Design, synthesis, characterization, and anticancer activity of a novel series of O-substituted chalcone derivatives.

A new series of O-substituted chalcone derivatives bearing an/a allyl-, prenyl- or propargyl-substituent at different positions of rings A and B and their derivatives as drug leads, was designed, synthesized, and characterized. The chalcone derivatives were synthesized via base catalyzed Claisen-Schmidt condensation in MeOH or EtOH solutions of appropriately substituted aromatic ketones with O-allyl, and O-propargylvanillin, respectively. The intermediates O-substituted phenylketone derivatives were firstly synthesized by nucleophilic substitution reaction. All the newly synthesized compounds were characterized by IR, NMR spectral data and elemental analyses. A preliminary cytotoxicity was performed with the compounds (1a, 1b, 2a, 2b, 3a, 3b, 4a, 5a-f, 6a-d, 7a-d) and the positive control, doxorubicin towards CCRF-CEM leukemia cells. Amongst them, compounds 1a, 2a, 5b-d, 6b, 7a, 7c and doxorubicin displayed IC50 values below 20 µM while other compounds were less or not active at up to 50 µM. Remarkably interesting cytotoxic effects, with IC50 values below 1 µM were recorded with 5c against HCT116 p53-/- colon adenocarcinoma cells, 5e against CCRF-CEM cells and MDA-MB-231-BCRP breast adenocarcinoma cells, and 6b against HCT116 p53+/+ cells and HCT116 p53-/- cells.

Induction of mitochondrial dependent apoptosis and cell cycle arrest in human promyelocytic leukemia HL-60 cells by an extract from Dorstenia psilurus: a spice from Cameroon.

BACKGROUND: The use of edible plants is an integral part of dietary behavior in the West region of Cameroon. Dorstenia psilurus (Moraceae) is widely used as spice and as medicinal plant for the treatment of several diseases in Cameroon. The aim of this study is to investigate the cytotoxic and apoptotic potential of methanol extract of D. psilurus in human promyelocytic leukemia (HL-60) cells and prostate cancer (PC-3) cells. METHODS: Cytotoxicity of D. psilurus extract was tested in HL-60 and PC-3 cells using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay and flow cytometric methods RESULTS: The methanol extract of D. psilurus have significant in vitro cytotoxic activity in HL-60 cells and PC-3 cells with IC50 value of 12 ± 1.54 µg/ml and 18 ± 0.45 µg/ml respectively after 48 h. The mechanism of antiproliferative activity showed that after 24 h, D. psilurus extract induces apoptosis on HL-60 cells by the generation of reactive oxygen species (ROS) along with concurrent loss of mitochondrial membrane potential, modification in the DNA distribution and enhance of G2/M phase cell cycle. CONCLUSION: The extract induces apoptosis of HL-60 cells associated with ROS production, loss of mitochondrial membrane potential and apoptotic DNA fragmentation.

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.

Antimicrobial activities of the methanol extract and compounds from the twigs of Dorstenia mannii (Moraceae).

BACKGROUND: Dorstenia mannii (Moraceae) is a medicinal herb used traditionally for the treatment of many diseases. In the present study, the methanol extract of D. mannii and nine of its isolated compounds, namely dorsmanin A (1), B (2), C (3), D (4), E (6), F (7), G (8) dorsmanin I (9) and 6,8-diprenyleriodictyol (5), were tested for their antimicrobial activities against yeast, Mycobacteria and Gram-negative bacteria. METHODS: The microplate alamar blue assay (MABA) and the broth microdilution method were used to determine the minimal inhibitory concentration (MIC) and minimal microbicidal concentration (MMC) of the above extract and compounds on a panel of bacterial species. RESULTS: The results of the MIC determinations demonstrated that the methanol extract as well as compounds 3 and 8 were able to prevent the growth of all the fourteen studied microorganisms within the concentration range of 4 to 1024 µg/ml. The lowest MIC value for the methanol extract (64 µg/ml) was obtained on Candida albicans. The lowest value for individual compounds (4 µg/ml) was recorded with compounds 3 on Pseudomonas aeruginosa PA01 and 7 on Eschericia coli ATCC strain. The MIC values recorded with compounds 3 on P. aeruginosa PA01, 6 on C. albicans,7 on P. aeruginosa PA01 and K. pneumoniae ATCC strain and C. albicans,and 8 on P. aeruginosa PA01, PA124, P. stuartii, M. tuberculosis MTCS1 were lower than or equal to those of the reference drugs. MMC values not greater than 1024 µg/ml were recorded on all studied microorganisms with compounds 3 and 8. CONCLUSION: The overall results of the present investigation provided evidence that the crude extract of D. mannii as well as some of its compounds such compounds 3 and 8 could be a potential source of natural antimicrobial products.

