Triazine as a promising scaffold for its versatile biological behavior

Singla, Prinka; Luxami, Vijay; Paul, Kamaldeep

doi:10.1016/j.ejmech.2015.07.037

Cited by 121 publications

(59 citation statements)

References 134 publications

(130 reference statements)

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“…The s-triazine ring provides convenient fundament for the development of biologically active compounds with lower toxicity and higher efficiency than other non-triazine heterocyclic compounds. 21 Although to date, few compounds have reached the level of clinical trials, the perspective to find harmless agents with therapeutic potential, especially in cancer treatment, stimulates scientists' efforts to search an appropriate compound in the s-triazine derivatives group. So far, research in this field has been focused on molecules with high molecular weight and complex structure.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Cytotoxicity of Cyanuric Acid and Selected Derivatives

Batsalova¹,

Kolchakova²,

Dzhambazov³

2018

Toxicol Forensic Med Open J

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Background Cyanuric acid and its derivatives belong to the group of s-triazines. They have wide industrial application, generally in the production of pesticides, bleaching agents and disinfectants. Recent reports showed significant negative effect of cyanuric acid in combination with melamine but low general cytotoxicity of cyanuric acid alone. However, evaluations of cyanuric acid toxicity against different human cell types using a panel of in vitro assays have not been performed. In addition, little is known about the cytotoxicity and potential antitumor effects of certain cyanuric acid derivatives, for example trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate. Aim To investigate the toxicity of cyanuric acid, trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate using different cancer cell lines and normal fibroblasts. Materials and Methods MTT, Neutral red and clonogenic assays were used to characterize the in vitro cytotoxicity of cyanuric acid, trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate. Different concentrations of the compounds were tested on three cancer cell lines (HeLa, A549, CaOV) and normal human fibroblasts. IC 50 values were calculated and compared. Intracellular ATP measurements and microscopic evaluations of cellular morphology after exposure to cyanuric acid, trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate were performed. Results Among the three test-agents trichloroisocyanuric acid (TCIC) demonstrated the highest cytotoxicity in vitro. Interestingly, MTT assays indicated that the toxic effects of TCIC were mainly directed towards cancer cells affecting mitochondrial functionality. Clonogenicity of cancer cell lines was completely inhibited in the presence of low concentrations of the triazine. Exposition to TCIC influenced the morphology and intracellular ATP concentration in both cancer cells and normal fibroblasts but the observed effects were stronger in cancer cells. Conclusion The order of cytotoxicity of the tested compounds is as follows: trichloroisocyanuric acid>cyanuric acid>1,3,5-tris(2-hydroxyethyl) isocyanurate. Trichloroisocyanuric acid demonstrates selective antitumor effect.

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Section: Discussionmentioning

confidence: 99%

In Vitro Cytotoxicity of Cyanuric Acid and Selected Derivatives

Batsalova¹,

Kolchakova²,

Dzhambazov³

2018

Toxicol Forensic Med Open J

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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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“…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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Triazine as a promising scaffold for its versatile biological behavior

Cited by 121 publications

References 134 publications

In Vitro Cytotoxicity of Cyanuric Acid and Selected Derivatives

In Vitro Cytotoxicity of Cyanuric Acid and Selected Derivatives

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

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

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