ABSTRACT
In this study, in vitro and in vivo methods were used to evaluate the cytotoxicity and genotoxicity properties of silver nanoparticles (Ag-NPs) made from a crude ethanolic extract of Salacia chinensis. The test Ag-NPs had no cytotoxicity on the fibroblast cell line at a concentration of 100 µg/mL, according to the MTT assay results. The Chinese hamster ovary (CHO) cell line treated with varied concentrations of test Ag-NPs, with a maximum concentration of 200 µg/mL, did not exhibit any appreciable genotoxic activity, either by comparing the results with positive controls of genotoxicity caused by Methyl methane sulfonate and Benzo (a) pyrene at the concentration of 20 µg/mL, the lack of genotoxicity was established. An in vivo study in Swiss albino mice using various concentrations (250, 500, and 1000 mg/kg) of test Ag-NPs, which were compared with positive controls, further confirmed this in vitro result pattern. Contrary to the genotoxicity caused by the positive control, mouse bone marrow micronucleus testing findings revealed the absence of genotoxicity. These findings imply that at the measured doses, the Ag-NPs produced from the crude ethanolic extract of Salacia chinensis do not exhibit any cytotoxicity or genotoxicity.
Subject(s)
Metal Nanoparticles , Salacia , Cricetinae , Animals , Mice , CHO Cells , Silver , Cricetulus , DNA Damage , EthanolABSTRACT
Pulicaria arabica has been traditionally utilized in folk medicine for various purposes such as ulcer treatments as well as antidiarrheal agent. Herein, the chemical profiles of Pulicaria arabica essential oils (PAEOs) and the in vitro antiproliferative effect of PAEOs were investigated. Hydrodistillation was employed to prepare PAEOs which were then characterized by GC/MS, while the antiproliferative effects were investigated by MTT assay as well as flow cytometric and RT-PCR analysis. Sixty-four (99.99 %) constituents were recognized from PAEOs. Carvotanacetone (36.97 %), (-)-carvomenthone (27.20 %) and benzene, 2-(1,1-dimethylethyl)-1,4-dimethoxy- (6.92 %) were the main components. PAEOs displayed IC50 values ranging from 30 to 50 µg/mL. DNA content analysis revealed that A549 cells exposed to PAEOs exhibited an increase in G1 cells population. The flow cytometry analysis results also showed that the PAEOs antiproliferative effect was mediated via apoptosis induction. Furthermore, a modulation in the pro-apoptotic markers (caspase-3 and Bax) and anti-apoptotic (Bcl-2) was also observed. In conclusion, PAEOs exhibited a moderate anti-proliferative effect on A549 cells through modulating the cell cycle progression and apoptosis initiation. These findings could offer a potential therapeutic use of PAEOs in lung cancer treatment.
ABSTRACT
Many quinazoline derivatives with pharmacological properties, such as anticancer activity, have been synthesized. Fourteen quinazoline derivatives bearing a substituted sulfonamide moiety (4a-n) were previously synthesized and fully characterized. These compounds exerted antiproliferative activity against cell lines derived from solid tumors. Herein, the antileukemic activities of these compounds (4a-n) against two different leukemia cell lines (Jurkat acute T cell and THP-1 acute monocytic) were investigated. Our investigation included examining their activity in vivo in a zebrafish embryo model. Remarkably, compounds 4a and 4d were the most potent in suppressing cell proliferation, with an IC50 value range of 4-6.5 µM. Flow cytometry analysis indicated that both compounds halted cell progression at the G2/M phase and induced apoptosis in a dose-dependent manner. RT-PCR and Western blot analyses also showed that both compounds effectively induced apoptosis by upregulating the expression of proapoptotic factors while downregulating that of antiapoptotic factors. In vivo animal toxicity assays performed in zebrafish embryos indicated that compound 4d was more toxic than compound 4a, with compound 4d inducing multiple levels of teratogenic phenotypes in zebrafish embryos at a sublethal concentration. Moreover, both compounds perturbed the hematopoiesis process in developing zebrafish embryos. Collectively, our data suggest that compounds 4a and 4d have the potential to be used as antileukemic agents.
