ABSTRACT
The antifungal evaluation of twenty seven simple and heterocycle-fused prenyl-1,4-naphthoquinones and 1,4-anthracenediones was performed in vitro against human pathogenic yeasts (Candida spp.) and filamentous fungi (Aspergillus spp., Fusarium spp., and Trichophyton spp.). The synthetic strategy used to obtain the quinone derivatives was initially based on the Diels-Alder cycloaddition between myrcene and several p-benzoquinone derivatives, followed by cyclisation of the prenyl side chain in the case of anthracene-1,4-diones. The most promising compounds, displaying MIC values in the low µg/mL range, were those bearing one or two chlorine atoms attached to the quinone ring. Time-kill curves determined for the most potent compounds showed their fungistatic mode of action similar to that of itraconazole.
Subject(s)
Anthracenes/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Aspergillus/drug effects , Candida/drug effects , Fusarium/drug effects , Naphthoquinones/pharmacology , Trichophyton/drug effects , Animals , Anthracenes/chemical synthesis , Anthracenes/chemistry , Antifungal Agents/chemistry , Cell Survival/drug effects , Chlorocebus aethiops , Dose-Response Relationship, Drug , Microbial Sensitivity Tests , Molecular Structure , Naphthoquinones/chemical synthesis , Naphthoquinones/chemistry , Structure-Activity Relationship , Vero CellsABSTRACT
The syntheses of combretastatin A-4 from gallic acid and of three combretastatin-based hybrids are described. Starting from commercial gallic acid, the phosphonium salt (3,4,5-trimethoxybenzylphosphonium bromide) is synthesized and coupled, through a Wittig reaction, with several aldehydes, including methoxymethyl-protected isovanillin, the aldehyde y-bicyclohomofarnesal having a labdane skeleton, 3-(3-pyridyl) propanal, and furfural. The biological properties of the cis-coupled compounds as cytotoxic, antiviral and antifungal agents are also reported. In addition, pyrogallol, gallic and 3,4,5-trimethoxybenzoic acids have been studied biologically.
Subject(s)
Antifungal Agents/pharmacology , Antiviral Agents/pharmacology , Stilbenes/chemical synthesis , Stilbenes/pharmacology , Antifungal Agents/chemistry , Antiviral Agents/chemistry , Molecular BiologyABSTRACT
Introduction: Aspergillus fumigatus is most commonly associated to invasive aspergillosis. Strong antifungal activity against A. fumigatus of L. origanoides essential oil gives a new added value to this natural product from Boyacá-Colombia. Aims: The increase in fungal infections, the development of resistance and toxicity of wide-spectrum antifungals have led to a constant search for therapeutic alternatives. The chemical composition, antifungal and cytotoxic activity of nine essential oils obtained from L. origanoides were evaluated and the relationship between the antifungal activities of the oil and of its major components were explored. Methods and Results: Antifungal activity was determined following the protocols AFST-EUCAST for Candida krusei and C. parapsilosis, and CLSI-M38A for Aspergillus fumigatus and A. flavus. The GC-MS analysis identified three chemotypes: thymol, carvacrol and p-cymene/trans-beta-caryophyllene. The essential oil of the thymol chemotype was the most active in antifungal assays with MIC values of 157.5, 198.4, 125 and 31 μg ml-1 against C. parapsilosis, C. krusei, A. flavus and A. fumigatus, respectively. The major components carvacrol and thymol were not active against A. fumigatus at concentrations below 157.5 μg ml-1. In general, the oils were not cytotoxic. Conclusions: The essential oil of the thymol chemotype of L. origanoides from the region of Boyacá- Colombia showed the highest antifungal activity against A. fumigatus among all the oils and major components tested. Salud UIS 2011; 43 (2): 141-148.
