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Current Topics in Medicinal Chemistry 20201,3,5-Triazine and azole can interact with various therapeutic targets, and their derivatives possess promising in vitro and in vivo anticancer activity. Hybrid... (Review)
Review
1,3,5-Triazine and azole can interact with various therapeutic targets, and their derivatives possess promising in vitro and in vivo anticancer activity. Hybrid molecules have the potential to enhance efficiency, overcome drug resistance and reduce side effects, and many hybrid molecules are under different phases of clinical trials, so hybridization of 1,3,5-triazine with azole may provide valuable therapeutic intervention for the treatment of cancer. Substantial efforts have been made to develop azole-containing 1,3,5-triazine hybrids as novel anticancer agents, and some of them exhibited excellent activity. This review emphasizes azole-containing 1,3,5-triazine hybrids with potential anticancer activity, and the structure-activity relationships as well as the mechanisms of action are also discussed to provide comprehensive and target-oriented information for the development of this kind of anticancer drugs.
Topics: Antineoplastic Agents; Azoles; Cell Proliferation; Cell Survival; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Structure-Activity Relationship; Triazines
PubMed: 32156236
DOI: 10.2174/1568026620666200310122741 -
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 -
Mini Reviews in Medicinal Chemistry 2020Triazine is the six-membered heterocyclic ring containing three nitrogens, which replace the carbon-hydrogen unit in the benzene ring. Based on nitrogen position present... (Review)
Review
Triazine is the six-membered heterocyclic ring containing three nitrogens, which replace the carbon-hydrogen unit in the benzene ring. Based on nitrogen position present in the ring system, it is categorized in three isomeric forms, i.e., 1, 2, 3-triazine (vicinal triazine), 1, 2, 4-triazine (asymmetrical triazine or isotriazine) and 1, 3, 5-triazine (symmetrical or s-triazine or cyanidine). Triazines have a weakly basic property. Their isomers have much weaker resonance energy than benzene structure, so nucleophilic substitution reactions are more preferred than electrophilic substitution reactions. Triazine isomers and their derivatives are known to play important roles possessing various activities in medicinal and agricultural fields such as anti-cancer, antiviral, fungicidal, insecticidal, bactericidal, herbicidal, antimalarial and antimicrobial agents.
Topics: Anti-Infective Agents; Antineoplastic Agents; Bacteria; Fungi; Humans; Insecticides; Neoplasms; Triazines
PubMed: 32727324
DOI: 10.2174/1389557520666200729160720 -
Archiv Der Pharmazie Jun 20211,3,5-Triazine and its derivatives have been the epicenter of chemotherapeutic molecules due to their effective biological activities, such as antibacterial,... (Review)
Review
1,3,5-Triazine and its derivatives have been the epicenter of chemotherapeutic molecules due to their effective biological activities, such as antibacterial, fungicidal, antimalarial, anticancer, antiviral, antimicrobial, anti-inflammatory, antiamoebic, and antitubercular activities. The present review represents a summarized report of the crucial biological activities possessed by substituted 1,3,5-triazine derivatives, with special attention to the most potent compounds.
Topics: Anti-Infective Agents; Antineoplastic Agents; Antioxidants; Chemistry, Pharmaceutical; Humans; Models, Molecular; Structure-Activity Relationship; Triazines
PubMed: 33760298
DOI: 10.1002/ardp.202000363 -
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 -
European Journal of Medicinal Chemistry Dec 2017The synthesis, the antitumor activity, the SAR and, whenever described, the possible mode of action of 1,2,4-triazine derivatives, their N-oxides, N,N'-dioxides as well... (Review)
Review
The synthesis, the antitumor activity, the SAR and, whenever described, the possible mode of action of 1,2,4-triazine derivatives, their N-oxides, N,N'-dioxides as well as the benzo- and hetero-fused systems are reported. Herein are treated derivatives disclosed to literature from the beginning of this century up to 2016. Among the three possible triazine isomers, 1,2,4-triazines are the most studied ones and many derivatives having remarkable antitumor activity have been reported in the literature and also patented reaching advanced phases of clinical trials.
Topics: Animals; Antineoplastic Agents; Chemistry Techniques, Synthetic; Drug Discovery; Drug Screening Assays, Antitumor; Humans; Neoplasms; Triazines
PubMed: 28851503
DOI: 10.1016/j.ejmech.2017.08.009 -
Advanced Drug Delivery Reviews Jun 2012The use of triazine dendrimers as drug delivery systems benefits from their synthetic versatility and well-defined structure. Triazine dendrimers can be designed and... (Review)
Review
The use of triazine dendrimers as drug delivery systems benefits from their synthetic versatility and well-defined structure. Triazine dendrimers can be designed and readily synthesized to display orthogonally functional surfaces that facilitate post-synthetic manipulation such as attachment of drug, PEGylation, and/or the installation of ligands or reporting groups. The synthesis is scalable, and large generations can be accessed. To date, triazine dendrimers have been probed for a variety of medicinal applications including drug delivery with an emphasis on cancer, nonviral DNA and RNA delivery systems, in sensing applications, and as bioactive materials. Specifically, triazine adducts with paclitaxel, camptothecin, brefeldin A, and desferrioxamine have been prepared and assessed. Paclitaxel constructs show promising activity in vivo. The use of these materials in fluorescence-based glucose sensors is being pursued. Glycosylated triazine dendrimers interfere with signal transduction in the Toll-4 receptor pathway.