Subject(s)
Antineoplastic Agents , Leukemia , Animals , Antineoplastic Agents/pharmacology , Cell Line , Cell Line, Tumor , Cell Proliferation , Drug Screening Assays, Antitumor , Hematopoiesis , Humans , Molecular Structure , Quinazolines/pharmacology , Structure-Activity Relationship , Sulfonamides/pharmacology , ZebrafishABSTRACT
In order to investigate for a new effective and safe anticancer drug, we synthesized a novel series of quinazoline containing biologically active substituted-sulfonamide moiety at 3- position 4a-n. The structure of the newly prepared compounds was proved by microanalysis, IR, 1H-NMR, 13C-NMR and mass spectral data. All the synthesized compounds were evaluated for their in vitro cytotoxic activity in numerous cancer cell lines including A549, HepG-2, LoVo and MCF-7 and normal HUVEC cell line. The two most active compounds 4d and 4f were then tested for their apoptosis induction using DNA content and Annexin V-FITC/PI staining. Moreover, apoptosis initiation was also confirmed using RT-PCR and Western blot. To further understand the binding preferences of quinazoline sulfonamides, docking simulations were used. Among the fourteen new synthesized compounds, we found that compounds 4d and 4f exerted the strongest cytotoxicity against MCF-7 cells with an IC50 value of 2.5 and 5 µM, respectively. Flow cytometry data revealed the ability of compounds 4d and 4f to mediate apoptosis and arrest cell cycle growth at G1 phase. Furthermore, RT-PCR and Western blot results suggested that both 4d and 4f activates apoptotic cell death pathway in MCF-7 cells. Molecular docking assessments indicated that compounds 4d and 4f fit perfectly into Bcl2's active site. Based on the biological properties, we conclude that both compounds 4d and 4f could be used as a new type of anticancer agent, which provides a scientific basis for further research into the treatment of cancer.
Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Quinazolines/pharmacology , Sulfonamides/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , HEK293 Cells , Humans , In Vitro Techniques , Molecular Docking Simulation , Quinazolines/chemistryABSTRACT
We synthesised a new series of sulphonamide-bearing quinazolinone derivatives 5-18 and evaluated their in vitro cytotoxicity in various cancer cell lines (A549, HepG-2, LoVo and MCF-7) and in normal human cells (HUVEC). Compounds 6 and 10 exhibited the higher activity against all the cancer cell lines compared with 5-flourourcil as positive control. The ability of the most promising compounds 6 and 10 to induce cell cycle arrest and apoptosis in breast cancer (MCF-7) cells was evaluated by flow cytometry. Reverse transcriptase-polymerase chain reaction and western blotting were used to evaluate the expression of apoptosis-related markers. We found that the 2-tolylthioacetamide derivative 6 and the 3-ethyl phenyl thioacetamide derivative 10 exhibited cytotoxic activity comparable to that of 5-fluorouracil as reference drug in MCF-7 and LoVo colon cancer cells. Cell cycle analysis showed a concentration-dependent accumulation of cells in the sub-G1 phase upon treatment with both compounds. The Annexin V-fluorescein isothiocyanate/propidium iodide assay showed that the compounds 6 and 10 increased the early and late apoptosis cell death modes in a dose-dependent manner. These compounds downregulated the expression of B-cell lymphoma-2 (Bcl-2), while increasing that of p53, Bcl-2-like protein 4, and caspase-7, at the mRNA and protein levels. Molecular docking of compounds 6 and 10 with Bcl-2 predicted them to show moderate - high binding affinity (6: -7.5 kcal/mol, 10: -7.9 kcal/mol) and interactions with key central substrate cavity residues. Overall, compounds 6 and 10 were found to be promising anticancer and apoptosis-inducing agents.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Molecular Docking Simulation , Quinazolinones/pharmacology , Sulfonamides/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Quinazolinones/chemical synthesis , Quinazolinones/chemistry , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/chemistryABSTRACT
Janerin is a cytotoxic sesquiterpene lactone that has been isolated and characterized from different species of the Centaurea genus. In this study, janerin was isolated form Centaurothamnus maximus, and its cytotoxic molecular mechanism was studied in THP-1 human leukemic cells. Janerin inhibited the proliferation of THP-1 cells in a dose-dependent manner. Janerin caused the cell cycle arrest at the G2/M phase by decreasing the CDK1/Cyclin-B complex. Subsequently, we found that janerin promoted THP-1 cell death through apoptosis as indicated by flow cytometry. Moreover, apoptosis induction was confirmed by the upregulation of Bax, cleaved PARP-1, and cleaved caspase 3 and the downregulation of an anti-apoptotic Bcl-2 biomarker. In addition, immunoblotting indicated a dose dependent upregulation of P38-MAPK and ERK1/2 phosphorylation during janerin treatment. In conclusion, we have demonstrated for the first time that janerin may be capable of inducing cell cycle arrest and apoptosis through the MAPK pathway, which would be one of the mechanisms underlying its anticancer activity. As a result, janerin has the potential to be used as a therapeutic agent for leukemia.
