1,3,5-Triazines: A promising scaffold for anticancer drugs development

Cascioferro, Stella; Parrino, Barbara; Spanò, Virginia; Carbone, Anna; Montalbano, Alessandra; Barraja, Paola; Diana, Patrizia; Cirrincione, Girolamo

doi:10.1016/j.ejmech.2017.09.035

Cited by 125 publications

(79 citation statements)

References 97 publications

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“…It slows down the metabolism of folic acid by competitive inhibition of enzymatic reactions involving p-aminobenzoic acid [21]. The combination of structures with biological activity (stilbenes, chalcones, piperazines, aminoalcohols/phenols, and aminobenzene sulfonamides) with a 1,3,5-triazine core (privileged structure) can lead to a significant increase in the antioxidative activity [22][23][24][25]. The molecular structure of compounds with radical scavenging activity can be very diverse.…”

Section: Introductionmentioning

confidence: 99%

Antioxidative Activity of 1,3,5-Triazine Analogues Incorporating Aminobenzene Sulfonamide, Aminoalcohol/Phenol, Piperazine, Chalcone, or Stilbene Motifs

et al. 2020

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A series of 1,3,5-triazine analogues, incorporating aminobenzene sulfonamide, aminoalcohol/phenol, piperazine, chalcone, or stilbene structural motifs, were evaluated as potential antioxidants. The compounds were prepared by using step-by-step nucleophilic substitution of chlorine atoms in starting 2,4,6-trichloro-1,3,5-triazine. Reactions were catalyzed by Cu(I)-supported on a weakly acidic resin. The radical scavenging activity was determined in terms of %inhibition activity and EC50, using the ABTS method. Trolox and ascorbic acid (ASA) were used as standards. In the lowest concentration 1 × 10−4 M, the %inhibition activity values at 0 min were comparable with both standards at least for 10 compounds. After 60 min, compounds 5, 6, 13, and 25 showed nearly twice %inhibition (73.44–87.09%) in comparison with the standards (Trolox = 41.49%; ASA = 31.07%). Values of EC50 at 60 min (17.16–27.78 μM) were 5 times lower for compounds 5, 6, 13, and 25 than EC50 of both standards (trolox = 178.33 μM; ASA = 147.47 μM). Values of EC50 correlated with %inhibition activity. Based on these results, the presented 1,3,5-triazine analogues have a high potential in the treatment of illnesses caused or related to oxidative stress.

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Section: Introductionmentioning

confidence: 99%

Antioxidative Activity of 1,3,5-Triazine Analogues Incorporating Aminobenzene Sulfonamide, Aminoalcohol/Phenol, Piperazine, Chalcone, or Stilbene Motifs

et al. 2020

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“…The 1,3,5-triazine scaffold, also known as s-triazine, and its derivatives have a wide range of applications due to broad biological activities including antiviral, antibacterial, anti-inflammatory, anti-HIV and more recently anti-cancer activity [1][2][3][4] . Specifically, sulphonamides incorporating 1,3,5-triazine moieties were extensively studied as a potent and selective carbonic anhydrase inhibitors [5][6][7][8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

Sulphonamides incorporating 1,3,5-triazine structural motifs show antioxidant, acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitory profile

Lolak

Boğa

Tuneg

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of 16 novel benzenesulfonamides incorporating 1,3,5-triazine moieties substituted with aromatic amines, dimethylamine, morpholine and piperidine were investigated. These compounds were assayed for antioxidant properties by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical decolarisation assay and metal chelating methods. They were also investigated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase, which are associated with several diseases such as Alzheimer, Parkinson and pigmentation disorders. These benzenesulfonamides showed moderate DPPH radical scavenging and metal chelating activity, and low ABTS cation radical scavenging activity. Compounds 2 b, 3d and 3 h showed inhibitory potency against AChE with % inhibition values of >90. BChE was also effectively inhibited by most of the synthesised compounds with >90% inhibition potency. Tyrosinase was less inhibited by these compounds.

