Synergistic mutual potentiation of antifungal activity of Zuccagnia punctata Cav. and Larrea nitida Cav. extracts in clinical isolates of Candida albicans and Candida glabrata

Background: Zuccagnia punctata Cav. (Fabaceae) and Larrea nitida Cav. (Zygophyllaceae) are indistinctly or jointly used in traditional medicine for the treatment of fungal-related infections. Although their dichloromethane (DCM) extract have demonstrated moderate antifungal activities when tested on their own, antifungal properties of combinations of both plants have not been assessed previously. Purpose: The aim of this study was to establish with statistical rigor whether Z. punctata (ZpE) and L. nitida DCM extract (LnE) interact synergistically against the clinically important fungi Candida albicans and Candida glabrata and to characterize the most synergistic combinations. Study design: For synergism assessment, the statistical-based Boik's design was applied. Eight ZpE–LnE fixed-ratio mixtures were prepared from four different months of 1 year and tested against Candida strains. Lϕ (Loewe index) of each mixture at different fractions affected (ϕ) allowed for the finding of the most synergistic combinations, which were characterized by HPLC fingerprint and by the quantitation of the selected marker compounds. Methods: Lϕ and confidence intervals were determined in vitro with the MixLow method, once the estimated parameters from the dose–response curves of independent extracts and mixtures, were obtained. Markers (four flavonoids for ZpE and three lignans for LnE) were quantified in each extract and their combinations, with a valid HPLC–UV method. The 3D-HPLC profiles of the most synergistic mixtures were obtained by HPLC–DAD. Results: Three over four IC50ZpE/IC50LnE fixed-ratio mixtures displayed synergistic interactions at effect levels ϕ > 0.5 against C. albicans. The dosis of the most synergistic (Lϕ = 0.62) mixture was 65.96 µg/ml (ZpE = 28%; LnE = 72%) containing 8 and 36% of flavonoids and lignans respectively. On the other hand, one over four IC50ZpE/IC50LnE mixtures displays synergistic interactions at ϕ > 0.5 against C. glabrata. The dosis of the most synergistic (Lϕ = 0.67) mixture was 168.23 µg/ml (ZpE = 27%; LnE = 73%) with 9.7 and 31.6% of flavonoids and lignans respectively. Conclusions: Studies with the statistical-based MixLow method, allowed for the finding of the most ZpE–LnE synergistic mixtures, giving support to a proper joint use of both antifungal herbs in traditional medicine.Fil: Butassi, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Svetaz, Laura Andrea. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ivancovich, Juan J.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Feresin, Gabriela Egly. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tapia, Alejandro A.. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Synthesis and in vitro Evaluation of Antifungal Properties of Some 4-Aryl-3-Methyl-1,2,3,4-Tetrahydroquinolines Derivatives

Two series of 4-aryl-3-methyl-1,2,3,4-tetrahydroquinoline derivatives were efficiently synthesized according to a two-step synthesis and evaluated as potential antifungal agents. The key step was the formation of the corresponding N-benzyltetrahydroquinolines 5 via a three-component cationic imino Diels-Alder cycloaddition. The second step was a catalytic debenzylation to obtain the N-unprotected tetrahydroquinolines 6. The products were isolated and purified by column chromatography. Substances were characterized using nuclear magnetic resonance (NMR) mass spectrometry (MS) and infrared spectroscopy (IR). All compounds were tested in vitro against standardized, clinically important fungi, including yeasts, hialohyphomycetes, and dermatophytes. These studies showed that between the tetrahydroquinoline series tested, compounds 6f and 6g showed antifungal activity, specifically against dermatophytes. The compound 6-methoxy-4-(4-hydroxi-3-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline 6g exhibited the best in vitro activity (MIC 32-65 μg/mL). The results indicated that the elimination of benzyl group from the N-benzyltetrahydroquinolines derivatives, as well as the introduction of a hydroxyl group in the 4-aryl substituent caused a significant improvement in the antifungal activity. These results were supplemented by the in silico prediction; most of the tetrahydroquinolines evaluated showed high bioavailability, high drugs score and low potential risk

Synthesis and in vitro Evaluation of Antifungal Properties of Some 4-Aryl-3-Methyl-1,2,3,4-Tetrahydroquinolines Derivatives

