Crispoic acid, a new compound from Laelia marginata (Orchidaceae), and biological evaluations against parasites, human cancer cell lines and Zika virus (original) (raw)
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Antimicrobial Agents and Chemotherapy, 2006
Trypanosomiasis and leishmaniasis are important parasitic diseases affecting millions of people in Africa, Asia, and South America. In a previous study, we identified several flavonoid glycosides as antiprotozoal principles from a Turkish plant. Here we surveyed a large set of flavonoid aglycones and glycosides, as well as a panel of other related compounds of phenolic and phenylpropanoid nature, for their in vitro activities against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani. The cytotoxicities of more than 100 compounds for mammalian L6 cells were also assessed and compared to their antiparasitic activities. Several compounds were investigated in vivo for their antileishmanial and antitrypanosomal efficacies in mouse models. Overall, the best in vitro trypanocidal activity for T. brucei rhodesiense was exerted by 7,8dihydroxyflavone (50% inhibitory concentration [IC 50 ], 68 ng/ml), followed by 3-hydroxyflavone, rhamnetin, and 7,8,3,4-tetrahydroxyflavone (IC 50 s, 0.5 g/ml) and catechol (IC 50 , 0.8 g/ml). The activity against T. cruzi was moderate, and only chrysin dimethylether and 3-hydroxydaidzein had IC 50 s less than 5.0 g/ml. The majority of the metabolites tested possessed remarkable leishmanicidal potential. Fisetin, 3-hydroxyflavone, luteolin, and quercetin were the most potent, giving IC 50 s of 0.6, 0.7, 0.8, and 1.0 g/ml, respectively. 7,8-Dihydroxyflavone and quercetin appeared to ameliorate parasitic infections in mouse models. Generally, the test compounds lacked cytotoxicity in vitro and in vivo. By screening a large number of flavonoids and analogues, we were able to establish some general trends with respect to the structure-activity relationship, but it was not possible to draw clear and detailed quantitative structure-activity relationships for any of the bioactivities by two different approaches. However, our results can help in directing the rational design of 7,8-dihydroxyflavone and quercetin derivatives as potent and effective antiprotozoal agents.
Antiproliferative properties of flavone acetic acid (NSC 347512) (LM 975), a new anticancer agent
1987
The antiproliferative activiy of I&one acetic acid (LM 975) was investigated on human adenocarcinoma cell lines (HCCP2998, HCC-MI%, HCC-MI410, HT 29, LoVo), on a murine colon adenocarcinoma cell line (Colon 26), on murine pancreatic adenocarcinoma cells growing in primary culture (Pan 03) and on human normal fibroblasts (Nl). No cytotoxic effects were found against human notmaljbroblasts. LM 975 was active against murine adenocarcinoma Pan 03 and Colon 26, known to be sensitive in vivo too and, to variable extents, on human adenocarcinoma cell lines. LM 975 in vitro cytotoxic potency was relatively low. The high concentrations (1.c 1.4 mM) required to obtain a cytotoxic effect are, however, pharmacologically reasonable since they are comparable with drug plasma levels in mice or in patients treated with tolerable doses. After a relatively short LM 975 treatment (2 h) DNA, RNA and protein synthesis were inhibited in different proportions. In more sensitive cells LM 975 appeared to inhibit RNA synthesis more than DNA and protein synthesis. Inhibition of macromolecule synthesis after 2 h exposure was completely reversed in 24 h recovery. After 2 h treatment no detectable DNA breakage was found by the alkaline elution method, thus corroborating the idea that this compound does not act by causing DNA damage.
In vitro and in vivo efficacy of novel flavonoid dimers against cutaneous leishmaniasis
Antimicrobial Agents and Chemotherapy, 2014
Treatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. We previously reported that synthetic flavonoid dimers have potent antipromastigote and antiamastigote activity against Leishmania donovani, the causative agent of visceral leishmaniasis. Here, we further investigate their leishmanicidal activities against cutaneous Leishmania species. One of the flavonoid dimers (compound 39) has marked antipromastigote (50% inhibitory concentrations [IC 50 s], 0.19 to 0.69 M) and antiamastigote (IC 50 s, 0.17 to 2.2 M) activities toward different species of Leishmania that cause cutaneous leishmaniasis, including Leishmania amazonensis, Leishmania braziliensis, Leishmania tropica, and Leishmania major. Compound 39 is not toxic to peritoneal elicited macrophages, with IC 50 values higher than 88 M. In the mouse model of cutaneous leishmaniasis induced by subcutaneous inoculation of L. amazonensis in mouse footpads, intralesional administration of 2.5 mg/kg of body weight of compound 39.HCl can reduce footpad thickness by 36%, compared with that of controls values. The amastigote load in the lesions was reduced 20-fold. The present study suggests that flavonoid dimer 39 represents a new class of safe and effective leishmanicidal agent against visceral and cutaneous leishmaniasis. by guest http://aac.asm.org/
Two new flavonol glycosides, isorhamnetin 3-O-b-glucopyranoside-4 0 -O-b-xylopyranoside (1) and kaempferol 3-O-b-glucopyranoside -4 0 -O-b-xylopyranoside (2), were isolated from the defatted aqueous methanol extract of the whole plant Diplotaxis harra along with 12 known flavonols (3-14). They were characterised by chemical and spectral methods. The 70% aqueous methanol, chloroform and defatted aqueous methanol plant extracts exhibited significant antioxidant effects (nitroblue tetrazolium reduction method). Their cytotoxic activity was carried out against 11 tumour cell lines (sulphorhodamine B assay). The three extracts expressed the greatest antiproliferative activity against colon 38, P388 and MKN-28 with GI 50 (0.45, 0.4, 0.07 mg/mL) and against P388 [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay] with IC 50 (0.26, 0.24, 0.25 mg/mL), respectively. The chloroform extract showed the highest activity as eukaryotic DNA topoisomerase II inhibitors of P388 with IC 50 0.24 mg/mL. Antiviral screening of the extracts and the pure compounds against footand-mouth disease virus types A and O revealed a prominent inhibition of its cytopathic effect.