Subject(s)
Antineoplastic Agents, Phytogenic , Apoptosis/drug effects , G2 Phase Cell Cycle Checkpoints/drug effects , Leukemia , M Phase Cell Cycle Checkpoints/drug effects , MAP Kinase Signaling System/drug effects , Sesquiterpenes , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Humans , Leukemia/drug therapy , Leukemia/metabolism , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , THP-1 CellsABSTRACT
Tarchonanthus Camphoratus L. is traditionally known for its various medicinal purposes. In this study, the T. camphoratus essential oil (TCEO) was isolated via steam distillation, and its chemical constituents were determined using GC-MS. The in vitro antiproliferative effects of TCEO on A549, HepG2, MCF-7 cancer cells, and HUVEC non-tumor cells was investigated using an MTT assay. Flow cytometry analysis was conducted to evaluate cell cycle distribution using propidium iodide staining, and cell death mode using Annexin V-FITC/PI assays. The expression of some apoptosis related genes was investigated using qRT-PCR. Major constituents of TCEO included fenchol, borneol, 3-cyclohexene-1-methanol and 3-ethyl-3-methyl. Cell viability test showed that TCEO is highly effective against MCF-7 cells with IC50 12.5 µg/mL. Cell cycle arrest at the G1/S phase, and apoptosis mediation were evident in the presence of TCEO. Gene expression analysis of several pro-apoptotic and anti-apoptotic genes revealed the initiation of apoptosis in TCEO-MCF-7 cells. In conclusion, our study confirms the antiproliferative activity of the T. camphoratus essential oil.
ABSTRACT
Centaurea bruguierana, of the Asteraceae family, has a long history of use in traditional medicines for the treatment of various ailments. However, the anticancer activity and underlying mechanisms have not yet been assessed. The C. bruguierana was extracted with methanol and fractionated into four different fractions. Different cancer cells and one non-cancerous were used to examine the cytotoxic effects of these fractions using MTT assay. The most potent fraction, C. bruguierana ethyl acetate fraction (CB EtOAc), was explored for its effects on cell cycle progression and apoptosis induction by Hoechst staining and annexin V-PI double staining in MCF-7 cells. The expression of apoptosis-related genes was quantified by RT-PCR. Of all fractions, CB EtOAc was found to have the strongest antiproliferative activity (IC50 = 10 µg/mL) against MCF-7 cells. The antiproliferative activity of the CB EtOAc fraction against MCF-7 was correlated with arrested of cell cycle in the G1 phase, nuclear fragmentation, and the exposure of phosphatidylserine. The induction of apoptosis by CB EtOAc in MCF-7 cells was also associated with an increase in the Bax/Bcl-2 ratio and higher expression of caspases. Overall, our results demonstrated that CB EtOAc showed apoptosis-inducing effects, suggesting that C. bruguierana may be a promising source for a novel chemotherapeutic agents for the treatment of breast cancer.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Breast Neoplasms/pathology , Centaurea/chemistry , Plant Extracts/pharmacology , 1-Butanol , A549 Cells , Acetates , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Apoptosis Regulatory Proteins/biosynthesis , Apoptosis Regulatory Proteins/genetics , Cell Cycle Checkpoints/drug effects , Cell Division/drug effects , Cell Nucleus/drug effects , Cell Nucleus/ultrastructure , Chloroform , Drug Screening Assays, Antitumor , Female , Gene Expression Regulation, Neoplastic/drug effects , Hep G2 Cells , Human Umbilical Vein Endothelial Cells , Humans , Inhibitory Concentration 50 , MCF-7 Cells , Methanol , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Plant Components, Aerial/chemistry , SolventsABSTRACT
The present study investigates the optimization of tannase production from Aspergillus nidulans for various physicochemical parameters and harvests tannase for its chemical characterization. The maximum tannase activity was observed on the third day of incubation at 35°C and the stability was observed at pH 5.5-6.0 by holding its 100% activity. The tannase was partially purified from A. nidulans [FT10] by ammonium sulfate precipitation at different concentrations, and it was found that at 80% of ammonium sulfate concentration, the precipitate exhibited the maximum activity for tannase of 96 U/ml. LCMS showed its M/Z value as 162.3 which was reconfirmed by SDS-PAGE. The UV spectrum and FTIR confirmed the presence of two oxy- and three hydroxyl groups in the benzene ring structure. The antibacterial activity of tannase was enhanced with antibiotics such as streptomycin and ceftazidime whereas the biofilm formation was significantly inhibited by the purified tannase. The scavenging activity was greatly increased with purified component and when the concentration of the purified tannase, FT10 was increased. To the best of our knowledge, this is one of the few reports where microbial species was used as the source for producing tannase enzyme and its role in various bioactivities such as antibacterial, anti-biofilm and antioxidant activity was evaluated.
