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].

LC-ToF-ESI-MS Patterns of Hirsutinolide-like Sesquiterpenoids Present in the Elephantopus mollis Kunth Extract and Chemophenetic Significance of Its Chemical Constituents.

A total of nine sesquiterpenoid lactones together with phenolic compounds and other terpenes were identified from the crude methanol extract of Elephantopus mollis Kunth. Compounds were isolated using different chromatographic techniques and their structures were determined by NMR and IR spectroscopy as well as mass spectrometry. The structures of some detected compounds were assigned based on LC-ToF-ESI-MS screening of main fractions/subfractions from flash chromatography and comparison with isolated analogues as standards. The findings revealed not only the in-source loss of water as the base peak in hirsutinolides but also the in-source loss of corresponding alcohol when the oxygen at position 1 is alkylated. The present study also draws up a complement of data with respect to hirsutinolide-like sesquiterpene lactones whose LC-MS characteristics are not available in the literature. The chemophenetic significance is also discussed. Some of the isolated compounds were reported for the first time to be found in the species, the genus as well as the plant family. The medium-polar fractions of the crude extract, also containing the larger amount of sesquiterpenoid lactones, exhibited activity both against a cancer cell line and bacterial strains. Isolated lactones were also active against the cancer cell line, while the chlorogenic derivatives also valuable in Elephantopus genus showed potent radical scavenging activity. This is the first report of cytotoxic and antibacterial activities of our samples against the tested strains and cell line. The present study follows the ongoing research project dealing with the characterization of taxa with antibacterial and antiparasitic activities from Cameroonian pharmacopeia.

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.

Neo-clerodane diterpenoids from Conyza pyrrhopappa Sch.Bip. ex A.Rich.

Two hitherto unknown neo-clerodane-type diterpenoids along with twelve known compounds have been isolated from Conyza pyrrhopappa Sch.Bip. ex A.Rich, a medicinal plant traditionally used across tropical Africa to relieve fever. The structures of isolates have been elucidated by a combination of spectroscopic techniques. The crude extract and the isolated compounds were evaluated in the Hela-S3 cell line and in a panel of microorganisms (bacteria and fungi) at concentrations up to 50 µg/mL. The new compounds were inactive while the pentamethylated flavonoids showed low to significant activity against the cancer cell line used. However, none of the samples showed any activity against the tested microorganisms at this concentration. The present manuscript is the first investigation of the cytotoxicity of phytochemicals and extract from C. pyrrhopappa.

Cytotoxycity and antiplasmodial activity of phenolic derivatives from Albizia zygia (DC.) J.F. Macbr. (Mimosaceae).

BACKGROUND: The proliferation and resistance of microorganisms area serious threat against humankind and the search for new therapeutics is needed. The present report describes the antiplasmodial and anticancer activities of samples isolated from the methanol extract of Albizia zygia (Mimosaseae). MATERIAL: The plant extract was prepared by maceration in methanol. Standard chromatographic, HPLC and spectroscopic methods were used to isolate and identify six compounds (1-6). The acetylated derivatives (7-10) were prepared by modifying 2-O-ß-D-glucopyranosyl-4-hydroxyphenylacetic acid and quercetin 3-O-α-L-rhamnopyranoside, previously isolated from A. zygia (Mimosaceae). A two-fold serial micro-dilution method was used to determine the IC50s against five tumor cell lines and Plasmodium falciparum. RESULTS: In general, compounds showed moderate activity against the human pancreatic carcinoma cell line MiaPaca-2 (10 < IC50 < 20 µM) and weak activity against other tumor cell lines such as lung (A-549), hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7and A2058) (IC50 > 20 µM). Additionally, the two semi-synthetic derivatives of quercetin 3-O-α-L-rhamnopyranoside exhibited significant activity against P. falciparum with IC50 of 7.47 ± 0.25 µM for compound 9 and 6.77 ± 0.25 µM for compound 10, higher than that of their natural precursor (IC50 25.1 ± 0.25 µM). CONCLUSION: The results of this study clearly suggest that, the appropriate introduction of acetyl groups into some flavonoids could lead to more useful derivatives for the development of an antiplasmodial agent.

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.

In vitro antibacterial and antibiotic modifying activity of crude extract, fractions and 3',4',7-trihydroxyflavone from Myristica fragrans Houtt against MDR Gram-negative enteric bacteria.

BACKGROUND: Nutmeg is the seed kernel inside the fruit of Myristica fragrans Houtt. (Myristicaceae). It possesses various pharmacological activities but is used in Cameroon only for its flavor in making cakes. The present study thus aimed to investigate the in vitro antibacterial activity and antibiotic modifying activities of crude seed kernel methanol extract (MFS), fractions (MFSa-e) as well as 3',4',7-trihydroxyflavone from Myristica fragrans against a panel of multi-drug resistant (MDR) Gram-negative bacteria. METHODS: The modified rapid p-iodonitrotetrazolium chloride (INT) colorimetric assay was used to determine the Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) on the tested bacteria, as well as those of antibiotics in association with the extract and/or isolated compound. Column chromatography was used for the fractionation and purification of the seed kernel extract whilst the chemical structures of compounds were determined using spectroscopic techniques. RESULTS: Phytochemical investigations lead to the isolation of 3',4',7-trihydroxyflavone from the fraction MFSb. The crude extract showed antibacterial activity with MICs ranging from 32 to 1024 µg/mL on the majority of the 29 tested Gram-negative bacterial strains. Fraction MFSb inhibited the growth of 100% (29/29) of the tested bacterial strains, as well as the compound 3',4',7-trihydroxyflavone (12/12) with a MIC values ranging from 32 to 1024 µg/mL, and 4 to 128 µg/mL respectively. The lowest MIC value (4 µg/mL) was recorded with 3',4',7-trihydroxyflavone against Providencia stuartii ATCC299645 as well as the best MBC value (16 µg/mL) against the same strain. In the presence of Phenylalanine-Arginine-ß-Naphthylamide (PAßN), an efflux pumps inhibitor, the activity of the extract increased on 73.33% (11/15) meanwhile that of 3',4',7-trihydroxyflavone increased on 100% tested bacteria. The compound 3',4',7-trihydroxyflavone potentiated the activity of antibiotics in the majority of the tested bacterial strains. CONCLUSION: The results of the present work provide additional information on the use of nutmeg and it major antibacterial component, 3',4',7-trihydroxyflavone, as a potential drug in the treatment of bacterial infections including multidrug resistant phenotypes.

A new flavone from the roots of Milicia excelsa (Moraceae).

A new flavonoid identified as 2-(2,4-dihydroxyphenyl)-5-hydroxy-8,8-dimethyl-4H,8H-pyrano[2,3-f]chromen-4-one (2'-hydroxyatalantoflavone) (1) was obtained from the roots of Milicia excelsa along with five known compounds including atalantoflavone (2), neocyclomorusin (3), 6-geranylnorartocarpetin (4), cudraxanthone I (5), and betulinic acid (6). The structures of the isolates were established on the basis of their spectral data and by comparison with those reported in the literature.

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 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.