Flavonoids from Boldoa purpurascens inhibit proinflammatory cytokines (TNF-α and IL-6) and the expression of COX-2.

The flavonoids comprise a large class of plant metabolites distributed in food plants. These compounds have antioxidant, antitumor, antiallergic, and anti­inflammatory effects. The molecular mechanisms of their biological activities remain to be clearly understood. We investigated the in vitro anti­inflammatory potential of a flavonoid mixture and isolated compounds from the leaves of Boldoa purpurascens. Our results provide direct evidence of the anti­inflammatory effects of the mixture, which are mediated by the inhibition of the proinflammatory cytokines tumor necrosis factor α and interleukin 6 as well as the modulation of the expression of cyclooxygenase 2.

Antiprotozoal activity of synthetic amino substituted 1-methyl-1 H-alpha-carbolines.

The antiprotozoal properties of a series of amino substituted 1-methyl-1 H-alpha-carbolines were investigated in a broad panel of parasites. Various substituents were systematically introduced at various positions on the carbocyclic ring of the parent 1-methyl-1 H-alpha-carboline. Most compounds showed a potent antiprotozoal activity, although mostly accompanied by cytotoxicity on MRC-5 cells. One compound, containing the same amino-substitution as chloroquine, showed an IC50 against Plasmodium falciparum of 2.37 microM and was reasonably selective.

Antihyperglycemic activity of extracts from Boldoa purpurascens leaves in alloxan-induced diabetic rats.

In order to investigate the potential use of Boldoa purpurascens against diabetes, the antihyperglycemic effect of an ethanol extract obtained from its leaves was evaluated at doses of 50, 100 and 200 mg/kg in rats after induction of hyperglycemia by alloxan. Insulin 5 IU/kg was used as positive control and NaCl 0.9% as negative control. A similar experiment was performed with the aqueous extract used at doses of 50 and 100 mg/kg using metformin at a dose of 50mg/kg as positive control. Statistical analysis was carried using the Kruskal-Wallis test with an interval of trust of 99%. The ethanolic and aqueous extract of B. purpurascens showed a significant decrease of blood glucose levels 72 h after administration. Phytochemical analysis of the ethanol extract showed the presence of D-pinitol, a compound known for its hypoglycemic properties. In conclusion, ethanolic as well as aqueous extracts of B. purpurascens leaves show antihyperglycemic activity, possibly due to the presence of D-pinitol and flavonoids.

Development and validation of an HPLC-DAD method for Rapid quantification of vasicine in Adhatoda vasica leaves and commercial products.

Leaves from Adhatoda vasica Nees, Acanthaceae (synonym Justicia adhatoda L.) have been widely used in traditional medicine for their beneficial effect in the treatment of respiratory diseases. Vasicine, the main quinazoline alkaloid in A. vasica, has been linked to its medicinal properties. The purpose of this work was to develop and validate a reliable analytical method for the quantification of vasicine in A. vasica leaves and commercially available products. For this purpose, a high-performance liquid chromatography method coupled to diode array detection (HPLC-DAD) was used. After optimization of the extraction process and the HPLC conditions, linearity, precision, accuracy, and specificity were checked. During the validation, six commonly available food supplements and dosage forms were tested using the validated method. The calibration model was found to be linear in the concentration range of 5.125-205 µg/mL. The average vasicine content at different concentration levels was 0.99 g/100 g with an RSD% of 0.05%. The average recovery was found to be 102.3% with an RSD of 4.3%. Additionally, it was confirmed that the validated method was still precise and accurate for quantifying vasicine in other matrices like the tested preparations. In summary, the validated method was suitable for the determination of vasicine in leaves of Adhatoda vasica, as well as for investigating the quality and the prescribed intake of several commercial products.