Introducción: La infección por el hongo Aspergillus fumigatus está más comúnmente asociada a la aspergilosis invasiva. La fuerte actividad antimicótica del aceite esencial de L. origanoides contra A. fumigatus ha dado un nuevo valor agregado a este producto natural de Boyacá-Colombia. Objetivo: El aumento de las infecciones por hongos, el desarrollo de la resistencia y la toxicidad de los antifúngicos de amplio espectro han llevado a una constante búsqueda de alternativas terapéuticas. En este estudio fueron evaluados la composición química, la actividad antifúngica y citotóxica de nueve aceites esenciales obtenidos de L. origanoides; y la relación entre la actividad antifúngica de los aceites con respecto a la presencia de sus principales componentes. Métodos y Resultados: La actividad antifúngica se determinó siguiendo los protocolos AFST-EUCAST para Candida krusei y C. parapsilosis; y CLSI M38A para Aspergillus fumigatus y A. flavus. El análisis por GC-MS identificó tres quimiotipos: carvacrol timol y p-cymene/trans-beta-caryophyllene. El aceite esencial del quimiotipo timol fue el más activo en los ensayos antifúngicos con valores de MIC de 157,5, 198,4, 125 y 31 mg ml-1 frente a C. parapsilosis, C. krusei, A. flavus y A. fumigatus, respectivamente. El carvacrol y el timol, los principales componentes, no fueron activos frente a A. fumigatus en concentraciones inferiores a 157,5 g / ml-1. En general, los aceites no fueron citotóxicos. Conclusiones: El aceite esencial de L origanoides, quimiotipo timol, de la región de Boyacá-Colombia presentó la mayor actividad antifúngica frente a A. fumigatus entre todos los aceites evaluados; igualmente, sus principales componentes fueron los más activos en comparación a los otros quimiotipos. Salud UIS 2011; 43 (2): 141-148.
Subject(s)
Humans , Oils, Volatile , Cytotoxicity, Immunologic , Antifungal Agents , Aspergillosis , Colombia , MonoterpenesABSTRACT
Labdadienedial and a series of C15,C16-functionalized derivatives were synthesized from commercial (+)-sclareolide and evaluated for their cytotoxic, antimycotic, and antiviral activities. Their precursors were similarly evaluated.
Subject(s)
Diterpenes/chemical synthesis , Diterpenes/pharmacology , Animals , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/toxicity , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/toxicity , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/toxicity , Chlorocebus aethiops , Diterpenes/chemistry , Diterpenes/toxicity , Fungi/drug effects , HeLa Cells , Herpesvirus 1, Human/drug effects , Humans , Inhibitory Concentration 50 , Vero CellsABSTRACT
Antecedentes En la medicina tradicional de Colombia, las plantas de la familia Asteraceae se han utilizado con fines medicinales. Objetivo Evaluar la actividad antimicótica y el efecto citotóxico de 15 aceites esenciales de plantas de la familia Asteraceae. Métodos La actividad antimicótica se evaluó con las cepas Candida parapsilosis ATCC 22019, Candida krusei ATCC 6258, Aspergillus flavus ATCC 204304 y Aspergillus fumigatus ATCC 204305 de acuerdo con las técnicas EUCAST y CLSI M38-A para levaduras y hongos filamentosos, respectivamente. La actividad citotóxica se evaluó mediante la técnica del MTT en la línea celular Vero. Resultados Los aceites de las plantas Achyrocline alata y Baccharis latifolia fueron los únicos activos contra A. fumigatus (media geométrica de la concentración mínima inhibitoria=78,7 y 157,4mg/ml, respectivamente). En contraste, no se evidenció actividad de los aceites contra especies de Candida. Además, estos aceites no fueron citotóxicos en las células Vero. Conclusiones Los aceites de A. alata y B. latifolia podrían ser candidatos para la desinfección de ambientes hospitalarios y para la inhibición de formación de biopelículas por A. fumigatus(AU)
Background The plants of the Asteraceae family have been used for medicinal purposes,in traditional Colombian medicine. Aim To evaluate the antifungal activity and the cytotoxic effects of 15 essential oils from plants of the Asteraceae family. Methods Antifungal activity was evaluated against Candida parapsilosis ATCC 22019, Candida krusei ATCC 6258, Aspergillus flavus ATCC 204304 and Aspergillus fumigatus ATCC 204305 following EUCAST and CLSI M38-A standard methods, for yeast and filamentous fungi, respectively. Cytotoxic effect was evaluated on Vero cell line by MTT assay. Results The oils from the plants Achyrocline alata and Baccharis latifolia were the only ones active against A. fumigatus (GM-MIC=78.7 and 157.4mg/ml, respectively). In contrast, there was no evidence of oils active against Candida species. In addition, these oils were not cytotoxic on Vero cells. The oils of A. alata and Baccharis latifolia could be candidates for disinfecting hospital environments and for inhibiting biofilm formation by A. fumigatus Conclusions The oils of A. alata and B. latifolia could be candidates for disinfecting hospital environments and for inhibiting biofilm formation by A. fumigatus(AU)