Subject(s)
Anti-Bacterial Agents/pharmacology , Aspergillus nidulans/enzymology , Carboxylic Ester Hydrolases/isolation & purification , Carboxylic Ester Hydrolases/metabolism , Anti-Bacterial Agents/isolation & purification , Bacteria/drug effects , Biofilms/drug effects , Fermentation , Fungal Proteins/metabolism , Hydrogen-Ion ConcentrationABSTRACT
Targeting EGFR has proven to be beneficial in the treatment of several types of solid tumours. So, a series of novel 2-(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g]quinazolin-2-ylthio)-N-substituted acetamide 5-19 were synthesised from the starting material 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4H)-yl) benzenesulfonamide 4, to be evaluated as dual EGFR/HER2 inhibitors. The target compounds 5-19, were screened for their cytotoxic activity against A549 lung cancer cell line. The percentage inhibition of EGFR enzyme was measured and compared with erlotinib as the reference drug. Compounds 6, 8, 10, and 16 showed excellent EGFR inhibitory activity and were further selected for screening as dual EGFR/HER2 inhibitors. The four selected compounds showed IC50 ranging from 0.009 to 0.026 µM for EGFR and 0.021 to 0.069 µM for the HER2 enzyme. Compound 8 was found to be the most potent in this study with IC50 0.009 and 0.021 µM for EGFR and HER2, respectively.
Subject(s)
Antineoplastic Agents/pharmacology , ErbB Receptors/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Quinazolines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , ErbB Receptors/metabolism , Humans , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Quinazolines/chemical synthesis , Quinazolines/chemistry , Structure-Activity RelationshipABSTRACT
An array of some new N-(substituted)-2-((4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g]quinazolin-2-yl)thio)acetamide 5-19 were synthesized from the starting compound 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4H)-yl)benzenesulfonamide 4, to be assessed for their cytotoxic activity against A549 lung cancer cell line and to determine their inhibitory effect on EGFR tyrosine kinase enzyme. Compounds 5-19 showed high activity towards A549 cell line with IC50 values of 0.12-8.70 µM. Compounds 6, 12 and 18 were the most potent in this series. These compounds were further screened as dual inhibitors for EGFR/HER2 enzymes in comparison with erlotinib and were found to possess very potent activity. Compound 12 showed the highest activity with IC50 values of 0.06 µM and 0.30 µM towards EGFR and HER2, respectively. Accordingly, the apoptotic effect of the most potent compounds 6, 12 and 18 was investigated and showed a marked increase in the level of caspases-3 by 6, 9 and 8 folds, respectively, compared to the control cells. Moreover, Molecular modeling was performed inside the active site of EGFR, keeping in mind their binding possibilities, bond lengths, angles and energy scores. It was found that the most active compounds demonstrated the best binding scores in the active site of EGFR, which may clarify their high inhibition profile.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Discovery , ErbB Receptors/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Quinazolines/pharmacology , Receptor, ErbB-2/antagonists & inhibitors , Sulfonamides/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , ErbB Receptors/metabolism , Humans , Molecular Docking Simulation , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Quinazolines/chemical synthesis , Quinazolines/chemistry , Receptor, ErbB-2/metabolism , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/chemistry , BenzenesulfonamidesABSTRACT
BACKGROUND: Several edible plants are used in Kingdom of Saudi Arabia since early time to control microbial infections. In the present study, twenty-four Saudi Arabian medicinal plants d according to traditionally used were select and investigated for the antimicrobial activities. MATERIALS AND METHODS: This study was designed at evaluating the antimicrobial activities of the methanol extracts of twenty-four species of sixteen plant families used in the traditional medicine by Saudi Arabian people for the treatment of numerous ailments of the microbial and non-microbial origin against four Gram-positive, four Gram-negative bacteria and four fungi and yeast using the agar well diffusion method. RESULTS: Of most of the plants tested were found to be active against two to eight organisms. Five plants were active against eight organisms. The data appeared that extracts of Echium arabicum (SY-176), Rhantarium epapposum (SY-Rumex vesicarus (SY-181), Ziziphus nummularia (SY-188), Caylusea hexagyna (SY-197) and Artemisia monosperma (SY-198) have anti-microbial activity against the most of tested bacteria, fungi and yeast. Whereas (SY-, the extracts of Teucrium oliverianum (SY-175), Zilla spinosa (SY-187), and Rhazya stricta (SY-195) have poor action against the tested bacteria, fungi and yeast. CONCLUSION: The antimicrobial activity of plant extracts against bacteria was more effective than against fungi.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Bacteria/drug effects , Fungi/drug effects , Magnoliopsida , Plant Extracts/pharmacology , Plants, Medicinal , Artemisia , Bacteria/growth & development , Echium , Fungi/growth & development , Microbial Sensitivity Tests , Resedaceae , Rumex , Saudi Arabia , ZiziphusABSTRACT