Prevalence, management and ethnobotanical investigation of hypertension in two Guinean urban districts.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypertension is an important public health challenge in low- and middle-income countries, and in many African countries including Guinea medicinal plants are still widely used for its treatment. MATERIALS AND METHODS: The objective of this study was to determine the prevalence of hypertension in two Guinean urban districts (Pounthioun and Dowsare), to describe its management and to collect information on traditional herbal remedies. A total of 316 participants entered the study, 28.2% (89/316) men and 71.8% (227/316) women. Of these, 181 were from Dowsare (50 men and 131 women) and 135 from Pounthioun (39 men and 96 women). The mean age of subjects was 40.8 ±â€¯14.0 years (range18 - 88years), while the majority of subjects (63.3% or 200/316) were 45-74 years old. RESULTS: The overall prevalence of hypertension was 44.9% (142/316): 46.4% (84/181) from Dowsare and 43.0% (58/135) from Pounthioun. Ethnobotanical investigations among hypertensive patients led to the collection of 15 plant species, among which Hymenocardia acida leaves and Uapaca togoensis stem bark were the most cited. Phytochemical investigation of these two plant species led to the isolation and identification of isovitexin and isoorientin from H. acida, and betulinic acid and lupeol from U. togoensis. CONCLUSION: The presence of these constituents in Hymenocardia acida leaves and Uapaca togoensis stem bark may at least in part support their traditional use against hypertension in Guinea.

Anti-inflammatory compounds from leaves and root bark of Alchornea cordifolia (Schumach. & Thonn.) Müll. Arg.

Alchornea cordifolia is one of the most widely-used plants in traditional medicine throughout Africa, principally for inflammatory, antimicrobial and parasitic diseases. In continuation of our investigations on its anti-inflammatory activity, we fractionated the leaf and root bark extracts and isolated six compounds which exhibited significant topical anti-inflammatory activity in the mouse ear oedema model using croton oil at a dose of 90 microg/cm2. Daucosterol (2), acetyl aleuritolic acid (4), N1,N2-diisopentenyl guanidine (5) and N1,N2,N3-triisopentenyl guanidine (6) were shown to be more active than indomethacin, while beta-sitosterol (1) and di(2-ethylhexyl) phthalate (3) were less effective. This is the first report on the presence of compounds 1, 2, 3 and 4 in this plant and of the anti-inflammatory activity of 3, 5 and 6. These compounds may account, at least in part, for the use of A. cordifolia in folk medicine to treat inflammation.

Antiprotozoal and cytotoxic screening of 45 plant extracts from Democratic Republic of Congo.

AIM OF THE STUDY: To evaluate in vitro the antiprotozoal and cytotoxic activities of 80% methanol extract from 45 medicinal plants collected in Sankuru (Democratic Republic of Congo) against Trypanosoma brucei brucei, Trypanosoma cruzi and the chloroquine-sensitive Ghanaian strain of Plasmodium falciparum, and MRC-5 cell lines respectively. MATERIAL AND METHODS: Different extracts were obtained by maceration of each plant part used with 80% methanol for 24h. The mixture was filtered and evaporated in vacuo to give corresponding dried extract. The activity against Trypanosoma brucei brucei and Trypanosoma cruzi were performed in 96 well tissue plates each containing 10 microl aqueous plant extract dilutions (100 to 0.01 microg/ml) with 10 microl of the parasite suspension cultured in Hirumi medium supplemented with 10% foetal calf serum, a solution of 2% penicillin/streptomycin (2% P/S) After 4 days incubation with Almar blueâ solution, fluorescence was measured at 500 nm emission and 530 nm excitation and results expressed as percentage reduction in parasite compared to control wells. The antiplasmodial activity of was assessed in vitro against the chloroquine-sensitive Ghanaian strain of Plasmodium falciparum cultured in RPMI-1640 medium by the lactate deshydrogenase assay in the presence of plant extracts (50 to 0.01 microg/ml). Cell-lines MRC-5 were cultured in MEM medium supplemented with 20mM l-glutamine, 16.5mM NaHCO(3), 5% foetal calf serum and 2% P/S solution. After 4h incubation, cell proliferation/viability was spectrophotomecally assessed at 540 nm after addition of MTT. In each assay, the IC50 value for each sample was derived by the drug concentration-response curves. RESULTS: The extracts from Alcornea cordifolia leaves, Momordica charantia whole plant, Omphalocarpum glomerata, root bark and Piptadia africanum stem bark showed good antiprotozoal activity against Trypanosoma brucei brucei with IC50 values from 0.7 to 7 microg/ml. Only Piptadenia africanum extract showed a pronounced antiprotozoal activity against Trypanosoma cruzi (IC50=4.0+/-06 microg/ml). The extracts from Alchornea cordifolia, Polyathia swaveleons stem bark, Sapium cornutum stem bark and Triclisia giletii stem bark exhibited a pronounced antiplasmodial activity against P. falciparum Ghanaian strain with IC50 values ranging from 0.5 to 3.0 microg/ml. Piptadenia africanum extract was the most cytotoxic sample (CC50=0.25 microg/ml) with poor selectivity against all selected protozoa (SI<10) while other active extracts did not show a significant cytotoxic effect against MCR-5 cell-lines with good selectivity according to the case. CONCLUSION: These active plant extracts are selected for extensive studies leading to the isolation of active constituents.

