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ChemistryOpen Jan 2023Heterocyclic systems are now considered to be an integral part of material chemistry. Thiophene, selenophene, furan, pyrrole, carbazole, triazine and others are some... (Review)
Review
Heterocyclic systems are now considered to be an integral part of material chemistry. Thiophene, selenophene, furan, pyrrole, carbazole, triazine and others are some such examples worth mentioning. 2,4,6-Tri(thiophen-2-yl)-1,3,5-triazine is a C -symmetric system with thiophene as the donor unit and s-triazine as the acceptor unit. This review gives an insight into the advances made in the thienyl-triazine chemistry over the past two to three decades. The synthetic pathways for arriving at this system and all its important derivatives are provided. The major focus is on the materials synthesized using the thienyl-triazine system, including star molecules, linear and hyperbranched polymers, porous materials and their diverse applications. This review will play a catalytic role for new dimensions to be explored in thienyl-triazine chemistry.
Topics: Thiophenes; Triazines; Polymers; Catalysis; Porosity
PubMed: 36599693
DOI: 10.1002/open.202200203 -
International Journal of Environmental... Apr 2022Wastewater treatment plants (WWTPs) represent a major point source for pesticide residue entry to aquatic environment and may threaten ecosystems and biodiversity in...
Wastewater treatment plants (WWTPs) represent a major point source for pesticide residue entry to aquatic environment and may threaten ecosystems and biodiversity in urban area. Triazine herbicides should be paid attention to for their ubiquitous occurrence in the environment and long-term residue. The present study aimed to quantify eleven compounds of triazine herbicides during wastewater treatment processes. The solid phase extraction and gas-chromatography mass spectrometry (GC-MS) determination method were developed to identify the target herbicides with approving sensitivity. The pollution levels, removal rates of eleven triazine herbicides along five different treatment stages in WWTP were investigated. The results showed that three herbicides including atrazine, simetryn and prometryn were detected. Their concentrations in influent were among 28.79 to 104.60 ng/L. Their total removal rates from influent to effluent were 14.92%, 10.79% and 4.41%, respectively indicating that they were difficult to be effectively remove during wastewater treatment. Regarding the negative impact of triazine herbicides discharged from WWTPs on downstream water quality and aquatic life, the environmental risks were assessed by calculating the Environmental Relevance of Pesticides from Wastewater Treatment Plants Index () and water cycle spreading index (). The risk assessment results denoted the possible high risks for atrazine and simetryn to alage, and simetryn concurrently posed a high risk for the daphnia, while prometryn was at medium risk to alage. Atrazine and simetryn in effluent posed high risk for algae, meanwhile, simetryn had high risk for Daphnia. These results suggested a possible threat to the aquatic environment, rendering in this way the method as a useful assessment tool. Further extensive study is needed for atrazine and simetryn in order to better understand their migration mechanism in aquatic environment.
Topics: Atrazine; Ecosystem; Environment; Environmental Monitoring; Herbicides; Prometryne; Triazines; Water Pollutants, Chemical; Water Purification
PubMed: 35457424
DOI: 10.3390/ijerph19084557 -
Molecules (Basel, Switzerland) Feb 2021This review provides an overview of the broad applicability of s-triazine. Our many years working with this intriguing moiety allow us to discuss its wide activity... (Review)
Review
This review provides an overview of the broad applicability of s-triazine. Our many years working with this intriguing moiety allow us to discuss its wide activity spectrum (inhibition against MAO-A and -B, anticancer/antiproliferative and antimicrobial activity, antibacterial activity against MDR clinical isolates, antileishmanial agent, and use as drug nano delivery system). Most of the compounds addressed in our studies and those performed by other groups contain only -substitution. Exploiting the concept of orthogonal chemoselectivity, first described by our group, we have successfully incorporated different nucleophiles in different orders into s-triazine core for application in peptides/proteins at a temperature compatible with biological systems.
Topics: Animals; Drug Discovery; Humans; Triazines
PubMed: 33562072
DOI: 10.3390/molecules26040864 -
Scientific Reports Feb 20233-Amino-4,6-dimethylpyrazolopyridine was applied as a precursor for the synthesis of some new pyridopyrazolo-triazine and pyridopyrazolo-triazole derivatives through...