Two series of 4-aryl-3-methyl-1,2,3,4-tetrahydroquinoline derivatives were efficiently synthesized according to a two-step synthesis and evaluated as potential antifungal agents. The key step was the formation of the corresponding N-benzyltetrahydroquinolines 5 via a three-component cationic imino Diels-Alder cycloaddition. The second step was a catalytic debenzylation to obtain the N-unprotected tetrahydroquinolines 6. The products were isolated and purified by column chromatography. Substances were characterized using nuclear magnetic resonance (NMR) mass spectrometry (MS) and infrared spectroscopy (IR). All compounds were tested in vitro against standardized, clinically important fungi, including yeasts, hialohyphomycetes, and dermatophytes. These studies showed that between the tetrahydroquinoline series tested, compounds 6f and 6g showed antifungal activity, specifically against dermatophytes. The compound 6-methoxy-4-(4-hydroxi-3-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline 6g exhibited the best in vitro activity (MIC 32-65 μg/mL). The results indicated that the elimination of benzyl group from the N-benzyltetrahydroquinolines derivatives, as well as the introduction of a hydroxyl group in the 4-aryl substituent caused a significant improvement in the antifungal activity. These results were supplemented by the in silico prediction; most of the tetrahydroquinolines evaluated showed high bioavailability, high drugs score and low potential risk

Artigo Comparative pharmacobotanic study and ethnopharmacological uses of the "Botones de oro" from Argentinean folk medicine

RESUMO: "Estudos farmacobotânicos comparativos e utilizações ethnopharmacológicas do "botões d'ouro" da medicina popular Argentina". As partes aéreas de seis plantas argentinas -conhecidas geralmente como "botões d'ouro" -são usadas indistintamente na medicina popular ou para obter remédios ervais e fitoterápicos. No entanto, estas entidades pertencem a três gêneros da tribo Helenieae (Asteraceae): Gaillardia, Helenium e Hymenoxys, sendo as espécies mais utilizadas Gaillardia megapotamica var. megapotamica (Spreng.) Bak.; G. megapotamica var. scabiosoides (Arn.) Bak.; G. megapotamica var. radiata (Griseb.) Bak.; Helenium donianum (Hook. & Arn.) Seckt; H. argentinum Ariza e Hymenoxys anthemoides (Juss.) Cass. Neste trabalho, foram estudadas as relações entre os táxons mencionados a partir do ponto de vista morfológico, a sua coexistência em populações naturais e suas ações farmacológicas reputadas. As suas características histológicas são descritas e ilustradas, a fim de obter uma exata identificação botânica dos produtos encontrados no mercado, de forma a garantir a sua qualidade, especialmente porque as amostras são freqüentemente já pulverizadas ou em pó. Unitermos: Medicina popular, Asteraceae, Helenieae, botões d'ouro, estudos farmacobotânicos, utilizações etnofarmacológicas. ABSTRACT: The aerial parts of six Argentinean plants -commonly known as "botones de oro"-are indistinctly used either in folk medicine or to obtain herbal remedies and phytotherapics. However, these entities belong to three different genera of the Tribe Helenieae (Asteraceae): Gaillardia, Helenium and Hymenoxys, being the most used species Gaillardia megapotamica var. megapotamica (Spreng.) Bak.; G. megapotamica var. scabiosoides (Arn.) Bak.; G. megapotamica var. radiata (Griseb.) Bak.; Helenium donianum (Hook. & Arn.) Seckt; H. argentinum Ariza and Hymenoxys anthemoides (Juss.) Cass. In this work, we studied the relationships between the mentioned taxa from the morphological point of view, their coexistence in natural populations and their reputed pharmacological actions. Their histological features are described and illustrated, in order to obtain an accurate botanical identification of the products found in the market so as to guarantee their quality, especially because the samples are often already powdered or grounded

Inter­molecular inter­action energies and molecular conformations in N -substituted 4-aryl-2-methyl­imidazoles with promising in vitro anti­fungal activity

A convenient one-pot synthesis of 4-aryl-2-methyl-N-phenacylimidazoles (4) through a microwave-assisted pseudo-tricomponent reaction of -bromoacetophenones (1) with acetamidine hydrochloride (2) is reported. Ketones (4) were successfully used as substrates for the preparation of the respective N-(2- hydroxyethyl)imidazoles (5) with yields up to 87%. The synthesized compounds were characterized by NMR and high-resolution mass spectrometry analyses, and several structures were confirmed and studied by single-crystal X-ray diffraction. The analysis of the whole-of-molecule interactions shows that, despite the difference in the atom–atom contacts forming the crystals, dispersion energies make the largest contribution to the formation of the solids, giving an isotropic tendency in the topology of the energy framework diagrams for pairs of molecules. In addition, the in vitro antifungal activity of both families of compounds [ketones (4) and alcohols (5)] against Candida albicans and Cryptococcus neoformans was evaluated, where the 2,4-dichlorophenylsubstituted alcohol (5f), an isomer of the drug miconazole, showed the highest activity (IC50 = 7.8 mg ml1 against C. neoformans).Fil: Elejalde Cadena, Nerith Rocio. Universidad de los Andes; ColombiaFil: Butassi, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zacchino, Susana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Macías, Mario A.. Universidad de los Andes; ColombiaFil: Portilla, Jaime. Universidad de los Andes; Colombi