Antibacterial and antibiotic-potentiation activity of the constituents from aerial part of Donella welwitshii (Sapotaceae) against multidrug resistant phenotypes.

BACKGROUND: The rise of multidrug-resistant (MDR) bacteria is a real public health problem worldwide and is responsible for the increase in hospital infections. Donella welwitschii is a liana or shrub belonging to the family Sapotaceae and traditionally used to cure coughs. OBJECTIVE: This study was conducted with the objective to validate the medicinal properties of this plant, the aerial part was studied for its phytochemical composition using column and PTLC chromatography and exploring its antibacterial and antibiotic-modifying activity as well as those of its phytochemicals. METHODS: The structures of the compounds were elucidated from their physical and spectroscopic data in conjunction with literature. The antibacterial activity of the isolated metabolites was performed toward a panel of MDR Gram negative and Gram-positive bacteria. The broth micro-dilution method was used to determine antibacterial activities, efflux pump effect using the efflux pump inhibitor (EPI) (phenylalanine-arginine-ß-naphthylamide (PAßN)), as well as the modulating activity of antibiotics. Monitoring the acidification of the bacterial growth medium was used to study the effects of the samples on the bacterial proton-ATPase pumps and cellular ATP production. RESULTS: Eleven compounds were isolated including pentacyclic triterpenes, C-glucosyl benzophenones. With a MIC value < 10 µg/mL, diospyric acid (7) significantly inhibited the growth of Escherichia coli AG102, Enterobacter aerogenes ATCC13048, Klebsiella pneumoniae KP55, Providencia stuartii NEA16 and Staphylococcus aureus MRSA3. 28-hydroxy-ß-amyrin (8) significantly impaired the growth of Enterobacter aerogenes EA27, Klebsiella pneumoniae ATCC11296 and Staphylococcus aureus MRSA6; and oleanolic acid (9) strongly impaired the growth of Escherichia coli AG 102, Enterobacter aerogenes EA27 and Providencia stuartii PS2636. Diospyric acid (7) and 28-hydroxy-ß-amyrin (8) induced perturbation of H+-ATPase pump and inhibition of the cellular ATP production. Moreover, at MIC/2 and MIC/4, compounds 7, 8, and 9 strongly improved the antibacterial activity of norfloxacin, ciprofloxacin and doxycycline with antibiotic-modulating factors ranging between 2 and 64. CONCLUSION: The overall results of the current work demonstrate that diospyric acid (7), 28-hydroxy-ß-amyrin (8) and oleanolic acid (9) are the major bioactive constituents of Donella welwitschia towards Gram-negative bacteria expressing MDR phenotypes.

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].

Cytotoxicity and mode of action of four naturally occuring flavonoids from the genus Dorstenia: gancaonin Q, 4-hydroxylonchocarpin, 6-prenylapigenin, and 6,8-diprenyleriodictyol.

Several flavonoid-like compounds were found to possess good antiproliferative properties. Herein, we examined the ability of four naturally occuring and biologically active flavonoids from the genus Dorstenia, gancaonin Q (1), 6-prenylapigenin (2), 6,8-diprenyleriodictyol (3), and 4-hydroxylonchocarpin ( 4), to inhibit the proliferation of a panel of fourteen cancer cell lines including leukemia and solid cancer cells, as well as AML12 normal hepatocytes. The study was extended to the analysis of cell cycle distribution, apoptosis induction, and caspase 3/7 activity and the antiangiogenic properties of the four compounds. The results of the cytotoxicity assays showed that more than 50 % inhibition of proliferation was obtained with compound 1 on all the fourteen studied cancer cell lines, with IC (50) values below 20 µg/mL. Compounds 2, 4, and 3 showed selective activity, with IC (50) values below 20 µg/mL being noted on 57.15 %, 71.42 %, and 85.71 % of the fourteen cancer cell lines, respectively. None of the compounds exhibited more than 50 % inhibition against AML12 normal hepatocytes cells at 20 µg/mL. IC (50) values below or around 4 µg/mL were recorded on 28.57 % of the tested cell lines for both compound 1 and 4 and 21.43 % for compound 3, which appeared to be the best cytotoxic compounds. This study indicates that caspase 3/7 activation is one of the modes of induction of apoptosis for compounds 1, 3, and 4 in CCRF-CEM cells. The results of the antiangiogenic assay indicated that compounds 1, 3, and 4 were also able to inhibit the growth of blood capillaries on the chorioallantoic membrane of quail eggs, the best effect being noted for compound 4 (54.1 % inhibition). The results of the present work provide evidence of the cytotoxic potential of the four studied flavonoids and supportive data for further investigations.