Challenges and pitfalls in antioxidant research.

Over the last decade, much research has focused on the potential health benefits of antioxidants and indeed many synthetic and natural compounds have been evaluated for their antioxidant profile. However, in several studies only a limited number of assays, often poorly validated, are used and the techniques available frequently lack specificity. These limitations may incorrectly influence the results. This review will therefore focus on several pitfalls that may emerge in vitro and in vivo antioxidant research. First, different in vitro techniques to determine antioxidant potential are discussed, including radical scavenging assays and fingerprinting methods. As a rule, a panel of different assays is indispensable to characterize and establish in vitro antioxidant activity. Furthermore, as problems of absorption, distribution, metabolism and excretion are only accounted for by in vivo studies, the need for in vivo antioxidant research is pointed out. Several methods to characterize the in vivo activity of antioxidants, including major drawbacks and pitfalls of some assays, have been discussed. The availability of both a representative "oxidative stress" animal model and a battery of well-validated assays to assess the broad diversity of oxidative damage and antioxidative defence parameters, are crucial for antioxidant research in vivo.

Ethnobotanical survey and antibacterial activity of some plants used in Guinean traditional medicine.

A total of 418 healers have been interviewed in Guinea, a coastal country of West Africa, ranging between 7 degrees 30 and 12 degrees 30 of northern latitude and 8 degrees and 15 degrees of western longitude. Plant species used by the local inhabitants to treat infectious diseases were identified using ethnobotanical, ethnographic and taxonomic methods. During these investigations, 218 plants were registered, of which the following were the most frequently used: Erythrina senegalensis, Bridelia ferruginea, Crossopteryx febrifuga, Ximenia americana, Annona senegalensis, Cochlospermum tinctorium, Cochlospermum planchonii, Lantana camara, Costus afer, Psidium guajava, Terminalia glaucescens, Uapaca somon and Swartzia madagascariensis. Most plants, and especially the leaves, were essentially used as a decoction. In order to assess antibacterial activity, 190 recipes were prepared and biologically tested, among which six showed activity (minimal inhibitory concentration<125 microg/ml) against Bacillus cereus, Mycobacterium fortuitum, Staphylococcus aureus, or Candida albicans, i.e., Entada africana, Chlorophora regia, Erythrina senegalensis, Harrisonia abyssinica, Uvaria tomentosa, and a mixture of six plants consisting of Swartzia madagascariensis, Isoberlinia doka, Annona senegalensis, Gardenia ternifolia, Terminalia glaucescens and Erythrina senegalensis.

A new decomposition product of dihydroartemisinin.

After prolonged storage, samples of dihydroartemisinin were found to contain a decomposition product with a molecular weight of 238, as evidenced by MS analysis, the formation of which was accelerated by heating at 60 degrees C for several days. This decomposition product was isolated and identified as 2-(3-oxobutyl)-3-methyl-6-(2-propanal)-cyclohexanon, known to be formed by thermolysis of dihydroartemisinin at 190 degrees C. However, during work-up of this compound a hitherto unknown decomposition product of dihydroartemisinin with a molecular weight of 210 was obtained and identified by 1H, 13C and two-dimensional NMR spectroscopy as 2-(3-oxobutyl)-3-methyl-6-ethyl-cyclohexanon. Most probably this product was formed by oxidation of the aldehyde functionality of the former decomposition product and subsequent decarboxylation.

Cytotoxicity and in vitro susceptibility of Entamoeba histolytica to Morinda morindoides leaf extracts and its isolated constituents.

