Anticholinesterase activity of ß-carboline-1, 3, 5-triazine hybrids

Abstract The ß-carboline-1,3,5-triazine hydrochlorides 8-13 were evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The analysed compounds were selective to BuChE, with IC50 values in the range from 1.0-18.8 µM being obtained. The N-{2-[(4,6-dihydrazinyl-1,3,5-triazin-2-yl)amino]ethyl}-1-phenyl-ß-carboline-3-carboxamide (12) was the most potent compound and kinetic studies indicate that it acts as a competitive inhibitor of BuChE. Molecular docking studies show that 12 strongly interacts with the residues of His438 (residue of the catalytic triad) and Trp82 (residue of catalytic anionic site), confirming that this compound competes with the same binding site of the butyrylthiocholine

Design, synthesis and biological activity of novel triazine inhibitors of Candida albicans secreted aspartic protease 2 / 药学学报

In recent years, the incidence and mortality of invasive fungal infections has increased. It is highly desirable to develop novel antifungal agents with new modes of action. Targeting virulence factors represents a new strategy for antifungal drug discovery. Secreted aspartic protease 2 (SAP2), a kind of virulence factor, is an emerging antifungal target. However, discovery of small-molecule SAP2 inhibitors remains a significant challenge. Based on the structure-activity relationship of our previously identified triazine small-molecule SAP2 inhibitor, we were able to identify two potent inhibitors, 8a and 8c, which showed excellent in vivo antifungal activity for the treatment of C. albicans infection. Moreover, compounds 8a and 8b effectively inhibited fungal biofilm. Taken together, triazine SAP2 inhibitors represent promising lead compounds for the discovery of novel antifungal agents.

Synthesis And Anticancer Screening Of Triazine Analogues

Objective: The study was aimed to investigate the cytotoxic effect of S-5H-[1,2,4]-triazino (5,6-b) indol-3-yl-3,4-phenylethane-thioate derivatives as epidermal growth factor Receptor (EGFR) inhibitors. Methods: In the present study 14 novel triazine analogues were synthesized and characterized using different spectroscopic techniques such as FT-IR, NMR and Mass Spectroscopy. The anticancer activity was performed using MCF-7 (breast cancer) and K-562 (leukaemia) cell lines. Further, molecular docking was carried out using Vlife Molecular Docking Software (MDS) on crystal structure of epidermal growth factor receptor (EGFR) to identify the binding mode of interaction with an active site. Results: Compounds MA-7, MA-8, MA-12, MA-13 and MA-14 show potent activity against cancer cell lines in the range of<10 to 84.4 µg/ml. Further molecular docking on EGFR also supports that there is a strong correlation between in silico and in vitro biological activity. The results of this study may be further useful for lead optimization process. Conclusion: The results of this study indicates that the synthesized triazine analogues can give a potential lead as an anticancer agent.

Synthesis and Anticancer Activity of Novel 2-Phenylindole Linked Imidazolothiazole, Thiazolo-s-triazine and Imidazolyl-Sugar Systems

Novel functionalized 2-phenylindole derivatives, their derived imidazolethione and 1,2,4-triazinethione weresynthesized. The bicyclic compounds thiazoloimidazole and thiazolotriazine compounds in addition to their arylidinederivatives 5-8 were synthesized. Furthermore, a thioglycoside, as well as sugar hydrazone derivatives of theimidazolylindole system, were prepared. Some of the prepared compounds were screened against four cancer celllines and compounds 2, 3a and 10 showed high cytotoxic activities. The imidazolylindol-3-one derivatives 3a showedsignificant cytotoxic effect superior to the reference drug, doxorubicin, against breast adenocarcinoma cell line.

Synthesis, Evaluation and Docking Study of 1, 3, 5-Triazine Derivatives as Cytotoxic Agents against Lung Cancer.

Knowing that dihydrofolate reductase (DHFR) is the primary target enzyme for antifolate drugs and 1,3,5-triazine derivatives containing various amino groups at position 2, 4 or 6 have been known as potent anticancer drugs, two series of tri-amino-substituted 1,3,5-triazine derivatives were designed, synthesized and evaluated as cytotoxic agents against non-small cell lung cancer (A549). The first series are N2-(4-phenylthiazol-2-yl)-1,3,5-triazine-2,4,6-triamine analogs and the second series are4-((4,6-Diamino-1,3,5-triazin-2-yl)amino)-4H-1,2,4-triazole-3-thiol analogs. Out of twenty two synthesized compounds there were thirteen compounds showed a higher cytotoxic activity against A549 cell line than methotrexate and four compounds were equipotent to methotrexate. Compounds 8e, 9a, 10e and 11e showed the highest cytotoxic activity with IC50 values of 50,42, 62 and 28 nM respectively. Molecular docking study was performed to interpret the comparative differences in the binding interactions of the synthesized novel compounds at molecular level as inhibitors of human dihydrofolate reductase (hDHFR)and to understand the structure activity relationships. The excellent anticancer activity of synthesized analogs presented in this study needs further investigation as highly promising cytotoxic lead agents against lung cancer.