Antimicrobial activities of the methanol extract, fractions and compounds from Ficus polita Vahl. (Moraceae).

BACKGROUND: Many plants of the family Moraceae are used in the treatment of infectious diseases. Ficus polita Vahl., an edible plant belonging to this family is used traditionally in case of dyspepsia, infectious diseases, abdominal pains and diarrhea. The present work was designed to assess the antimicrobial activity of the methanol extract from the roots of F. polita (FPR), as well as that of its fractions (FPR1-5) and two of the eight isolated compounds, namely euphol-3-O-cinnamate (1) and (E)-3,5,4'-trihydroxy-stilbene-3,5-O-ß-D-diglucopyranoside (8). METHODS: The liquid microdilution assay was used in the determination of the minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC), against seven bacterial and one fungal species. RESULTS: The results of the MIC determination showed that the crude extract, fractions FPR1, FPR2 and compound 8 were able to prevent the growth of the eight tested microorganisms. Other samples showed selective activity. The lowest MIC value of 64 µg/ml for the crude extract was recorded on 50% of the studied microbial species. The corresponding value for fractions of 32 µg/ml was obtained on Salmonella typhi, Escherichia coli and Candida albicans ATCC strains. The MIC values recorded with compound 8 on the resistant Pseudomonas aeruginosa PA01 strain was equal to that of chloramphenicol used as reference antibiotic. CONCLUSION: The obtained results highlighted the interesting antimicrobial potency of F. polita as well as that of compound 8, and provided scientific basis for the traditional use of this taxon in the treatment of microbial infections.

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.

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.

Identification of 3,3'-O-dimethylellagic acid and apigenin as the main antiplasmodial constituents of Endodesmia calophylloides Benth and Hymenostegia afzelii (Oliver.) Harms.

BACKGROUND: Endodesmia calophylloides and Hymenostegia afzelii belong to the Guttiferae and Caesalpiniaceae plant families with known uses in African ethno-medicine to treat malaria and several other diseases. This study aimed at identifying antiplasmodial natural products from selected crude extracts from H. afzelii and E. calophylloides and to assess their cytotoxicity. METHODS: The extracts from H. afzelii and E. calophylloides were subjected to bioassay-guided fractionation to identify antiplasmodial compounds. The hydroethanol and methanol stem bark crude extracts, fractions and isolated compounds were assessed for antiplasmodial activity against the chloroquine-sensitive 3D7 and multi-drug resistant Dd2 strains of Plasmodium falciparum using the SYBR green I fluorescence-based microdilution assay. Cytotoxicity of active extracts, fractions and compounds was determined on African green monkey normal kidney Vero and murine macrophage Raw 264.7 cell lines using the Resazurin-based viability assay. RESULTS: The hydroethanolic extract of H. afzelii stem bark (HasbHE) and the methanolic extract of E. calophylloides stem bark (EcsbM) exhibited the highest potency against both Pf3D7 (EC50 values of 3.32 ± 0.15 µg/mL and 7.40 ± 0.19 µg/mL, respectively) and PfDd2 (EC50 of 3.08 ± 0.21 µg/mL and 7.48 ± 0.07 µg/mL, respectively) strains. Both extracts showed high selectivity toward Plasmodium parasites (SI > 13). The biological activity-guided fractionation led to the identification of five compounds (Compounds 1-5) from HasbHE and one compound (Compound 6) from EcsbM. Of these, Compound 1 corresponding to apigenin (EC50 Pf3D7, of 19.01 ± 0.72 µM and EC50 PfDd2 of 16.39 ± 0.52 µM), and Compound 6 corresponding to 3,3'-O-dimethylellagic acid (EC50 Pf3D7 of 4.27 ± 0.05 µM and EC50 PfDd2 of 1.36 ± 0.47 µM) displayed the highest antiplasmodial activities. Interestingly, both compounds exhibited negligible cytotoxicity against both Vero and Raw 264.7 cell lines with selectivity indices greater than 9. CONCLUSIONS: This study led to the identification of two potent antiplasmodial natural compounds, 3,3'-O-dimethylellagic acid and apigenin that could serve as starting points for further antimalarial drug discovery.