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“…The 1,3,5‐triazine ( I ) (Figure ) is a simple, but privileged heterocycle, which has been incorporated as the central core ring in a number of drugs showing, to cite someone, antitumoral, antimicrobial, antiviral, or antimalarial therapeutic potential, among the diverse array of biological activities that this functional motif is able to afford to the molecules that bear it. The fusion of 1,3,5‐triazines with other rings usually results in even more versatile structures .…”

Section: Figurementioning

confidence: 99%

Synthesis, Monoamine Oxidase Inhibition and Computational Analysis of Diversely Substituted N‐Propargylated‐1,3,5‐triazines

et al. 2019

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In this work six diversely substituted N-propargylated-1,3,5triazines have been designed, synthesized, and evaluated as monoamine oxidase (MAO) inhibitors. Very surprisingly, only 4,6-dichloro-N-(prop-2-yn-1-yl)-1,3,5-triazin-2-amine (1) showed modest, but selective MAOÀ B inhibition (IC 50 = 14.2 � 0.7 μM), whose binding affinity has been investigated by computational analysis The 1,3,5-triazine (I) ( Figure 1) is a simple, but privileged heterocycle, [1a] which has been incorporated as the central core ring in a number of drugs showing, to cite someone, antitumoral, [2] antimicrobial, [3] antiviral, [4] or antimalarial [5] therapeutic potential, among the diverse array of biological activities that this functional motif is able to afford to the molecules that bear it. The fusion of 1,3,5-triazines with other rings usually results in even more versatile structures. [1b] The 1,3,5-triazine heterocyclic motif is also endowed with electronic properties that have been used with in designing new molecular structures or platforms. [6] From the synthetic point of view, the easy, and simple protocol to prepare diversely substituted 1,3,5-triazines is the key point that clearly explains the large literature available on the chemistry and reactivity of this type of compounds. The obvious starting material for the synthesis of all of them is the readily available 2,4,6-trichloro-1,3,5-triazine ("cyanuric chloride") (1) (Figure 1), bearing three chlorine atoms that can be totally or stepwise substituted by different type of O-, ad N-attacking nucleophiles leading to large and diverse families of molecules suitably functionalized at will for pharmacological analysis. [7] In particular, in the context of the therapeutic strategy based on multitarget small molecules (MTSM) [8,9] for designing novel ligands for complex diseases, such as Alzheimer's disease (AD), [10] cancer or stroke, the special features integrated in the 1,3,5-triazine (I) allow for instance the incorporation of a diverse and selected number of functional and structural motifs. In other words, the subtle and targeted incorporation of a number of pharmacophoric groups. Doing that it is expected that in only one "triazine" derivative, each pharmacophore be able to modulate its own receptor or enzymatic system, giving in all the desired combined pharmacological activity to deal with a precise pathology. The recent literature is rich and shows nice examples on how this protocol is carried out and how it works in the practice. For instance, Hoda and co-workers have reported MTSM for AD that combine the inhibition of cholinesterase (ChEs) enzymes with the inhibition of betaamyloid aggregation based on the careful selection of triazolopyrimidine-triazine scaffolds. [11] Our recent developments of novel MTSM for AD based on indolepropargylamines able to inhibit inter alia the monoamine oxidase (MAO) enzymes, and whose most advanced hitcompound is Contilisant, [12] prompted us to explore the rich [a] Dr. Figure 1. General structure of 1,3,5-triazne (I), and structur...

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1,3,5-Triazines: A promising scaffold for anticancer drugs development

Cited by 125 publications

References 97 publications

Antioxidative Activity of 1,3,5-Triazine Analogues Incorporating Aminobenzene Sulfonamide, Aminoalcohol/Phenol, Piperazine, Chalcone, or Stilbene Motifs

Antioxidative Activity of 1,3,5-Triazine Analogues Incorporating Aminobenzene Sulfonamide, Aminoalcohol/Phenol, Piperazine, Chalcone, or Stilbene Motifs

Sulphonamides incorporating 1,3,5-triazine structural motifs show antioxidant, acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitory profile

Synthesis, Monoamine Oxidase Inhibition and Computational Analysis of Diversely Substituted N‐Propargylated‐1,3,5‐triazines

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