As a part of ongoing studies in developing new anticancer agents, novel 1,2-dihydropyridine 4, thienopyridine 5, isoquinolines 6-20, acrylamide 21, thiazolidine 22, thiazoles 23-29 and thiophenes 33-35 bearing a biologically active quinoline nucleus were synthesized. The structure of newly synthesized compounds was confirmed on the basis of elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. 2,3-Dihydrothiazole-5-carboxamides 27, 25, 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (34), 1,2-dihydroisoquinoline-7-carbonitrile (7), 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (35), 1,2-dihydroisoquinoline-7-carbonitrile (6), 2-cyano-3-(dimethylamino)-N-(quinolin-3-yl)acrylamide (21), 1,2-dihydroisoquinoline-7-carbonitriles (11) and (8) exhibited higher activity (IC50 values of 27-45 µmol L-1) compared to doxorubicin (IC50 47.9 µmol L-1). LQ quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (12), 2-thioxo-2,3-dihydrothiazole-5-carboxamide (28) and quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (15) show activity comparable to doxorubicin, while (quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (9), 2,3-dihydrothiazole-5-carboxamide (24), thieno [3,4-c] pyridine-4(5H)-one (5), cyclopenta[b]thiophene-3-carboxamide (33) and (quinolin-3-yl)-6-stryl-1,2-dihydroisoquinoline-7-carbonitrile (10) exhibited moderate activity, lower than doxorubicin.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Isoquinolines/pharmacology , Pyridines/pharmacology , Quinolines/pharmacology , Thiazoles/pharmacology , Thiazolidines/pharmacology , Thiophenes/pharmacology , Antineoplastic Agents/chemical synthesis , Breast Neoplasms/pathology , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Design , Female , Humans , Inhibitory Concentration 50 , Isoquinolines/chemical synthesis , MCF-7 Cells , Models, Molecular , Molecular Structure , Pyridines/chemical synthesis , Quinolines/chemical synthesis , Structure-Activity Relationship , Thiazoles/chemical synthesis , Thiazolidines/chemical synthesis , Thiophenes/chemical synthesisABSTRACT
BACKGROUND: Quinoline derivatives have diverse biological activities including anticancer activity. On the other hand, many sulfonamide derivatives exhibited good cytotoxic activity. Hybrids of both moieties may present novel anticancer agents. RESULTS: Chloroquinoline incorporating a biologically active benzene-sulfonamide moieties 5-21 and diarylsulfone derivatives 22 and 23 were prepared using (E)-1-(4-((E)-7-chloro-1-methylquinolin-4(1H)-ylideneamino)phenyl)-3-(dimethyl-amino)prop-2-en-1-one 4 as strategic starting material. The structure of the newly synthesized compounds were confirmed by elemental analyses and spectral data. Compound 4 was confirmed by X-ray crystallographic analysis. The prepared compounds were evaluated for their anticancer activity against Lung, HeLa, Colorectal and breast cancer cell lines. Compounds 2, 4, 7, 11, 14 and 17 showed better or comparable activity to 2', 7'-dichlorofluorescein (DCF) as reference drug. Molecular docking of the active compounds on the active site of PI3K enzyme was performed in order to explore the binding mode of the newly synthesized compounds. CONCLUSION: Compounds 2, 4, 7, 11, 14 and 17 are novel quinoline derivatives that may represent good candidates for further evaluations as anticancer agents. The mechanism of action of these compounds could be through inhibition of PI3K enzyme.Graphical abstractCompound 17 on the active site of PI3K.
ABSTRACT
In the title compound, C(16)H(12)F(3)N(3)O(2)S·0.47C(2)H(5)OH·0.53CH(3)OH, the quinoline ring system is approximately planar, with a maximum deviation of 0.035â (3)â Å, and makes a dihedral angle of 52.67â (9)° with the benzene ring. The F atoms of the -CF(3) group are disordered over two orientations, with refined site occupancies of 0.56â (2) and 0.44â (2). A single solvate site is occupied at random by ethanol or methanol, with refined site occupancies of 0.470â (6) and 0.530â (6), respectively. In the crystal, mol-ecules are linked via N-Hâ¯O, N-Hâ¯N, O-Hâ¯O and C-Hâ¯O hydrogen bonds, thereby forming sheets lying parallel to (010).