Determination of 22 Triazine Herbicides Residual in Corn by Enhanced Matrix Removal QuEChERS-Ultra Flow Liquid Chromatography-Tandem Mass Spectrometry / 分析化学

An enhance matrix removal ( EMR) QuEChERS method for simultaneous determination of 22 triazine herbicide residuals such as atrazine, propazine, terbumeton, and desmetryn in corn was established and validated. The corn samples were initially extracted with acetonitrile ( MeCN ) in high-speed homogenization, and the targeted pesticides were prepared using EMR-Lipid (Enhanced matrix removal-lipid) method to clean-up and EMR-Polish to salt out, separated on a Kinetex XB-C18 with acetonitrile and 0. 1%formic acid aqueous as eluant, and then detected by UFLC-MS / MS under positive ( ESI+ ) electrospray ionization and MRM models. The average recoveries of 22 herbicides were in the range of 72% -105% at the spiked level of 5, 10 and 20 μg / kg. The relative standard deviations were less than 15% . In the method validation, correlation coefficients were higher than 0. 993 with the linear range from 1. 0 μg / L to 50 μg / L. The qualitative analysis and quantitative analysis were investigated by UFLC-MS / MS and matrix-matched calibration curves. The results showed that EMR QuEChERS combined with UFLC-MS / MS purification method was rapid, accurate and sensitive for the determination of 22 triazine herbicides residues in corn.

Anticonvulsant profile of 2-ethylthio-7-methyl-4-(4-methylphenyl)pyrazolo[1, 5-a][1, 3, 5]triazine

This work evaluates the central nervous effects in ICR strain mice of 2-ethylthio-7-methyl-4-(4-methylphenyl)pyrazolo[1,5-a][1,3,5]triazine (MH4b1), a compound obtained by an efficient one-step reaction of S,S-diethyl 4-methylbenzoylimidodithiocarbonate with 5-amino-3-methyl-1H-pyrazole, in order to assess its neuro-pharmacological profile. The tests applied were: maximal electroshock seizure (MES), pentylenetetrazole (PTZ) seizures, forced swimming, plus maze, marble burying, sleeping time, rota-rod and catalepsy. In addition, MH4b1 binding to the benzodiazepine site of the GABA-A receptor and MH4b1 inhibition of monoamine oxidase (MAO) subtypes A and B were evaluated. MH4b1 showed anticonvulsant effects in a dose dependent manner (30-300 mg/kg, p.o.) against MES and inhibition of MAO-B (IC50: 24.5 µM) without activity at the benzodiazepine site. These data suggest that MH4b1 has anticonvulsant properties related to MAO-B inhibition.

Este trabalho avalia o efeito do 2-etiltio-7-metil-4-(4-metilfenil)pirazol[1,5-a][1,3,5]triazina (MH4b1) no sistema nervoso central de camundongos ICR. O MH4b1 foi obtido por a reação de 4-metilbenzoilimidoditiocarbonato de S,S-dietil e 5-amino-3-metil-1H-pirazol em uma única etapa. O perfil neurofarmacológico foi realizado por testes de convulsão induzida por eletrochoque (MES) e pentilenotetrazol (PTZ) e por testes de nado forçado, labirinto em cruz, esconder as esferas, sono barbitúrico, rota-rod e catalepsia. Também foi avaliada a união do MH4b1 ao o local de ligação de benzodiazepínicos do receptor GABA-A e a capacidade inibitória do MH4b1 sobre a monoaminoxidase (MAO) A e B. O MH4b1 mostrou efeito anticonvulsivante dependente da dose (30-300 mg) no teste do MES e apresentou atividade inibitória da MAO-B (CI50: 24.5 µM) sem interagir com o local de ligação de benzodiazepínicos do receptor. Os resultados sugerem que o MH4b1 tem atividade anticonvulsivante relacionada com a inibição da MAO-B.

Determination of 31 Triazine Herbicides in Farmland Soils by High Performance Liquid Chromatography-Tandem Mass Spectrometry / 分析化学

A high performance liquid chromatography-tandem mass spectrometric method ( HPLC-MS/MS ) was developed for the simultaneous determination of 31 kinds of triazine herbicides in farmland soils. Samples were extracted by accelerated solvent extraction ( ASE ) and purified by Oasis MCX solid phase extraction ( SPE) cartridges, and then analyzed by HPLC-MS/MS in multiple reaction monitoring ( MRM) mode with positive electrospray ionization. The analytical column was Phenomenex Luna C18 ( 150 mm í 2. 0 mm í3 μm) and the mobile phases were acetonitrile and water containing 0. 1% (V/V) formic acid. The limits of detection (S/N≥3) were 0. 008-0. 440 μg/L. All of the triazine herbicides had good linear responses with r≥0 . 996 and the average recoveries in the spiked levels of 0 . 40-40 . 0 μg/kg ranged from 76 . 9%-102 . 0%with the RSDs of 3 . 4%-10 . 3%. The HPLC-MS/MS method had been applied for the detection of the triazine herbicide residues in farmland soils from Shenyang region and the results showed that atrazine, simazine, prometryne and atrazine-desethyl were the main triazine herbicides in the region.

Design, characterization and biological activity of a new series of s-Triazines derived with morpholine.

4,6-dimethoxypyrimidin-2-amine condensed with trichloro s-triazine. The product of the above reaction was allowed to react with Morpholine. Finally various aromatic amines derivatives were allowed to react and the product were characterized by conventional and instrumental methods. Their structures were determined and important biological properties were studied.

Non-nucleoside reverse transcriptase inhibitors(Part 18): Synthesis and anti-HIV activity of 4-allylamino or 4-azido substituted diaryltriazines / 药学学报

Eight new diaryltriazine derivatives containing 4-allylamino and 4-azido substitutes guided by molecular docking have been designed and synthesized based on our previous work.The evaluation of HIV inhibitory activity demonstrated that all compounds were potent against HIV-1 replication.The most active compound 7c exhibited activity against HIV-1 (IC50=0.034 μmol·L-1,SI=6475)and the double mutant strain (IC50=9.39 μmol·L-1)in the micromolar range, which was more potent than nevirapine.