Subject(s)
Humans , Cytotoxins/therapeutic use , Antifungal Agents/therapeutic use , Asteraceae , Oils, Volatile/therapeutic use , Aspergillus , Candida , BiofilmsABSTRACT
BACKGROUND: The plants of the Asteraceae family have been used for medicinal purposes,in traditional Colombian medicine. AIM: To evaluate the antifungal activity and the cytotoxic effects of 15 essential oils from plants of the Asteraceae family. METHODS: Antifungal activity was evaluated against Candida parapsilosis ATCC 22019, Candida krusei ATCC 6258, Aspergillus flavus ATCC 204304 and Aspergillus fumigatus ATCC 204305 following EUCAST and CLSI M38-A standard methods, for yeast and filamentous fungi, respectively. Cytotoxic effect was evaluated on Vero cell line by MTT assay. RESULTS: The oils from the plants Achyrocline alata and Baccharislatifolia were the only ones active against A. fumigatus (GM-MIC=78.7 and 157.4 microg/ml, respectively). In contrast, there was no evidence of oils active against Candida species. In addition, these oils were not cytotoxic on Vero cells. The oils of A. alata and Baccharis latifolia could be candidates for disinfecting hospital environments and for inhibiting biofilm formation by A. fumigatus CONCLUSIONS: The oils of A. alata and B. latifolia could be candidates for disinfecting hospital environments and for inhibiting biofilm formation by A. fumigatus.
Subject(s)
Achyrocline/chemistry , Antifungal Agents/isolation & purification , Aspergillus flavus/drug effects , Aspergillus fumigatus/drug effects , Baccharis/chemistry , Candida/drug effects , Oils, Volatile/pharmacology , Plant Oils/pharmacology , Animals , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/toxicity , Biofilms/drug effects , Chlorocebus aethiops , Disinfectants/isolation & purification , Disinfectants/pharmacology , Microbial Sensitivity Tests , Oils, Volatile/chemistry , Oils, Volatile/isolation & purification , Oils, Volatile/toxicity , Plant Oils/chemistry , Plant Oils/isolation & purification , Plant Oils/toxicity , Vero Cells/drug effectsABSTRACT
A series of C18-oxygenated derivatives of dehydroabietic acid were synthesized from commercial abietic acid and evaluated for their cytotoxic, antimycotic, and antiviral activities.
Subject(s)
Abietanes/chemistry , Abietanes/pharmacology , Abietanes/chemical synthesis , Animals , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Cell Line, Tumor , Fungi/drug effects , Herpesvirus 1, Human/drug effects , Humans , Hydrophobic and Hydrophilic Interactions , Inhibitory Concentration 50 , Microbial Sensitivity TestsABSTRACT
Introducción: Lippia origanoides H.B.K. (Verbenacea), es una planta aromática conocida comúnmente como orégano. Los aceites esenciales de 8 muestras de L. origanoides y algunos de sus componentes mayoritarios fueron evaluados in vitro sobre la línea tumoral HeLa y la línea no tumoral Vero para identificar su potencial citotóxico. Materiales y métodos: la concentración inhibitoria cincuenta (IC50) se determinó mediante la técnica fotocolorimétrica del MTT (3-(4,5-Dimetiltiazol-2-il)-2,5-bromuro difeniltetrazolio) y los valores de IC50 se obtuvieron por análisis estadístico mediante regresión lineal simple. El índice de selectividad (IS), definido como la IC50 en células Vero sobre IC50 en células HeLa, fue calculado con el fin de encontrar aceites o componentes con potencial citotóxico selectivo hacia líneas celulares tumorales. Resultados y conclusiones: se determinó por cromatografía de gases y espectrometría de masas GC/MS la composición química de los aceites más citotóxicos. El aceite de L. origanoides que presentó la mayor actividad citotóxica sobre células HeLa con un valor de IC50 de 9.1 ± 1 µg/mL e índice de selectividad de 7,1, fue identificado como quimiotipo trans-β-cariofileno/r-cimeno. Los componentes mayoritarios del aceite quimiotipo trans-β-cariofileno/r-cimeno fueron: trans-β-cariofileno (11.3%), r-cimeno (11,2%), α-felandreno (9,9%), limoneno (7,2%), 1,8-cineol (6,5%) y α-humuleno (6,0%). Los componentes mayoritarios evaluados no mostraron actividad citotóxica relevante sobre células HeLa, sólo el limoneno y β-mirceno presentaron valores de IS, respectivamente, de 6,97 y 3,01. Sin embargo, los valores de IC50 fueron más altos que el del aceite activo. Estos resultados sugieren que la actividad citotóxica de los aceites no se debe sólo a sus componentes mayoritarios, sino a un sinergismo entre sus componentes.