3-Amino-4,6-dimethylpyrazolopyridine was applied as a precursor for the synthesis of some new pyridopyrazolo-triazine and pyridopyrazolo-triazole derivatives through diazotization, followed by coupling with many 2-cyanoacetamide compounds, ethyl 3-(phenylamino)-3-thioxopropanoate, 3-oxo-N-phenylbutanethioamide, and α-bromo-ketone reagents [namely; 2-bromo-1-(4-fluorophenyl)ethan-1-one, 5-bromo-2-(bromoacetyl)thiophene, 3-(2-bromoacetyl)-2H-chromen-2-one and/or 3-chloroacetylacetone]. The prepared compounds were identified by spectroscopic analyses as IR, H NMR, and mass data. The anticancer activity of these pyrazolopyridine analogues was investigated in colon, hepatocellular, breast, and cervix carcinoma cell lines. The pyridopyrazolo-triazine compound 5a substituted with a carboxylate group gave a distinguished value of IC = 3.89 µM against the MCF-7 cell line compared to doxorubicin as a reference drug. Also, the pyridopyrazolo-triazine compound 6a substituted with the carbothioamide function gave good activity toward HCT-116 and MCF-7 cell lines with IC values of 12.58 and 11.71 µM, respectively. The discovered pyrazolopyridine derivatives were studied theoretically by molecular docking, and this study exhibited suitable binding between the active sides of pyrazolopyridine ligands and proteins (PDB ID: 5IVE). The pyridopyrazolo-triazine compound 6a showed the highest free binding energy (- 7.8182 kcal/mol) when docked inside the active site of selected proteins.
Topics: Humans; Molecular Structure; Structure-Activity Relationship; Molecular Docking Simulation; Antineoplastic Agents; Triazines; MCF-7 Cells; Triazoles; Cell Proliferation; Drug Screening Assays, Antitumor; Cell Line, Tumor
PubMed: 36797448
DOI: 10.1038/s41598-023-29908-y -
ChemMedChem Oct 2021Efficient, environmentally and economically sustainable, and nontoxic antibacterial products are of global relevance in the fight against microorganism contamination. In...
Efficient, environmentally and economically sustainable, and nontoxic antibacterial products are of global relevance in the fight against microorganism contamination. In this work, an easy and straightforward method for the synthesis of bis-morpholino triazine quaternary ammonium salts (bis-mTQAS) is reported, starting from 2,4,6-trichloro-1,3,5-triazine or 2,4-dichloro-6-methoxy-1,3,5-triazine and various N-alkylmorpholines. Bis-mTQAS were tested as antimicrobials against Gram-negative and Gram-positive bacterial strains. The best-performing bis-mTQAS were found to achieve total disinfection against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 at 50 and 400 μg/mL, respectively. Distinctively, bis-mTQAS with the highest antimicrobial efficiency had lowest cytotoxicity.
Topics: Anti-Bacterial Agents; Dose-Response Relationship, Drug; Escherichia coli; Microbial Sensitivity Tests; Molecular Structure; Morpholines; Quaternary Ammonium Compounds; Salts; Staphylococcus aureus; Structure-Activity Relationship; Triazines
PubMed: 34288499
DOI: 10.1002/cmdc.202100409 -
Molecules (Basel, Switzerland) Jun 2022Adenosine mediates various physiological activities in the body. Adenosine receptors (ARs) are widely expressed in tumors and the tumor microenvironment (TME), and they...
Adenosine mediates various physiological activities in the body. Adenosine receptors (ARs) are widely expressed in tumors and the tumor microenvironment (TME), and they induce tumor proliferation and suppress immune cell function. There are four types of human adenosine receptor (hARs): hA, hA, hA, and hA. Both hA and hA AR play an important role in tumor proliferation. We designed and synthesized novel 1,3,5-triazine derivatives through amination and Suzuki coupling, and evaluated them for binding affinities to each hAR subtype. Compounds and showed good binding affinity to both hA and hA AR, while showed the highest binding affinity to hA AR. In this study, we discovered that inhibits cell viability, leading to cell death in lung cancer cell lines. Flow cytometry analysis revealed that caused an increase in intracellular reactive oxygen species (ROS) and a depolarization of the mitochondrial membrane potential. The binding mode of 1,3,5-triazine derivatives to hA and hA AR were predicted by a molecular docking study.
Topics: Humans; Molecular Docking Simulation; Pyrimidines; Receptor, Adenosine A2A; Receptor, Adenosine A3; Structure-Activity Relationship; Triazines
PubMed: 35807265
DOI: 10.3390/molecules27134016 -
Molecules (Basel, Switzerland) May 20231,3,5-triazine derivatives, also called s-triazines, are a series of containing-nitrogen heterocyclic compounds that play an important role in anticancer drug design and... (Review)
Review
1,3,5-triazine derivatives, also called s-triazines, are a series of containing-nitrogen heterocyclic compounds that play an important role in anticancer drug design and development. To date, three s-triazine derivatives, including altretamine, gedatolisib, and enasidenib, have already been approved for refractory ovarian cancer, metastatic breast cancer, and leukemia therapy, respectively, demonstrating that the s-triazine core is a useful scaffold for the discovery of novel anticancer drugs. In this review, we mainly focus on s-triazines targeting topoisomerases, tyrosine kinases, phosphoinositide 3-kinases, NADP+-dependent isocitrate dehydrogenases, and cyclin-dependent kinases in diverse signaling pathways, which have been extensively studied. The medicinal chemistry of s-triazine derivatives as anticancer agents was summarized, including discovery, structure optimization, and biological applications. This review will provide a reference to inspire new and original discoveries.