An aqueous decotion (dried extract), an 80% MeOH extract from Morinda morindoides leaves, and 10 flavonoids and 4 iridoids isolated from the 80% MeOH extract were evaluated in vitro for their potential antiamoebic activity and their cytotoxic effect against MT-4 cells. Results indicated that the aqueous decoction and the 80% MeOH extract exhibited an interesting antiamoebic activity with IC(50) values of 3.1 +/- 1.7 and 1.7 +/- 0.6 microg/ml, respectively. Apigenin-7-O-glucoside and luteolin-7-O-glucoside exhibited a moderate antiamoebic activity with IC(50) values of 22.3 +/- 3.2 and 37.4 +/- 2.7 microg/ml, respectively. Kaempferol (IC(50) = 10.3 +/- 2.3 microg/ml), apigenin (IC(50) = 12.7 +/- 4.3 microg/ml), and luteolin (IC(50) = 17.8 +/- 4.3 microg/ml) showed a more pronounced activity than their corresponding glycosides. All tested iridoids displayed a very good activity with IC(50) values less than 10 microg/ml. The most active iridoids were epoxygaertneroside (IC(50) = 1.3 +/- 0.4 microg/ml) and methoxygaertneroside (IC(50) = 2.3. +/- 0.7), followed by gaertneroside and gaertneric acid with IC(50) values of 4.3 +/- 1.8 and 7.1 +/- 1.4 microg/ml, respectively. Except quercetin and quercetin-7,4'-dimethylether which have shown a cytotoxic effect with IC(50) ranging from 14 to 22 microg/ml. No correlation could be deduced between the observed antiamoebic and cytotoxic activity of these tested samples. A structure-activity relationship for isolated compounds is discussed. These findings support the medicinal report for the traditional use of Morinda morindoides leaves for the treatment of amoebiasis.

In vitro antiprotozoal activity and cytotoxicity of extracts and isolated constituents from Greenwayodendron suaveolens.

ETHNOPHARMACOLOGICAL RELEVANCE: The Nkundo people (Nkundo area of Bolongo, Mai-Ndombe district, Bandundu Province, DR Congo) use various plant parts of the tree Greenwayodendron suaveolens (Engl. & Diels) Verdc. (syn. Polyalthia suaveolens Engl. & Diels) (Annonaceae) against malaria, but its antiprotozoal constituents are not known. MATERIALS AND METHODS: The crude 80% ethanol extract from the fruits, leaves, root bark and stem bark and 16 fractions were assessed in vitro for their antiprotozoal activity against Trypanosoma brucei brucei, T. cruzi, Leishmania infantum and the chloroquine and pyrimethamine-resistant K1 strain of Plasmodium falciparum (Pf-K1). Their cytotoxic effects were evaluated against MRC-5 cells. Active constituents were isolated by chromatographic means, identified using spectroscopic methods, and evaluated in the same assays. RESULTS: The root bark extract showed the highest activity against P. falciparum K1 (IC50 0.26µg/mL) along with the stem bark alkaloid fraction (IC50 0.27µg/mL). The root bark alkaloid fraction had a pronounced activity against all selected protozoa with IC50 values <1µg/mL. The 90% methanol fractions of the different plant parts showed a pronounced activity against P. falciparum K1, with IC50 values ranging between 0.36µg/mL and 0.69µg/mL. Four constituents were isolated: the triterpenes polycarpol, and dihydropolycarpol, the latter one being reported for the first time from nature, and the alkaloids polyalthenol and N-acetyl-polyveoline. They were active to a various degree against one or more protozoa, mostly accompanied by cytotoxicity. The highest selectivity was observed for N-acetyl-polyveoline against P. falciparum K1 (IC50 2.8µM, selectivity index 10.9). CONCLUSIONS: These results may explain at least in part the traditional use of this plant species against parasitic diseases such as malaria in DR Congo.

Safety assessment of a traditionally used extract from leaves of Boldoa purpurascens.

ETHNOPHARMACOLOGICAL RELEVANCE: Boldoa purpurascens Cav. (Nyctaginaceae) is a plant species used in traditional medicine in Cuba as a diuretic. AIM OF THE STUDY: The aim of the present investigation was to evaluate the safety profile of a hydroalcoholic extract from leaves of Boldoa purpurascens. MATERIALS AND METHODS: First, an experimental study to assess the oral acute toxicity at a dose of 2000mg/kg body weight of the extract was carried out. Potential genotoxicity of the extract was evaluated using the Ames test and the micronucleus induction assay in mouse bone marrow. In the Ames test a concentration range of 50, 100, 150, 300 and 500µg/plate was tested. In the micronucleus induction assay, doses of 500, 1000 and 2000mg/kg of body weight were tested. For completeness, since the extract contains saponins, the evaluation of the hemolytic activity, ocular and skin irritation were included. RESULTS: No signs or symptoms of toxicity were observed in the oral acute toxicity test (body weight at baseline, seven days and end of the experiment of 236.41±20.07, 256.81±30.44 and 240.02±26.16 respectively for the treated group). The hydroalcoholic extract from the leaves was not mutagenic in the Ames test, and no genotoxicity was observed in the micronucleus assay. A hemolysis test at concentration of 1mg/mL confirmed hemolytic activity, which is not a safety concern since saponins are not absorbed after oral administration. In order to evaluate the percentage of protein denaturation, the ocular irritability index was calculated. The extract was found to be irritating. Finally, skin irritability was evaluated and the irritation index was equal to zero. CONCLUSIONS: Based on the toxicological evaluation of a traditionally used hydroalcoholic extract from the leaves of Boldoa purpurascens we can confirm the safety of its oral use.

