Antibacterial stigmastane-type steroids and other constituents from the leaves of Vernonia glabra (Steetz) Vatke (Asteraceae).

Two new stigmastane steroids (1 and 2) were isolated from the methanol extract of the leaves of Vernonia glabra, together with seventeen known compounds (3-19) including one fatty acid, four triterpenoids, four steroids, one trinitropropanoyl glucoside, and seven flavonoids. The structures of compounds 1 and 2 were assigned based on their IR, NMR and MS data, and by comparison with literature values. The MeOH extract, its fractions and isolated compounds were subjected to in vitro antibacterial assay against two Gram-positive (Staphylococcus aureus ATCC25923 and Streptococcus pneumoniae ATCC49619) and two Gram-negative (Escherichia coli ATCC8739 and Klebsiella pneumoniae ATCC10031) bacteria, using broth microdilution method. The extract and fractions exhibited (16 ≤ MIC ≤ 512 µg/mL) antibacterial activities. The isolated and tested compounds were also active (16 ≤ MIC ≤ 128 µg/mL) against the four pathogenic bacteria, with compound 2 being the most active and E. coli, the most sensitive microorganism.

Dryoptkirbioside, A New Fructofuranoside Glycerol, and Other Constituents from Dryopteris kirbi Hook et Grav Rhizomes.

A new fructofuranoside glycerol, dryoptkirbioside (1), along with thirteen known compounds (2-14), was isolated from the MeOH extract of Dryopteris kirbi rhizomes by silica gel column chromatography, Sephadex LH-20 column chromatography, and semipreparative HPLC. The structure of the new compound was determined by analyses of its spectroscopic data including nuclear magnetic resonance (NMR), and high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) and chemical conversions. The hexane-soluble portion and the EAFA fraction showed strong activities against lung (A549), breast (MCF-7), and cervical (HeLa) human cancer cell lines (IC50 values ranging from 4.0 to 8.8 µg/mL). Aspidinol P (5) and aspidinol B (6) exhibited moderate to low cytotoxicity on the three cell lines (IC50 values ranging from 20.4 to 58.7 µM). The MeOH extract and hexane-soluble portion had excellent activities against Staphylococcus aureus and Bacillus subtilis (MICs 11.7 and 23.4 µg/mL), whereas the AcOEt- and BuOH-soluble portions were significantly active on S. aureus (MICs 46.9 and 93.8 µg/mL). The main fractions EAFB , EAFC and nBFB displayed excellent activity against S. aureus (MICs 11.7 and 23.4 µg/mL). Aspidinol B (6) had significant activity, while aspidinol P (5) was moderately active against S. aureus and B. subtilis (MICs 42.0 and 89.5 µM).

A New Ceramide from Cissus Aralioides Baker (Vitaceae) and its Antimicrobial Activity.

Purification through repeated column chromatography over silica gel and Sephadex LH-20 of the ethanol extract of the stems of Cissus aralioides (Baker) Planch. resulted in the isolation of a new ceramide, aralioidamide A (1), along with five known compounds (2-6). Their structures were determined by the extensive analyses of their spectroscopic (1D and 2D NMR) and spectrometric data, and comparison with those reported in the literature. Aralioidamide A (1) displayed weak antibacterial activity (MIC=256 µg/mL) against Bacillus subtilis, Staphylococcus aureus and Shigella flexneri and was inactive (MIC>256 µg/mL) against the tested fungi.

Echinograciolide, a new antibacterial nor-triterpenoid and other constituents from Echinops gracilis O. Hoffm. (Asteraceae).

Antibacterial resistance is a serious threat against humankind and the search for new therapeutics is needed. This study aims to investigate the antibacterial activity of extracts and compounds from Echinops gracilis O. Hoffm. Standard chromatographic and spectroscopic methods were used to isolate and characterize compounds (1-15) from the methanol extract. The extract, chromatographic fractions and compounds 1-3, 8, 11, 13 and 14 were subjected to in vitro antibacterial assays against Staphylococcus aureus ATCC25923, Salmonella Typhi ATCC6539, Klebsiella pneumoniae 22, and Salmonella Typhi 68, using broth micro-dilution method. As results, a new nor-triterpenoid (1) and fourteen known compounds (2-15) were characterized. The extract and fractions displayed moderate (128 ≤ MIC ≤ 512 µg/mL) and significant (MIC 64 µg/mL) antibacterial activities. Compounds 1 and 14 showed the best anti-staphylococcal and anti-salmonella activity (MIC 16 µg/mL), respectively. These results partially justified the antimicrobial uses of E. gracilis in traditional medicine.

