Synthesis and in vitro antiprotozoal activity of some 2- amino-4-phenyloxazole derivatives

Purpose: To prepare some 2-amino-4-(p-substituted phenyl)-oxazole derivatives and to evaluate their in vitro antiprotozoal activity against Giardia lamblia and Trichomonas vaginalis.Methods: The 2-amino-4-(p-substituted phenyl)-oxazoles (a-g) were synthesized by microwave (MW) irradiation of mixtures of p-substituted 2-bromoacetophenones and urea in dimethylformamide (DMF). All compounds were identified by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy and lowand high-resolution mass spectrometry (HRMS). NMR assignments were made based on heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond correlation (HMBC) experiments. Each synthesized compound’s melting point was determined. Antiprotozoal activity against Giardia intestinalis and Trichomonas vaginalis was quantified using a rigorous and sensitive subculture method. The commercial drug, metronidazole, was used as positive control. The 50 % inhibitory concentration (IC50) of the antiprotozoal agents for each protozoa was determined.Results: Seven 2-amino-4-(p-substituted phenyl)-oxazoles (a-g) were synthesized. The most active compounds against G. lamblia was 2-amino-4-(p-benzoyloxyphenyl)-oxazole (3d) with an IC50 of 1.17 μM, while compound 3e (2-amino-4-(p-bromophenyl)-oxazole) showed the highest anti-trichomonal activity (IC50, 1.89 μM).Conclusion: The in vitro antigiardial activity of 2-amino-4-(p-benzoyloxyphenyl) oxazole was higher than that exhibited by metronidazole; however, it is necessary increase the number of synthetic derivatives in order to be able to determine their structure-activity relationship.Keywords: Antiprotozoal, 2-Amino-4-phenyl-oxazoles, Giardia lamblia, Trichomonas vaginali

ANTIPROTOZOAL ACTIVITY OF EXTRACTS OF ELAEODENDRON TRICHOTOMUM (CELASTRACEAE)

Background: Chagas disease, amebiasis, giardiasis and trichomoniasis represent a serious health problem in Latin America. The drugs employed to treat these illnesses produce important side effects and resistant strains have appeared. The present study was aimed to evaluate the antiprotozoal activity of leaves, stem bark and root bark of Elaeodendron trichotomum, a celastraceus, that is used in Mexico as an anti-infective in febrile-type diseases. Materials and methods: Dichloromethane and methanol extracts of leaves, bark and roots of Elaeodendron trichotomum were tested against Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, and Trypanosoma cruzi. A quantitative HPLC analysis of pristimerin and tingenone was performed. Results: The dichloromethane extract of roots was active against E. histolytica, G. lamblia, T. vaginalis, and T. cruzi, at IC50’s of 0.80, 0.44, 0.46, and 2.68 μg/mL, respectively. The HPLC analysis revealed the presence of tingenone (3.84%) and pristimerin (0.14%). Conclusions: The dichloromethane extract of the roots bark showed significant activity against all screened protozoa

Isolation and Identification of Cytotoxic Compounds from Aeschynomene fascicularis, a Mayan Medicinal Plant

The plant Aeschynomene fascicularis (Fabaceae) has been used in Mayan traditional medicine in the Yucatan peninsula. However, the compounds present in the plant responsible for its curative properties have not yet been investigated. Aeschynomene fascicularis root bark was extracted with 100% methanol to obtain a crude extract. The methanol extract was partitioned successively with solvents with increasing polarity to obtain the corresponding hexane (Hx), dichloromethane (DCM) and ethyl acetate fractions (EtOAc), as well as a residual water-alcoholic fraction. These fractions were tested for their cytotoxic activities using an MTT assay against Hep-2 cancer cell lines. The Hx fraction led to the isolation of spinochalcone C (1), spinochalcone A (2), isocordoin (3) and secundiflorol G (4). Their structures were identified based on spectroscopic evidence and chemical properties. All compounds were subjected to cytotoxicity and antiproliferative assays against a panel of seven cell lines, including one normal-type cell line. Spinochalcone A (2) exhibited cytotoxic activity against DU-145 cell line and antiproliferative activity against the KB cell line. Secundiflorol G (4) showed strong cytotoxic activity towards KB and Hep-2 cell lines. In addition, isocordoin (3) showed moderate activity on KB, Hep-2 and DU-145 cell lines. The active Compounds 2, 3 and 4 are potential therapeutic entities against cancer

