterol 8. Their structures were established from spectral data, mainly HR-ESIMS, 1 D and 2 D NMR and by comparison with literature data. The crude root and stem bark extracts (AMR and AMB) and the isolated compounds (1-8) were tested against nine Gram-negative bacteria using rapid p-iodonitrotetrazolium chloride ≥97% (INT) microdilution technique. It was found that AMR, AMB and compound 5 were active against the nine tested bacteria with MIC values ranging from 64 to 1024 µg/mL. Compounds 1-4 had selective antibacterial activities whilst 6-8 were not active.

Bruceadysentoside A, a new pregnane glycoside and others secondary metabolites with cytotoxic activity from brucea antidysenterica J. F. Mill. (simaroubaceae).

The chemical investigation of the root barks leaves and stem barks of Brucea antidysenterica J. F. Mill. (Simaroubaceae) led to the isolation of a new pregnane glycoside, named Bruceadysentoside A or 3-O-ß-L-arabinopyranosyl-pregn-5-en-20-one (1) together with seventeen known compounds. Their structures were established from spectral data, mainly HRESIMS, 1 D and 2 D NMR and by comparison with literature data. Compounds 1, 2, 5, 6, 8, 10, 12 and 13 were tested in vitro for their effects on the viability of two different human cancer cell lines, namely prostate PC-3 adenocarcinoma cells and colorectal HT-29 adenocarcinoma cells. No substantial activities were recorded for 2, 10, 12 and 13 (up to 10 µM concentration). 1, 5 and 8 did not show strong anti-proliferative effects up to 100 µM, however, 6 exhibited a stronger anti-proliferative effect with IC50 values of ∼ 100 µM against PC-3 and ∼ 200 µM against HT-29.

Synthesis of Novel Stilbene-Coumarin Derivatives and Antifungal Screening of Monotes kerstingii-Specialized Metabolites Against Fusarium oxysporum.

Fusarium is one of the most toxigenic phytopathogens causing diseases and reduced agricultural productivity worldwide. Current chemical fungicides exhibit toxicity against non-target organisms, triggering negative environmental impact, and are a danger to consumers. In order to explore the chemical diversity of plants for potential antifungal applications, crude extract and fractions from Monotes kerstingii were screened for their activity against two multi-resistant Fusarium oxysporum strains: Fo32931 and Fo4287. Antifungal activity was evaluated by the determination of minimum inhibitory concentration (MIC) by broth dilution of fermentative yeasts using kinetic OD600 nm reading by a spectrophotometer. The n-butanol fraction showed the best activity against Fo4287. We screened eleven previously reported natural compounds isolated from different fractions, and a stilbene-coumarin 5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-4,7-dimethoxy-3-methyl-2H-1-benzopyran-2-one (1) was the most active compound against both strains. Compound 1 was employed as a nucleophile with a selection of electrophilic derivatizing agents to synthesize five novel stilbene-coumarin analogues. These semisynthetic derivatives showed moderate activity against Fo32931 with only prenylated derivative exhibiting activity comparable to the natural stilbene-coumarin (1), demonstrating the key role of the phenolic group.

Antimicrobial pentacyclic triterpenoids from Terminalia superba.

Antibacterial bioassay-guided fractionation of the methanol extract of the stem bark of Terminalia superba led to the isolation of four new triterpene glucosides (1-4) which were characterized as 2 alpha,3 beta-dihydroxyolean-12-en-28-oic acid 28-O-beta-D-glucopyranoside (1), 2 alpha,3 beta, 21 beta-trihydroxyolean-12-en-28-oic acid 28-O-beta-D-glucopyranoside (2), 2 alpha,3 beta, 29-trihydroxyolean-12-en-28-oic acid 28-O-beta-D-glucopyranoside (3) and 2 alpha,3 beta,23,27-tetrahydroxyolean-12-en-28-oic acid 28-O-beta-D-glucopyranoside (4) together with the known triterpene 2 alpha,3 beta,23-trihydroxyolean-12-en-28-oic acid (5). Structures were established by spectroscopic methods including one- and two-dimensional NMR, EI-MS and HR-EI-MS. The antibacterial activity of 1-5 was also investigated against two gram-positive (Bacillus subtilis, Staphylococcus aureus), and four gram-negative (Escherichia coli, Shigella flexenari, Pseudomonas aeruginosa, Salmonella typhi) bacterial strains.