Topics: Humans; Female; Triazines; Antineoplastic Agents; Drug Design; Breast Neoplasms; Structure-Activity Relationship; Drug Screening Assays, Antitumor
PubMed: 37298753
DOI: 10.3390/molecules28114278 -
Cell Chemical Biology Feb 2020The triazine antitubercular JSF-2019 was of interest due to its in vitro efficacy and the nitro group shared with the clinically relevant delamanid and pretomanid....
The triazine antitubercular JSF-2019 was of interest due to its in vitro efficacy and the nitro group shared with the clinically relevant delamanid and pretomanid. JSF-2019 undergoes activation requiring FH and one or more nitroreductases in addition to Ddn. An intrabacterial drug metabolism (IBDM) platform was leveraged to demonstrate the system kinetics, evidencing formation of NO and a des-nitro metabolite. Structure-activity relationship studies focused on improving the solubility and mouse pharmacokinetic profile of JSF-2019 and culminated in JSF-2513, relying on the key introduction of a morpholine. Mechanistic studies with JSF-2019, JSF-2513, and other triazines stressed the significance of achieving potent in vitro efficacy via release of intrabacterial NO along with inhibition of InhA and, more generally, the FAS-II pathway. This study highlights the importance of probing IBDM and its potential to clarify mechanism of action, which in this case is a combination of NO release and InhA inhibition.
Topics: Animals; Antitubercular Agents; Bacterial Proteins; Drug Resistance, Bacterial; Fatty Acid Synthases; Female; Half-Life; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Nitric Oxide; Oxidoreductases; Triazines
PubMed: 31711854
DOI: 10.1016/j.chembiol.2019.10.010 -
The Journal of Organic Chemistry Oct 2021A comprehensive study of the reaction scope of methyl 1,2,3-triazine-5-carboxylate () with alkyl and aryl amidines is disclosed, reacting at room temperature at...
A comprehensive study of the reaction scope of methyl 1,2,3-triazine-5-carboxylate () with alkyl and aryl amidines is disclosed, reacting at room temperature at remarkable rates (<5 min, 0.1 M in CHCN) nearly 10000-fold faster than that of unsubstituted 1,2,3-triazine and providing the product pyrimidines in high yields. C4 Methyl substitution of the 1,2,3-triazine () had little effect on the rate of the reaction, whereas C4/C6 dimethyl substitution () slowed the room-temperature reaction (<24 h, 0.25 M) but displayed an unaltered scope, providing the product pyrimidines in similarly high yields. Measured second-order rate constants of the reaction of , the corresponding nitriles and , and 1,2,3-triazine itself () with benzamidine and substituted derivatives quantitated the remarkable reactivity of and , verified the inverse electron demand nature of the reaction (Hammett ρ = -1.50 for substituted amidines, ρ = +7.9 for 5-substituted 1,2,3-triazine), and provided a quantitative measure of the impact of 4-methyl and 4,6-dimethyl substitution on the reactivity of the methyl 1,2,3-triazine-5-carboxylate and 5-cyano-1,2,3-triazine core heterocycles.
Topics: Amidines; Carboxylic Acids; Electrons; Pyrimidines; Triazines
PubMed: 34499494
DOI: 10.1021/acs.joc.1c01553 -
Molecules (Basel, Switzerland) Sep 20222,4,6-Trichloro-1,3,5-triazine (cyanuric chloride) is an excellent coupling reagent for the preparation of highly structured multifunctional molecules. Three component...
2,4,6-Trichloro-1,3,5-triazine (cyanuric chloride) is an excellent coupling reagent for the preparation of highly structured multifunctional molecules. Three component systems based on porphyrin, cyanuric chloride and carborane clusters were prepared by a one-pot stepwise amination of cyanuric chloride with 5-(4-aminophenyl)-10,15,20-triphenylporphyrin, followed by replacement of the remaining chlorine atoms with carborane - or -nucleophiles. Some variants of 1,3,5-triazine derivatives containing porphyrin, carborane and residues of biologically active compounds such as maleimide, glycine methyl ester as well as thioglycolic acid, mercaptoethanol and hexafluoroisopropanol were also prepared. A careful control of the reaction temperature during the substitution reactions will allow the synthesis of desired compounds in a good to high yields. The structures of synthesized compounds were determined with UV-vis, IR, H NMR, B NMR, MALDI-TOF or LC-MS spectroscopic data. The dark and photocytotoxicity as well as intracellular localization and photoinduced cell death for compounds , , , and were evaluated.
Topics: Boranes; Chlorine; Magnetic Resonance Spectroscopy; Maleimides; Mercaptoethanol; Molecular Structure; Porphyrins; Triazines
PubMed: 36234729
DOI: 10.3390/molecules27196200