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.

Cytotoxic potential of dihydrochalcones from Eriosema glomeratum and their semi-synthetic derivatives.

In the search of cytotoxic dihydrochalcones, this investigation led to the isolation of seven compounds (1-7) from Eriosema glomeratum and the preparation of eight derivatives (8-15). The cytotoxicity of samples was evaluated against lung (A549), breast (MCF-7), and cervical (HeLa) human cancer cells. The CH2Cl2/MeOH extract of the aerial part had strong cytotoxicity against all cells [IC50 11.2 (MCF-7), 8.4 (HeLa) and 13.1 (A549) µg/mL]. A strong activity was also displayed by the n-hexane fraction on MCF-7 (IC50 11.2 µg/mL). The precursor 3 and the derivative 8 were specifically found as strong cytotoxic agents toward MCF-7 (7.6 µM) and HeLa (3.1 µM), respectively and were more effective than the positive control. Derivatives 8 (3.1 µM) and 9 (21.3 µM) against HeLa were most potent than their precursor 3 (23.7 µM). This is the first preparation of 8-14 as well as the cytotoxicity of 3, 4, 8-15, fractions, and extract.

A new antimicrobial nor-friedelane-type triterpenoid and other constituents from Plectranthus glandulosus Hook. f. (Lamiaceae).

Chemical investigation of the ethanol extract from the whole plant of Plectranthus glandulosus led to the isolation of a new nor-triterpenoid (1) along with seventeen known compounds (2-18) including seven triterpenoids, nine flavonoids and one steroid. Their structures were established on the basis of 1D- and 2D-NMR, IR, and MS experiments, and by comparison of their spectroscopic data with those of similar compounds reported in the literature. The EtOH extract and some isolated triterpenoids (1-4 and 13) were subjected to in vitro antimicrobial assays against a panel of pathogenic microorganisms, including Gram-positive and Gram-negative bacteria, and fungi using broth microdilution method. The EtOH extract displayed moderate activity (MIC = 512 µg/mL) against Staphylococcus aureus MSSA1, Shigella flexneri SDINT and Cryptococcus neoformans H99. Compounds 1, 4 and 13 showed the most potent antimicrobial effect with MICs of 32-256 µg/mL.

Roeperone A, a new tetraoxygenated xanthone and other compounds from the leaves of Hypericum roeperianum Schimp. (Hypericaceae).

Chemical investigation of the methanol extract from the leaves of H. roeperianum led to the isolation of a new tetraoxygenated xanthone along with eleven known compounds including six xanthones, one polyketide, one flavonoid, one ferulic acid derivative and two pentacyclic triterpenoids. Their structures were established on the basis of 1D- and 2D-NMR, UV, IR, and MS experiments, and by comparison of their spectroscopic data with those of similar compounds reported in the literature. The new xanthone was tested against a panel of eight bacterial strains including six Gram-negative and two Gram-positive bacteria. As results, it exhibited weak antibacterial activity with MIC values ranging from 64 to 128 µg/mL.

Two new triterpenoid fatty acid esters from Schefflera barteri Harms (Araliaceae)§.

Two new fatty acid esters of triterpenoids (1-2) together with eleven known compounds (3-13) were obtained after investigation of the CH2Cl2-MeOH (1:1) crude extract from the leaves of Schefflera barteri Harms. All these compounds (1-13) were isolated for the first time from this plant among which compounds 3, 4, 6 and 9-13 were also isolated from the genus Schefflera for the first time. The structures of the isolated compounds were elucidated by analyses of their spectroscopic data (1D and 2D NMR, and MS). The antibacterial and cytotoxic activities of crude extracts, fractions and compounds (1, 2, 5, 6, 8 and 9) were investigated against both Gram-negative and Gram-positive bacteria strains as well as on human cervix carcinoma and colon adenocarcinoma cancer cell lines, respectively. They showed weak to significant activity towards the strains and malignant cells used.