Efflux pumps are involved in the defense of Gram-negative bacteria against the natural products isobavachalcone and diospyrone.

The activities of two naturally occurring compounds, isobavachalcone and diospyrone, against documented strains and multidrug-resistant (MDR) Gram-negative bacterial isolates were evaluated. The results indicated that the two compounds exhibited intrinsic antibacterial activity against several Gram-negative bacteria, and their activities were significantly improved in the presence of an efflux pump inhibitor (MIC values decreased to below 10 microg/ml). In addition, the activities of isobavachalcone and diospyrone against various strains exhibiting deletions of the major efflux pump components (AcrAB, TolC) were significantly increased. The overall results indicate that isobavachalcone and diospyrone could be candidates for the development of new drugs against MDR strains and that their use in combination with efflux pump inhibitors reinforces their activity.

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.

Trypanocidal and leishmanicidal activity of six limonoids.

Six limonoids [kotschyienone A and B (1, 2), 7-deacetylgedunin (3), 7-deacetyl-7-oxogedunin (4), andirobin (5) and methyl angolensate (6)] were investigated for their trypanocidal and leishmanicidal activities using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. Whereas all compounds showed anti-trypanosomal activity, only compounds 1-4 displayed anti-leishmanial activity. The 50% growth inhibition (GI50) values for the trypanocidal and leishmanicidal activity of the compounds ranged between 2.5 and 14.9 µM. Kotschyienone A (1) was found to be the most active compound with a minimal inhibition concentration (MIC) value of 10 µM and GI50 values between 2.5 and 2.9 µM. Only compounds 1 and 3 showed moderate cytotoxicity against HL-60 cells with MIC and GI50 values of 100 µM and 31.5-46.2 µM, respectively. Compound 1 was also found to show activity against intracellular amastigotes of L. major with a GI50 value of 1.5 µM. The results suggest that limonoids have potential as drug candidates for the development of new treatments against trypanosomiasis and leishmaniasis.

Antistaphylococcal Activity of Extracts, Fractions, and Compounds of Acacia polyacantha Wild (Fabaceae).

Acacia polyacantha is a medicinal plant traditionally used to treat livestock diseases and gastrointestinal infections; our study was undertaken to evaluate the antistaphylococcal activities of the methanolic leaf, bark, and root extracts, fractions, and compounds from Acacia polyacantha against a panel of 14 multidrug-resistant Staphylococcus bacterial strains overexpressing efflux pumps. The study was also extended to investigate two possible modes of action, that is, influence on bacterial growth kinetics and influence on proton-ATPase pumps, of the most active compound against a reference strain. Materials and Methods. The crude extracts after extraction were subjected to column chromatography. Antibacterial assays of extracts, fractions, and compounds alone and in the presence of efflux pump inhibitors were carried out using the broth microdilution method and the study of two mechanisms of action achieved by standard methods with the most active compound. Results. The phytochemical study of Acacia polyacantha leaves leads to the isolation of stigmasterol (1), ß-amyrin (2), 3-O-methyl-D-chiro-inositol (3), epicatechin (4), quercetin-3-O-galactoside (5), 3-O-[ß-D-xylopyranosyl-(1 ⟶ 4)-ß-D-galactopyranosyl]-oleanolic acid (6), 3-O-[ß-galactopyranosyl-(1⟶ 4)-ß-D-galactopyranosyl]-oleanolic acid (7) and that of leaves lead to the isolation of lupeol (8) 2,3-dihydroxypropyltetracosanoate (9), and methyl-gallate (10). Leaf, root, and bark extracts inhibited 92.85% (13/14), 92.85% (13/14), and 71.43 % (10/14) of the tested bacteria strains, respectively, with minimum inhibitory concentration (MIC) varying between 16 and 1024 µg/mL. Fractions exhibited better activities compared to those of their extracts of origin, as their MICs ranged from 16 to 512 µg/mL, with fractions from leaves being more active than those obtained from barks. Compounds had varying activities; MICs varied from 16 to 512 µg/mL with compound 4 presenting the best activity as MICs ≤100 µg/mL were obtained against 11 of the tested bacteria. The activities of extracts, fractions, and compounds were improved in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP) as an efflux pump inhibitor to as much as >128 folds. Meanwhile, in the presence of chlorpromazine as an efflux pump inhibitor, only the activity of compound 10 was improved on 10 of the tested bacteria strains. Compound 4 prolonged the lag phase of the growth kinetic in a concentration-dependent manner and equally inhibited the proton-ATPase pumps of the tested bacteria strains. Conclusion. The present study demonstrates the antistaphylococcal potential of Acacia polyacantha and its constituents to combat bacterial infections alone or in combination with efflux pump inhibitors.