The antiprotozoan potential of flavonoids
Pharmacognosy Reviews
Flavonoids are a large group of plants secondary metabolites known for their wide range of biological and pharmacological activities including antioxidant, cytotoxic, anticancer, cardioprotective, hepatoprotective, neuroprotective, antibacterial andantimicrobial properties. However, although not always recognized, they also displayed strong antiprotozoan potentials. The purpose of this paper is to provide comprehensive review of the antiprotozoan activities of flavonoids with an emphasis on their antimalarial, antileishmanial, antitrypanosomal and antiamebial properties.
Cytotoxic Constituents of the Roots of Ekmanianthe longiflora
Journal of Natural Products, 2000
Bioactivity-directed fractionation of the CHCl 3 extract of the roots of Ekmanianthe longiflora resulted in the isolation of three new natural products, (2R,3R,4R)-3,4-dihydro-3,4-dihydroxy-2-(3-methyl-2-butenyl)-1(2H)-naphthalenone (1), (2S,3R,4R)-3,4-dihydro-3,4-dihydroxy-2-(3-methyl-2-butenyl)-1(2H)-naphthalenone (2), and (2R*,3aR*,9R*,9aR*)-9-hydroxy-2-(1-hydroxy-1-methylethyl)-2,3,3a,4,9,9a-hexahydronaphtho[2,3-b]furan-4-one (3), together with the known compounds 2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-quinone (4), 2-acetylnaphtho[2,3-b]furan-4,9-quinone (5), dehydro-iso-R-lapachone (6), R-lapachone (7), catalponol, and epi-catalponol. The structures of 1-3 were determined using a combination of NMR spectroscopic techniques, and the absolute configurations of compounds 1 and 2 were obtained using Mosher ester methodology. Compounds 4-6 showed significant cytotoxicity in a panel of human cancer cells. R-Lapachone (7) exhibited only marginal activity, and catalponol and epi-catalponol were inactive in this regard. When tested at 72 mg/kg/injection in an in vivo mouse P-388 leukemia system, compound 4 was inactive (110% T/C).
Pharmaceutical Biology, 2016
Context Chagas' disease and leishmaniasis produce significant disability and mortality with great social and economic impact. The genus Stevia (Asteraceae) is a potential source of antiprotozoal compounds. Objective Aerial parts of four Stevia species were screened on Trypanosoma cruzi. Stevia satureiifolia (Lam.) Sch. Bip. var. satureiifolia (Asteraceae) dichloromethane extract was selected for a bioassay-guided fractionation in order to isolate its active compounds. Additionally, the antileishmanial activity and the cytotoxicity of these compounds on mammalian cells were assessed. Materials and methods The dichloromethane extract was fractionated by column chromatography. The isolated compounds were evaluated using concentrations of 0-100 mg/mL on T. cruzi epimastigotes and on Leishmania braziliensis promastigotes for 72 h, on trypomastigotes and amastigotes of T. cruzi for 24 h and 120 h, respectively. The compounds' cytotoxicity (12.5-500 mg/mL) was assessed on Vero cells by the MTT assay. The structure elucidation of each compound was performed by spectroscopic methods and HPLC analysis. Results The dichloromethane extracts of Stevia species showed significant activity on T. cruzi epimastigotes. The flavonoids eupatorin (1.3%), cirsimaritin (1.9%) and 5-desmethylsinensetin (1.5%) were isolated from S. satureiifolia var. satureiifolia extract. Eupatorin and 5-desmethylsinensetin showed IC 50 values of 0.2 and 0.4 mg/mL on T. cruzi epimastigotes and 61.8 and 75.1 mg/mL on trypomastigotes, respectively. The flavonoid 5-desmethylsinensetin showed moderate activity against T. cruzi amastigotes (IC 50 value ¼ 78.7 mg/mL) and was the most active compound on L. braziliensis promastigotes (IC 50 value ¼ 37.0 mg/mL). Neither of the flavonoids showed cytotoxicity on Vero cells, up to a concentration of 500 mg/mL.
ChemMedChem, 2022
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