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).

An Efflux Pumps Inhibitor Significantly Improved the Antibacterial Activity of Botanicals from Plectranthus glandulosus towards MDR Phenotypes.

Bacterial multidrug resistance causes many therapeutic failures, making it more difficult to fight against bacterial diseases. This study aimed to investigate the antibacterial activity of extract, fractions, and phytochemicals from Plectranthus glandulosus (Lamiaceae) against multidrug-resistant (MDR) Gram-negative phenotypes expressing efflux pumps. The crude extract after extraction was subjected to column chromatography, and the structures of the isolated compounds were determined using spectrometric and spectroscopic techniques. Antibacterial assays of samples alone and in the presence of an efflux pump inhibitor (phenylalanine-arginine ß-naphthylamide, PAßN) were carried out using the broth microdilution method. The phytochemical study of P. glandulosus plant extract afforded seven major fractions (A-G) which lead to the isolation of seventeen known compounds. The ethanol extract of P. glandulosus was not active at up to 1024 µg/mL, whereas its fractions showed MICs varying from 32 to 512 µg/mL on the studied bacteria. Fraction C of P. glandulosus showed the lowest MIC (32 µg/mL) on E. coli ATCC8739 strain. Fraction D presented the highest activity spectrum by inhibiting the growth of 90% (9/10) of the studied bacteria. The presence of PAßN has improved the activity of extract and all fractions. Overall, the tested phytochemicals showed low activity against the studied bacteria. The overall results obtained in this study show that some fractions from P. glandulosus, mainly fractions C and D, should be investigated more for their possible use to fight against MDR bacteria.

Saponin with antibacterial activity from the roots of Albizia adianthifolia.

An unprecedented saponin is being reported herein together with five known compounds from the methanol extract of the roots of Albizia adianthifolia. The metabolites were obtained over repeated open column chromatography methods and spectroscopic followed by spectrometric techniques. The isolated compounds were tested against eleven Gram-negative bacteria including multidrug resistant strains. The results revealed considerable inhibition of the new saponin against the studied bacteria with MIC values ranging from 16 to 128 µg/mL.

Antinociceptive, anti-inflammatory and antioxidant effects of Boerhavia coccinea extracts and fractions on acute and persistent inflammatory pain models.

Background Boerhavia coccinea (Nyctaginaceae) is an herbaceous plant used for the treatment of pain. The aim of this study was to evaluate the antinociceptive and anti-inflammatory activities of the aqueous (AEBC) and ethanol (EEBC) extracts of Boerhavia coccinea as well as the major fractions (F1, F2 and F3) from EEBC. Methods The antinociceptive effect of the extracts and fractions was evaluated using formalin test. AEBC, EEBC and F1 were selected and further evaluated acutely (24 h) and chronically (16 days) in Complete Freund's Adjuvant (CFA)-induced persistent inflammatory pain for their antihyperalgesic and anti-inflammatory effects. They were administered orally (100 and 200 mg/kg/day) from 48 h following the intraplantar injection of 100 µL of CFA. After the 16 days of chronic treatment, rats' spinal cord and brain were collected for the evaluation of oxidative stress parameters namely nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT). Results AEBC, EEBC and F1 significantly inhibited the first and second phases of the formalin-induced pain. They significantly reduced the hyperalgesia both in acute and chronic treatments. These extracts showed no acute anti-inflammatory effect. AEBC and EEBC exhibited anti-inflammatory activities after repeated administration. AEBC, EEBC and F1 significantly reduced MDA level and significantly increased SOD and catalase activities, mainly in the spinal cord. AEBC and EEBC also reduced the NO production in the spinal cord. Conclusions Boerhavia coccinea extracts and F1 possess potent antinociceptive activity which is not related to their anti-inflammatory properties. Their antioxidant effects may contribute to these activities in chronic treatment.

New Alkenylresorcinols with Cytotoxic and Antimicrobial Activities from the Leaves of Embelia schimperi.