Antibacterial and Antibiotic Modifying Potential of Crude Extracts, Fractions, and Compounds from Acacia polyacantha Willd. against MDR Gram-Negative Bacteria.

The present study aimed to assess the in vitro antibacterial and antibiotic modifying activities of methanol extracts prepared from the leaf (APL) and bark (APB) of Acacia polyacantha, fractions (APLa-d) and compounds isolated from APL against a panel of multidrug resistant (MDR) Gram-negative bacteria. Leaf extract was subjected to column chromatography for compounds isolation; antibacterial assays were performed on samples alone and with an efflux pump inhibitor (EPI), respectively, and several antibiotics on the tested bacteria. The phytochemical investigation of APL led to the isolation of stigmasterol (1), ß-amyrin (2), 3-O-ß-D-glucopyranosylstigmasterol (3), 3-O-methyl-D-chiro-inositol (4), epicatechin (5), quercetin-3-O-glucoside (6), 3-O-[ß-D-xylopyranosyl-(1→4)-ß-D-galactopyranosyl]-oleanolic acid (7), and 3-O-[ß-galactopyranosyl-(1→4)-ß-D-galactopyranosyl]-oleanolic acid (8). APL and APB had minimal inhibitory concentration (MIC) values ≤ 1024 µg/mL on 73.3% and 46.7% of the tested bacteria, respectively. APLb and APLd were effective against 88.9% of tested bacterial species with compound 8 showing the highest activity inhibiting 88.9% of tested bacteria. The EPI, phenylalanine-arginine-ß-naphthylamide (PAßN), strongly improved the activity of APL, APLb, APLd, and compound 8 on all tested bacteria. Synergistic effects were obtained when APL and compounds 7 and 8 were combined with erythromycin (ERY), gentamycin (GEN), ciprofloxacin (CIP), and norfloxacin (NOR). The present study demonstrates the antibacterial potential of Acacia polyacantha and its constituents to combat bacterial infections alone or in combination with EPI.

Polyacanthoside A, a new oleanane-type triterpenoid saponin with cytotoxic effects from the leaves of Acacia polyacantha (Fabaceae).

The chemical investigation of the leaves and stem bark of Acacia polyacantha (Fabaceae) led to the isolation of a new oleanane-type triterpenoid saponin named polyacanthoside A 1 together with fifteen known compounds. Their structures were established from spectral , mainly HRESIMS, 1D NMR and 2D NMR and by comparison with literature data. The cytotoxicity of compound 1 and the analogues 8 as well as doxorubicin was determined in a panel of 9 cancer cell lines including sensitive and drug resistant phenotypes. Unlike the analogue 8, compound 1 as well as doxorubicin displayed cytotoxic effects in all the 9 tested cancer cell lines with IC50 values ranged from 8.90 µM (towards CCRF-CEM leukemia cells) to 35.21 µM (towards HepG2 hepatocarcinoma cells) for compound 1 and from 0.02 µM (towards CCRF-CEM leukemia cells) to 66.83 µM (against CEM/ADR5000 leukemia cells) for doxorubicin.

Antimicrobial activity of the crude extracts and five flavonoids from the twigs of Dorstenia barteri (Moraceae).