Ethnomedical and ethnobotanical investigations on the response capacities of Guinean traditional health practioners in the management of outbreaks of infectious diseases: The case of the Ebola virus epidemic.

ETHNOPHARMACOLOGICAL RELEVANCE: The recent outbreak of Ebola virus infections has mostly remained confined to the West African countries Guinea-Conakry, Sierra-Leone and Liberia. Due to intense national and international mobilizations, a significant reduction in Ebola virus transmission has been recorded. While international efforts focus on new vaccines, medicines and diagnostics, no coherent national or international approach exists to integrate the potential of the traditional health practitioners (THPs) in the management of infectious diseases epidemics. Nevertheless, the first contact of most of the Ebola infected patients is with the THPs since the symptoms are similar to those of common traditionally treated diseases or symptoms such as malaria, hemorrhagic syndrome, typhoid or other gastrointestinal diseases, fever and vomiting. MATERIALS AND METHODS: In an ethnomedical survey conducted in the 4 main Guinean regions contacts were established with a total of 113 THPs. The socio-demographic characteristics, the professional status and the traditional perception of Ebola Virus Disease (EVD) were recorded. RESULTS: The traditional treatment of the main symptoms was based on 47 vegetal recipes which were focused on the treatment of diarrhea (22 recipes), fever (22 recipes), vomiting (2 recipes), external antiseptic (2 recipes), hemorrhagic syndrome (2 recipes), convulsion and dysentery (one recipe each). An ethnobotanical survey led to the collection of 54 plant species from which 44 identified belonging to 26 families. The most represented families were Euphorbiaceae, Caesalpiniaceae and Rubiaceae. Literature data on the twelve most cited plant species tends to corroborate their traditional use and to highlight their pharmacological potential. CONCLUSIONS: It is worth to document all available knowledge on the traditional management of EVD-like symptoms in order to evaluate systematically the anti-Ebola potential of Guinean plant species.

Biologically active bisbenzylisoquinoline alkaloids from the root bark of Epinetrum villosum.

Methanol and water extracts of the root of Epinetrum villosum (Exell) Troupin (Menispermaceae) were found to exhibit antimicrobial and antiplasmodial activities. Investigation of the active methanol fraction led to the isolation of four bisbenzylisoquinoline alkaloids, i.e., cycleanine, cycleanine N-oxide, isochondodendrine and cocsoline. Structures were established by spectroscopic methods. Cocsoline displayed antibacterial and antifungal activities (MIC values of 1000-15.62 and 31.25 microg/ml, respectively). Isochondodendrine was found to have the most potent antiplasmodial activity (IC50 = 0.10 microg/ml), whereas the IC50 on HCT-116 human colon carcinoma cells was 17.5 microg/ml (selectivity index 175). Cycleanine acted against HIV-2 (EC50=1.83 microg/ml) but was at least 10-fold less active against HIV-1. Cycleanine N-oxide showed no activity towards all tested microorganisms.

In vitro antiprotozoal activity and cytotoxicity of extracts and fractions from the leaves, root bark and stem bark of Isolona hexaloba.