Topics: Animals; Dendrimers; Drug Delivery Systems; Gene Transfer Techniques; Humans; Toll-Like Receptor 4; Triazines
PubMed: 22465784
DOI: 10.1016/j.addr.2012.03.008 -
Critical Reviews in Analytical Chemistry 2015Gas chromatography (GC) and high-performance liquid chromatography (HPLC) coupled to different detectors, and in combination with different sample extraction methods,... (Review)
Review
Gas chromatography (GC) and high-performance liquid chromatography (HPLC) coupled to different detectors, and in combination with different sample extraction methods, are most widely used for analysis of triazine herbicides in different environmental samples. Nowadays, many variations and modifications of extraction and sample preparation methods such as solid-phase microextraction (SPME), hollow fiber-liquid phase microextraction (HF-LPME), stir bar sportive extraction (SBSE), headspace-solid phase microextraction (HS-SPME), dispersive liquid-liquid microextraction (DLLME), dispersive liquid-liquid microextraction based on solidification of floating organic droplet (DLLME-SFO), ultrasound-assisted emulsification microextraction (USAEME), and others have been introduced and developed to obtain sensitive and accurate methods for the analysis of these hazardous compounds. In this review, several analytical properties such as linearity, sensitivity, repeatability, and accuracy for each developed method are discussed, and excellent results were obtained for the most of developed methods combined with GC and HPLC techniques for the analysis of triazine herbicides. This review gives an overview of recent publications of the application of GC and HPLC for analysis of triazine herbicides residues in various samples.
Topics: Chromatography; Herbicides; Triazines
PubMed: 25849823
DOI: 10.1080/10408347.2014.927731 -
Molecules (Basel, Switzerland) Jan 2023Since the number of people with Alzheimer's disease (AD) continues to rise, new and effective drugs are urgently needed to not only slow down the progression of the...
Since the number of people with Alzheimer's disease (AD) continues to rise, new and effective drugs are urgently needed to not only slow down the progression of the disease, but to stop or even prevent its development. Serotonin 5-HT receptor (5-HTR) ligands are still a promising therapeutic target for the treatment of AD. 1,3,5-Triazine derivatives, as novel structures lacking an indole or a sulfone moiety, have proven to be potent ligands for this receptor. In present work, new derivatives of the compound MST4 (4-((2-isopropyl-5-methylphenoxy)methyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine), the potent 5-HTR antagonist (K = 11 nM) with promising ADMET and in vivo properties, were designed. The synthesized compounds were tested for their affinity towards 5-HTR and other receptor (off)targets (serotonin 5-HT, 5-HT and dopamine D). Based on the new results, 4-(2-tert-butylphenoxy)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine () was selected for extended in vitro studies as a potent and selective 5-HTR ligand (K = 13 nM). Its ability to permeate the blood-brain barrier (BBB) and its hepatotoxicity were evaluated. In addition, X-ray crystallography and solubility studies were also performed. The results obtained confirm that 6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine derivatives, especially compound , are promising structures for further pharmacological studies as 5-HTR ligands.
Topics: Humans; Serotonin; Structure-Activity Relationship; Receptors, Serotonin; Alzheimer Disease; Ligands; Triazines
PubMed: 36770774
DOI: 10.3390/molecules28031108 -
Acta Crystallographica. Section C,... Sep 2022Two new 1,2,4-triazine-containing sulfonamide derivatives, namely, 4-bromo-N-(5,6-diphenyl-2H-1,2,4-triazin-3-ylidene)benzenesulfonamide, CHBrNOS, 3a, and methyl...
Two new 1,2,4-triazine-containing sulfonamide derivatives, namely, 4-bromo-N-(5,6-diphenyl-2H-1,2,4-triazin-3-ylidene)benzenesulfonamide, CHBrNOS, 3a, and methyl 2-{[(5,6-diphenyl-1,2,4-triazin-3-yl)sulfamoyl]methyl}benzoate, CHNOS, 3b, which crystallize in the different sulfonimide and sulfonamide tautomeric forms, respectively, were synthesized and characterized by spectroscopic, X-ray diffraction and theoretical calculation methods. Both molecules adopt a very similar conformation of the common part of the structure and the differences occur within the substituents on the sulfonamide group. The amino groups characteristic for the existing tautomeric forms are involved in strong intermolecular N-H...N and N-H...O hydrogen bonds in 3a and 3b, respectively. The Hirshfeld surface analysis showed that H...H contacts constitute a high percentage of the intermolecular interactions. Theoretical calculations at the ab initio DFT/B3LYP/6-311++G(d,p) level showed that the two tautomeric forms observed for 3a and 3b can co-exist in chloroform, ethanol and water solutions, with a distinct predominance of the sulfonamide form; the participation of the sulfonimide form increases with increasing solvent polarity.
Topics: Crystallography, X-Ray; Hydrogen Bonding; Models, Molecular; Sulfonamides; Triazines
PubMed: 36063373
DOI: 10.1107/S2053229622007781