Apoptotic and Cell Cycle Effects of Triterpenes Isolated from Phoradendron wattii on Leukemia Cell Lines

Current antineoplastic agents present multiple disadvantages, driving an ongoing search for new and better compounds. Four lupane-type triterpenes, 3α,24-dihydroxylup-20(29)-en-28-oic acid (1), 3α,23-dihydroxy-30-oxo-lup-20(29)-en-28-oic acid (2), 3α,23-O-isopropylidenyl-3α,23-dihydroxylup-20(29)-en-28-oic acid (3), and 3α,23-dihydroxylup-20(29)-en-28-oic acid (4), previously isolated from Phoradendron wattii, were evaluated on two cell lines of chronic (K562) and acute (HL60) myeloid leukemia. Compounds 1, 2, and 4 decreased cell viability and inhibit proliferation, mainly in K562, and exhibited an apoptotic effect from 24 h of treatment. Of particular interest is compound 2, which caused arrest in active phases (G2/M) of the cell cycle, as shown by in silico study of the CDK1/Cyclin B/Csk2 complex by molecular docking. This compound [3α,23-dihydroxy-30-oxo-lup-20(29)-en-28-oic acid] s a promising candidate for incorporation into cancer treatments and deserves further study

Lupane Triterpene Derivatives Improve Antiproliferative Effect on Leukemia Cells through Apoptosis Induction

Leukemia is one of the most frequent types of cancer. No effective treatment currently exists, driving a search for new compounds. Simple structural modifications were made to novel triterpenes isolated from Phoradendron wattii. Of the three resulting derivatives, 3α-methoxy-24-hydroxylup-20(29)-en-28-oic acid (T1m) caused a decrease in the median inhibitory concentration (IC50) on the K562 cell line. Its mode of action was apparently apoptosis, ROS generation, and loss of mitochondrial membrane potential (MMP). Molecular docking analysis showed T1m to produce lower binding energies than its precursor for the Bcl-2 and EGFR proteins. Small, simple, and viable modifications to triterpenes can improve their activity against leukemia cell lines. T1m is a potentially promising element for future research. Clarifying the targets in its mode of action will improve its applicability

Lupane-Type Triterpenes of <i>Phoradendron vernicosum</i>

Three new lupane-type triterpenes, 3α,24-dihydroxylup-20(29)-en-28-oic acid (<b>1</b>), 3α,23-dihydroxy-30-oxolup-20(29)-en-28-oic acid (<b>2</b>), and 3α,23-<i>O</i>-isopropylidenyl-3α,23-dihydroxylup-20­(29)-en-28-oic acid (<b>3</b>), together with eight known compounds (<b>4</b>–<b>11</b>) were isolated from a methanol extract of <i>Phoradendron vernicosum</i> aerial parts. The chemical structures of <b>1</b>–<b>3</b> were determined on the basis of spectroscopic data interpretation. The isolated compounds were tested against seven human cancer cell lines and two normal cell lines

ANTIPROTOZOAL ACTIVITY OF EXTRACTS OF ELAEODENDRON TRICHOTOMUM (CELASTRACEAE)

Background: Chagas disease, amebiasis, giardiasis and trichomoniasis represent a serious health problem in Latin America. The drugs employed to treat these illnesses produce important side effects and resistant strains have appeared. The present study was aimed to evaluate the antiprotozoal activity of leaves, stem bark and root bark of Elaeodendron trichotomum, a celastraceus, that is used in Mexico as an anti-infective in febrile-type diseases. Materials and methods: Dichloromethane and methanol extracts of leaves, bark and roots of Elaeodendron trichotomum were tested against Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, and Trypanosoma cruzi. A quantitative HPLC analysis of pristimerin and tingenone was performed. Results: The dichloromethane extract of roots was active against E. histolytica, G. lamblia, T. vaginalis, and T. cruzi, at IC50’s of 0.80, 0.44, 0.46, and 2.68 μg/mL, respectively. The HPLC analysis revealed the presence of tingenone (3.84%) and pristimerin (0.14%). Conclusions: The dichloromethane extract of the roots bark showed significant activity against all screened protozoa