Introduction: Lippia origanoides H.B.K. (Verbenaceae) is an aromatic plant commonly called as "oregano". Eight essential oils of L. origanoides and some of their main components were evaluated in vitro on tumor cell line HeLa and non-tumor cell line Vero to identify tumoural cytotoxic potential. Materials and methods: Inhibition 50% of cell population (IC50) was determined using the photo-colorimeter technique MTT (3 - (4.5-dimethylthiazol-2-yl) -2,5-difeniltetrazolium bromide). IC50 values were obtained by linear regression analysis. The selectivity index (SI), defined as Vero IC50 on HeLa IC50, it was calculated in order to find oil or major components with selective tumor cytotoxic potential. Results and conclusions: the chemical composition of the oil most cytotoxic was determined by gas chromatography and mass spectrometry GC/MS. The L. origanoides oil identified as chemotype trans-β- caryophyllene/p-cymene showed the highest cytotoxic activity on HeLa cells with IC50 value of 9.1 ± 1 µg/mL and selectivity index of 7.1. The main components were: trans-β-caryophyllene (11.3 p-cymene (11.2%), α-phellandrene (9.9%), limonene (7.2%), 1.8-cineol (6.5%) and α-humulene (6.0%). The most of the major components did not show cytotoxic activity on HeLa cells, only limonene and β-myrcene showed IS values of 6.97 and 3.01, respectively. However, the IC50 values were higher than active oil. These results suggest that cytotoxic activities of the oils are not only due to their main components, but to a synergism among its components.
Subject(s)
Origanum , Palm Oil , ThaueraABSTRACT
Introducción: Candida spp. y Aspergillus spp. son causa importante de infecciones a nivel mundial. Considerando la resistencia de estos patógenos a algunos de los antimicóticos disponibles, es necesaria la búsqueda de nuevos agentes antimicóticos. Diferentes aceites esenciales y extractos de plantas han mostrado actividad antimicótica in vitro. El objetivo de este estudio fue evaluar la actividad antimicótica, citotóxica y la composición química de aceites esenciales de la familia Labiatae. Materiales y métodos: Se evaluó la actividad antimicótica de 22 aceites de plantas de la familia Labiatae contra C. parapsilosis ATCC 22019, C. krusei ATCC 6258, A. flavus ATCC 204304 y A. fumigatus ATCC 204305, siguiendo las técnicas estándar EUCAST y CLSI M38-A para levaduras y hongos filamentosos, respectivamente. Adicionalmente la actividad citotóxica se evaluó en la línea celular Vero mediante la técnica colorimétrica del MTT. La caracterización de los aceites esenciales se llevó a cabo por cromatografía de gases acoplada a masas. Resultados: El aceite esencial mas activo fue el de Minthostachys mollis frente a todas las cepas evaluadas con rangos concentraciones mínimas inhibitorias (CMIs) entre 250 y 375 µg/mL. El aceite de la planta Hyptis mutabilis mostró actividad frente a A. fumigatus (CMI = 396.8 µg/mL). Estos aceites esenciales no fueron citotóxicos sobre las células Vero. Los componentes principales de los aceites de las plantas M. mollis y H. mutabillis fueron epóxido de cis-piperitona y 1,8-cineol, respectivamente. Conclusiones: Los aceites esenciales de las plantas M. mollis y H. mutabillis mostraron actividad antimicótica y no fueron citotóxicos en células Vero.