ETHNOPHARMACOLOGICAL RELEVANCE: Isolona hexaloba (Pierre) Engl. and Diels (Annonaceae) is traditionally used in D.R. Congo against parasitic diseases including malaria. MATERIALS AND METHODS: Two crude aqueous extracts, 3 crude methanol extracts and 3 crude 80% ethanol extracts from the leaves, root bark and stem bark together with 12 subfractions from the crude 80% ethanol extracts were evaluated in vitro for their antiprotozoal activity against Trypanosoma brucei brucei, T. cruzi, Leishmania infantum and the chloroquine and pyrimethamine resistant K1 strain of Plasmodium falciparum. Their cytotoxic effects against MRC-5 cell lines were also assessed. RESULTS: Results indicated that the most pronounced activities against T. b. brucei were recorded for the crude methanol extracts of root bark (IC50=1.97 µg/ml; SI>32.49) and leaves (IC50=2.65 µg/ml; SI>24.15). Three samples displayed good activity against T. cruzi: the 80% methanol extract of leaves (IC50=8.33 µg/ml; SI>3.92), its petroleum ether fraction (IC50=8.50 µg/ml; SI=2.52) and the crude aqueous extract of the stem bark (IC50=9.31 µg/ml; SI=3.46). The crude aqueous extract of the leaves exhibited a pronounced and selective activity against L. infantum (IC50=2.00 µg/ml; SI>32). The crude methanol extract of leaves (IC50=6.35 µg/ml; SI>10.10) and the 2 dichloromethane soluble fractions of the 80% ethanol extracts from root bark (IC50=6.96 µg/ml; SI=6.1) and stem bark (IC50=8 µg/ml; SI>8.00) showed good activity and selectivity against L. infantum. The most active samples against Plasmodium falciparum K1 were the leaves crude 80% ethanol extract (0.92 µg/ml) and its fractions: alkaline aqueous (IC50=0.27 µg/ml), 90% methanol (0.90 µg/ml) and dichloromethane (1.04 µg/ml), respectively, with promising selectivity indexes of 35

Synthesis and biological evaluation of dihydrobenzofuran lignans and related compounds as potential antitumor agents that inhibit tubulin polymerization.

A series of 19 related dihydrobenzofuran lignans and benzofurans was obtained by a biomimetic reaction sequence involving oxidative dimerization of p-coumaric, caffeic, or ferulic acid methyl esters, followed by derivatization reactions. All compounds were evaluated for potential anticancer activity in an in vitro human disease-oriented tumor cell line screening panel that consisted of 60 human tumor cell lines arranged in nine subpanels, representing diverse histologies. Leukemia and breast cancer cell lines were relatively more sensitive to these agents than were the other cell lines. Compounds 2c and 2d, but especially 2b (methyl (E)-3-¿2-(3, 4-dihydroxyphenyl)-7-hydroxy-3-methoxycarbonyl-2, 3-dihydro-1-benzofuran-5-ylprop-2-enoate), the dimerization product of caffeic acid methyl ester, containing a 3',4'-dihydroxyphenyl moiety and a hydroxyl group in position 7 of the dihydrobenzofuran ring, showed promising activity. The average GI(50) value (the molar drug concentration required for 50% growth inhibition) of 2b was 0.3 microM. Against three breast cancer cell lines, 2b had a GI(50) value of <10 nM. Methylation, reduction of the double bond of the C(3)-side chain, reduction of the methoxycarbonyl functionalities to primary alcohols, or oxidation of the dihydrobenzofuran ring to a benzofuran system resulted in a decrease or loss of cytotoxic activity. Compound 2b inhibited mitosis at micromolar concentrations in cell culture through a relatively weak interaction at the colchicine binding site of tubulin. In vitro it inhibited tubulin polymerization by 50% at a concentration of 13 +/- 1 microM. The 2R, 3R-enantiomer of 2b was twice as active as the racemic mixture, while the 2S,3S-enantiomer had minimal activity as an inhibitor of tubulin polymerization. These dihydrobenzofuran lignans (2-phenyl-dihydrobenzofuran derivatives) constitute a new group of antimitotic and potential antitumor agents that inhibit tubulin polymerization.

4'-Hydroxy-3-methoxyflavones with potent antipicornavirus activity.

4'-Hydroxy-3-methoxyflavones are natural compounds with known antiviral activities against picornaviruses such as poliomyelitis and rhinoviruses. In order to establish a structure-activity relationship a series of analogues were synthesized, and their antiviral activities and cytotoxicities were compared with those of flavones from natural origin. The 4'-hydroxyl and 3-methoxyl groups, a substitution in the 5 position and a polysubstituted A ring appeared to be essential requirements for a high activity. The most interesting compound was 4',7-dihydroxy-3-methoxy-5,6-dimethylflavone possessing in vitro TI99 values of greater than 1000 and greater than 200 against poliovirus type 1 and rhinovirus type 15, respectively. This compound was also active against other rhinovirus serotypes (2, 9, 14, 29, 39, 41, 59, 63, 70, 85, and 89) tested, having MIC50 values ranging from 0.016 to 0.5 micrograms/mL. Finally in contrast to quercetin it showed to be not mutagenic in concentrations up to 2.5 mg in the Ames test.