ABSTRACT
The petroleum ether extract of Baccharis darwinii showed activity against Cryptococcus neoformans and dermatophytes. Bioactivity-guided fractionation of Baccharis darwinii has resulted in the isolation of three coumarins: 5'-hydroxy aurapten (anisocoumarin H, 1), aurapten (7-geranyloxycoumarin, 2) and 5'-oxoaurapten (diversinin, 3). The structures of these compounds were characterized by spectroscopic methods. These compounds were evaluated for their antimicrobialactivity against a panel of each, bacteria and fungi. Compound 3 showed the best activities against Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes with MICs = 15.6 microg/mL, followed by compound 1 whose MICs against the same fungi were 62.5 microg/mL. In addition they showed fungicidal rather than fungistatic activity. Both compounds showed moderate activity (MICs = 125 microg/mL) against Cryptococcus neoformans. This is the first report of the presence of compound 1 in B. darwinii.
Subject(s)
Antifungal Agents/isolation & purification , Baccharis/chemistry , Coumarins/isolation & purification , Plant Extracts/pharmacology , Antifungal Agents/chemistry , Bacteria/drug effects , Coumarins/chemistry , Coumarins/pharmacology , Fungi/drug effects , Microbial Sensitivity Tests , Molecular Structure , Plant Extracts/analysis , Prenylation , Spectrum AnalysisABSTRACT
Spectral and photophysical properties of the alkaloid berberine (B) were studied in solvents with different solvent parameters, using UV/Vis absorption, emission and excitation spectroscopy. The absorption and emission maxima were found to be between 421-431 nm and 514-555 nm, respectively, leading to Stokes' shifts between 4099 and 5735 cm(-1). The fluorescence quantum yields varied between 10(-2)-10(-4), depending on the solvent. Different solvent scales have been used to study the solvatochromism of B. Linear solvation energy relationships (LSER) proposed by Kamlet-Taft suggest that B is a molecule attractive as a probe for solvent polarity and hydrogen bonding properties.
Subject(s)
Berberine/chemistry , Solvents/chemistry , Molecular Structure , Photochemistry , Spectrometry, Fluorescence , Spectrophotometry, UltravioletABSTRACT
Using a conformational systematic search combined with semiempirical and ab initio (RHF/3-21G and RHF/6-31G(d)) calculations, the conformational space of bullacin B was examined for the first time. In addition, molecular dynamics simulations were carried out to better evaluate the conformational behavior of this acetogenin. Our results indicate that bullacin B possesses a significant molecular flexibility. Although many different conformations were identified, at ab initio level, the L forms were energetically mostly preferred. Our results support the use of molecular dynamics simulations for this compound suggesting that a combined decane/water system is a good solvent system to simulate the biological environment of this molecule acting as inhibitor of complex I.
Subject(s)
Electron Transport Complex I/antagonists & inhibitors , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Furans/chemistry , Furans/pharmacology , Lactones/chemistry , Lactones/pharmacology , Models, Molecular , Molecular Conformation , Quantum Theory , Static Electricity , Surface PropertiesABSTRACT
The cytotoxic effects of four alkaloids, berberine, canadine, anonaine, and antioquine were evaluated using three different cell cultures, a primary culture (rat hepatocytes) and two cell lines (HepG2 and HeLa). Our results indicate that berberine, anonaine, and antioquine possess a significant the cytotoxic effect. In contrast, canadine does not possess cytotoxic effect at concentrations tested here. A molecular modeling study indicates that the quaternary nitrogen, the aromatic polycyclic and planar structure of berberine could be the pharmacophoric patron to produce the cytotoxic effect. In parallel our results demonstrated that canadine possess a significant antioxidant activity. Stereoelectronic aspects of this alkaloid were found to be closely related to those displayed by alpha-tocopherol and its water-soluble analogue trolox. The antioxidant activities of canadine, combined with its low-toxic effect, indicated that the potential of this alkaloid as a novel class of antioxidant agent is very interesting and deserves further research.
Subject(s)
Antioxidants/chemistry , Antioxidants/toxicity , Berberine/analogs & derivatives , Animals , Berberine/chemistry , Berberine/toxicity , Cell Survival/drug effects , Cells, Cultured , Glutathione/metabolism , Hepatocytes/drug effects , Hepatocytes/metabolism , Male , Models, Molecular , Molecular Structure , Rats , Rats, Sprague-DawleyABSTRACT
Diverse N-substituted anilines bearing hetaryl fragments were easily prepared from corresponding aldimines derived from commercially available aromatic aldehydes and anilines. 2-Furyl substituted anilines showed very good antifungal activities against dermatophytes, particularly against Trichophyton rubrum (MIC=3.12-6.25microg/mL). In addition, all active compounds, 45-47, 73, and 74, were tested for cytotoxic activities against breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines with the NCI-anticancer-drug screen. The activity of amines described in this paper, along with the low toxicity of most of them, shows promise for the future development of non-toxic new antimycotic agents.
Subject(s)
Aniline Compounds , Antifungal Agents , Antineoplastic Agents , Aniline Compounds/chemical synthesis , Aniline Compounds/chemistry , Aniline Compounds/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Screening Assays, Antitumor , Humans , Imines/chemistry , Microbial Sensitivity Tests , Molecular Structure , National Cancer Institute (U.S.) , United StatesABSTRACT
The synthesis, in vitro/in vivo antifungal evaluation and a structure-activity relationship (SAR) study of 3(2H)-pyridazinones was carried out. The results reported here may be helpful in the structural identification and understanding of the minimum structural requirements for these molecules acting as antifungal agents. In addition, the most active structure in this series was tested for its capacity of inhibiting Saccharomyces cerevisiae beta 1,3-glucan synthase and chitin synthase, enzymes that catalyze the synthesis of the major polymers of the fungal cell wall.