A phytochemical study of the methanol extract of the leaves of Embelia schimperi resulted in the isolation of three new alkenylresorcinols, 1:  - 3: , together with the known analogs 4:  - 7: . Their structures were established by a combination of spectroscopic techniques. Compounds 1:  - 7: exhibited moderate cytotoxic activity against human cervical cancer cells HeLa-S3 and more pronounced antimicrobial properties towards bacteria and filamentous fungi. The present study falls into an ongoing research project on the characterization of bioactive phenolic lipids from plants of the family Primulaceae.

Antibacterial and antibiotic-modifying activities of fractions and compounds from Albizia adianthifolia against MDR Gram-negative enteric bacteria.

BACKGROUND: Albizia adianthifolia (Schum.) is medicinally used in Cameroon to manage bronchitis and skin diseases. Our previous study documented the antibacterial potential of its roots' methanol extract. In this study, methanol roots extract was subjected to chromatography techniques and fractions (AARa and AARb), sub-fractions (AARa1-4, AARb1-2 and AARb11-14) together with isolated phytochemicals were assessed for their antimicrobial as well as their antibiotic-potentiating effects towards Gram-negative multidrug resistant (MDR) bacteria. METHODS: The antibacterial activities of the samples (determination of Minimal Inhibitory « MIC ¼ and Minimal Bactericidal Concentration « MBC ¼) were determined by the modified rapid p-iodonitrotetrazolium chloride (INT) colorimetric assay, as well as those of antibiotics in association with the compounds. Column chromatography was applied to isolate phytochemicals from roots extract and their chemical structures were determined using spectroscopic techniques. RESULTS: The phytochemicals isolated were stearic acid (1), a mixture (1:1) of stigmasterol and ß-sitosterol (2 +  3), ß-sitosterol 3-O-ß-D-glucopyranoside (4), palmatin (5), homomangiferin (6) and mangiferin (7). Fraction AARa exhibited selective inhibitory effects whilst all tested bacteria were inhibited by AARb in MIC ranges of 8 to 1024 µg/mL. Sub-fractions AARb1-2 had MIC values between 8 µg/mL and 1024 µg/mL on all tested bacteria. Phytochemicals 4, 2 +  3 and 7 inhibited the growth of 54.54% (6/11), 45.45% (5/11) and 27.27% (3/11) tested bacterial strains, respectively. When tested with an efflux pumps inhibitor (Phenylalanine-Arginine-ß-Naphthylamide or PAßN), the inhibitory effects of compounds 2 + 3 and 4 increased towards all the tested bacteria. In association with erythromycin (ERY), streptomycin (STR) and tetracycline (TET), compounds 2 + 3 and 4 had the most significant synergistic activity on the seven selected bacteria. CONCLUSION: The present study provides information on the possible use of Albizia adianthifolia and its constituents in the control of Gram-negative infections including MDR phenotypes.

Cardenolides and dihydro-ß-agarofuran sesquiterpenes from the seeds of Salacia staudtiana.

Phytochemical studies of the seeds of the Cameroonian medicinal plant, Salacia staudtiana, resulted in the isolation and identification of five new cardenolides (1-5) as well as a new dihydro-ß-agarofuran (9), along with eight known compounds. The structures of all compounds were elucidated by 1D/2D NMR, ESI-HRMS data and comparison with literature data. The relative configurations of the new compounds were defined by X-ray crystallography analysis, NOESY correlations and coupling constants. We evaluated their antibacterial efficacy against two commonly dispersed environmental strains of Escherichia coli and Bacillus subtilis, and two pathogenic strains of Staphylococcus aureus and Pseudomonas aeruginosa, compared to the standard antibiotics, streptomycin and gentamicin. Moreover, we assessed the antibacterial activity of the crude extract of the seeds in parallel to evaluate the plausible synergistic effects of the compounds in chemical defense of the seeds during germination and plant reproduction. The isolated compounds showed moderate antibacterial activities against the tested organisms. Compounds 1 and 3 and the crude extract exhibited distinct antibacterial activities against B. subtilis and S. aureus. The isolated compounds showed weak DPPH radical scavenging properties compared to the reference standard (Trolox). Our study lends evidence to the antibacterial chemical defense of S. staudtiana seeds by seed-borne compounds.