Introduction: Aspergillus spp. and Candida spp. are important cause of infections worldwide. Considering the resistance of these pathogens to some antifungal agents, there is greater need to search for new antifungal agents. Many extracts and essential oils isolated from plants have shown to exert antifungal effects in vitro. The aim of this study was to evaluate the antifungal, cytotoxic effect, and chemical composition of essential oils of family Labiatae. Materials and methods: Antifungal activity of twenty two essential oils from Labiatae family was evaluated against C. parapsilosis ATCC 22019, C. krusei ATCC 6258, A. flavus ATCC 204304 y A. fumigatus ATCC 204305, following EUCAST and M38-A standard protocols for yeast and filamentous fungi, respectively. Additionally, cytotoxic activity was evaluated on Vero cell line by colorimetric assay MTT. Essential oils was characterized by gas chromatography coupled to mass spectrometry. Results: The most active oil with all strains was obtained of Minthostachys mollis (MIC range 250 - 375 µg/mL). The essential oil from Hyptis mutabillis showed activity against A. fumigatus (GM-MIC = 396.8 µg/mL). These essential oils were not cytotoxic on Vero cells. The major components of essential oils from M. mollis and H. mutabillis were cis-piperitone epoxide and 1,8-cineol, respectively. Conclusions: Essential oils of H. mutabillis and M. mollis showed antifungal activity and they were not cytotoxic on Vero cells.
Subject(s)
Fungi , OilsABSTRACT
Two essential oils of Lippia alba (Mill.) N.E. Brown (Verbenacea), the carvone and citral chemotypes and 15 of their compounds were evaluated to determine cytotoxicity and antifungal activity. Cytotoxicity assays for both the citral and carvone chemotypes were carried out with tetrazolium-dye, which showed a dose-dependent cytotoxic effect against HeLa cells. Interestingly, this effect on the evaluated cells (HeLa and the non-tumoural cell line, Vero) was lower than that of commercial citral alone. Commercial citral showed the highest cytotoxic activity on HeLa cells. The antifungal activity was evaluated against Candida parapsilosis, Candida krusei, Aspergillus flavus and Aspergillus fumigatus strains following the standard protocols, Antifungal Susceptibility Testing Subcommittee of the European Committee on Antibiotic Susceptibility Testing and CLSI M38-A. Results demonstrated that the most active essential oil was the citral chemotype, with geometric means-minimal inhibitory concentration (GM-MIC) values of 78.7 and 270.8 microg/mL for A. fumigatus and C. krusei, respectively. Commercial citral showed an antifungal activity similar to that of the citral chemotype (GM-MIC values of 62.5 microg/mL for A. fumigatus and 39.7 microg/mL for C. krusei). Although the citronellal and geraniol were found in lower concentrations in the citral chemotype, they had significant antifungal activity, with GM-MIC values of 49.6 microg/mL for C. krusei and 176.8 microg/mL for A. fumigatus.
Subject(s)
Antifungal Agents/pharmacology , Aspergillus/drug effects , Candida/drug effects , Lippia/chemistry , Monoterpenes/pharmacology , Acyclic Monoterpenes , Antifungal Agents/isolation & purification , Cyclohexane Monoterpenes , Microbial Sensitivity Tests , Monoterpenes/isolation & purification , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Plant Oils/chemistry , Plant Oils/pharmacologyABSTRACT
Two essential oils of Lippia alba (Mill.) N.E. Brown (Verbenacea), the carvone and citral chemotypes and 15 of their compounds were evaluated to determine cytotoxicity and antifungal activity. Cytotoxicity assays for both the citral and carvone chemotypes were carried out with tetrazolium-dye, which showed a dose-dependent cytotoxic effect against HeLa cells. Interestingly, this effect on the evaluated cells (HeLa and the non-tumoural cell line, Vero) was lower than that of commercial citral alone. Commercial citral showed the highest cytotoxic activity on HeLa cells. The antifungal activity was evaluated against Candida parapsilosis, Candida krusei, Aspergillus flavus and Aspergillus fumigatus strains following the standard protocols, Antifungal Susceptibility Testing Subcommittee of the European Committee on Antibiotic Susceptibility Testing and CLSI M38-A. Results demonstrated that the most active essential oil was the citral chemotype, with geometric means-minimal inhibitory concentration (GM-MIC) values of 78.7 and 270.8 μg/mL for A. fumigatus and C. krusei, respectively. Commercial citral showed an antifungal activity similar to that of the citral chemotype (GM-MIC values of 62.5 μg/mL for A. fumigatus and 39.7 μg/mL for C. krusei). Although the citronellal and geraniol were found in lower concentrations in the citral chemotype, they had significant antifungal activity, with GM-MIC values of 49.6 μg/mL for C. krusei and 176.8 μg/mL for A. fumigatus.