The aim of this study was to evaluate the antimicrobial activity of the crude extract of the twigs of Dorstenia barteri (DBT) as well as that of four of the five flavonoids isolated from this extract. Gram-positive bacteria (six species), Gram-negative bacteria (12 species) and fungi (four species) were used. The agar disc diffusion test was used to determine the sensitivity of the tested samples while the well micro-dilution was used to determine the minimal inhibition concentrations (MIC) and the minimal microbicidal concentration (MMC) of the active samples. The results of the disc diffusion assay showed that DBT, isobavachalcone (1), and kanzonol C (4) prevented the growth of all the 22 tested microbial species. Other compounds showed selective activity. The inhibitory activity of the most active compounds namely compounds 1 and 4 was noted on 86.4% of the tested microorganisms and that of 4-hydroxylonchocarpin (3) was observed on 72.7%. This lowest MIC value of 19.06microg/ml was observed with the crude extract on seven microorganisms namely Citrobacter freundii, Enterobacter aerogens, Proteus mirabilis, Proteus vulgaris, Bacillus megaterium, Bacillus stearothermophilus and Candida albicans. For the tested compounds, the lowest MIC value of 0.3microg/ml (on six of the 22 organisms tested) was obtained only with compound 1, which appeared as the most active compound. This lowest MIC value (0.3microg/ml) is about 4-fold lower than that of the RA, indicating the powerful and very interesting antimicrobial potential of isobavachalcone (1). The antimicrobial activities of DBT, as well as that of compounds 1, 3, 4, amentoflavone (5) are being reported for the first time. The overall results provide promising baseline information for the potential use of the crude extracts from DBT as well as some of the isolated compounds in the treatment of bacterial and fungal infections.

Antimicrobial activity of the methanolic extracts and compounds from Treculia obovoidea (Moraceae).

The crude extract from Treculia obovoidea was subjected to purification by repeated chromatography. Eight compounds were isolated from Treculia obovoidea and identified as Psoralen (1), Bergapten (2), 7-methoxycoumarin (3), 7-hydroxycoumarin (4), 4,2',4'-trihydroxychalcone (5), 4,2',4'-trihydroxy-3-prenylchalcone (6), 3-hydroxy-4-methoxybenzoic acid (7) and O-[3-(2,2-dimethyl-3-oxo-2H-furan-5-yl) butyl] bergaptol (8). These compounds together with the extract were tested for their antimicrobial activity against Gram-positive bacteria (six species), Gram-negative bacteria (12 species) and three Candida species using micro-dilution methods for the determination of the minimal inhibition concentration (MIC) and the minimal microbicidal concentration (MMC). The MIC values obtained with the crude extracts varied from 78.12 to 156.25 microg/ml against 17 (80.95%) of the 21 tested microorganisms. All the isolated compounds showed selective activity. The antimicrobial activity of this plant as well as that of compounds 6 and 8 is being reported for the first time. The obtained results provide promising baseline information for the potential use of these crude extract as well as some of the isolated compounds in the treatment of bacterial and fungal infections.

Antimicrobial activity of the methanolic extract, fractions and four flavonoids from the twigs of Dorstenia angusticornis Engl. (Moraceae).

The methanolic extract (DAT), fractions (FRS) and four flavonoids, namely Gancaonin Q (1), Stipulin (2), Angusticornin B (3) and Bartericin A (4), isolated from the twigs of Dorstenia angusticornis (Moraceae), were tested for their in vitro antimicrobial activity. A total of 22 microbial cultures belonging to three Candida species, 6 Gram-positive and 13 Gram-negative bacterial species were used in this study. The inhibition zones (IZ) of the test samples against the pathogens were determined by the Agar Hole Diffusion test while the Liquid dilution method was used to determine their minimal inhibition concentrations (MIC) and their minimal microbicidal concentrations (MMC). Results indicate that DAT, compounds 3 and 4 inhibited the growth of all test pathogens. DAT, FRS 3-6, compounds 3 and 4 were both antibacterial and anticandidal. A single-dose oral toxicity performed in accordance with the OPPTS 870.1100 and OECD 401guideline showed that DAT was not toxic. Our findings provide a possible basis for the potential use of twigs from Dorstenia angusticornis in the treatment of infectious diseases.