Antimicrobial and antioxidant activities of triterpenoid and phenolic derivatives from two Cameroonian Melastomataceae plants: Dissotis senegambiensis and Amphiblemma monticola.

BACKGROUND: Antimicrobial resistance is a serious threat against humankind and the search for new therapeutics is needed. This study aims to investigate the antimicrobial and antioxidant activities of ethanol extracts and compounds isolated from Dissotis senegambiensis and Amphiblemma monticola, two Cameroonian Melastomataceae species traditionally used for the treatment of fever, malaria and infectious diseases. METHODS: The plant extracts were prepared by maceration in ethanol. Standard chromatographic and spectroscopic methods were used to isolate and identify fourteen compounds from the two plant species [1-6 (from D. senegambiensis), 3, 4 and 7-14 (from A. monticola)]. A two-fold serial micro-dilution method was used to determine the minimum inhibitory concentration (MIC) against four bacterial strains including two resistant bacterial strains, methicillin resistant S. aureus (MRSA3) and methicillin resistant S. aureus (MRSA4) and three yeast strains. RESULTS: The fractionation of EtOH extracts afforded fourteen compounds belonging to triterpenoid and phenolic derivatives. The ethanol extracts, compounds 3, 5-8, 10 and the mixture of 10 + 12 were active against all the tested bacterial and fungal species. Compound 7 (MIC = 16-32 µg/mL) and 10 (MIC = 8-16 µg/mL) displayed the largest antibacterial and antifungal activities, respectively. Compounds 7, 10 and the mixture of 10 + 12 showed prominent antibacterial activity against methicillin- resistant S. aureus (MRSA) which is in some cases equal to that of ciprofloxacin used as reference antibacterial drug. Compound 8 also showed high radical-scavenging activities and ferric reducing power when compared with vitamin C and butylated hydroxytoluene used as reference antioxidants. The tested samples were non-toxic to normal cells highlighting their good selectivity. CONCLUSIONS: The result of this investigation reveals the potential of D. senegambiensis and A. monticola as well as the most active compounds in the search for new antimicrobial and antioxidant agents. So, further investigations are needed.

Cardenolides from the stem bark of Salacia staudtiana.

Seven new cardenolides, staudtianoside A-F (1-6) and staudtianogenin A (8), were isolated along with six known compounds from the stem bark of the Cameroonian medicinal plant Salacia staudtiana Loes. ex Fritsch. The structures were elucidated by means of ESI-HRMS and NMR spectroscopic methods and by comparison with literature data. The relative configurations of the new compounds were determined by X-ray diffraction analysis, NOESY correlation and coupling constants. We evaluated the antibacterial efficacy of the isolated compounds against two commonly dispersed environmental strains of Escherichia coli and Bacillus subtilis, as well as against two human pathogenic clinical strains of Staphylococcus aureus and Pseudomonas aeruginosa. Compounds 1, 2 and 8 exhibited marked antibacterial potencies against the clinically relevant P. aeruginosa that were comparable to the standard antibiotics. Compound 2 was also active against S. aureus and E. coli. Further, compounds 5 and 8 demonstrated efficacy against E. coli as well as B. subtilis. The structure-activity relationship of the tested compounds is discussed.

Three New Abietane-Type Diterpenoids from Plectranthus africanus and Their Antibacterial Activities.

Three new abietane-type diterpenoids, plectranthroyleanones A - C (1:  - 3: ), together with five known compounds (4:  - 8: ) were isolated from the methanol extract of the whole plant of Plectranthus africanus using column chromatography techniques. The structures of the new compounds were elucidated using a combination of 1D and 2D NMR and HRESIMS analyses. Compound 1: exhibited weak activities with minimal inhibitory concentration values of 75 µg/mL against gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus, and 150 µg/mL against two gram-negative bacteria, Pseudomonas aeruginosa and Klebsiella pneumoniae, respectively, while 2: and 3: had moderate antibacterial activity against K. pneumoniae with a minimal inhibitory concentration value of 37.5 µg/mL.