Potential Triazole-based Molecules for the Treatment of Neglected Diseases

Mantoani, Susimaire P.; Andrade, Peterson de; Chierrito, Talita Perez Cantuaria; Figueredo, Andreza S.; Carvalho, Ivone

doi:10.2174/0929867324666170727103901

Cited by 13 publications

(6 citation statements)

References 112 publications

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“…Briefly, from a set of in-house and commercially available azides and alkynes, a small series of 25 compounds was synthesized via Copper-catalyzed Azide-Alkyne Cycloaddition reaction (CuAAC) in good yields and complete regioselectivity control since only 1,4-disubstituted 1,2,3-triazoles were obtained. 26 Compounds bearing either aminoethyl-quinoline (compounds 01-08), benzyl-piperazine (compounds 09-16) or benzyl-piperidine (compounds 17-25) scaffolds were linked through the triazole ring to generate a diverse range of aryl and heteroaryl compounds (indanone, phthalimide, indole, naphthyl, quinazoline, benznidazole and coumarine) (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

Santos

Pilger

Vandermeulen

et al. 2020

Bioorganic & Medicinal Chemistry

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Human T cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that infects approximately 10-20 million people worldwide and causes an aggressive neoplasia (adult T-cell leukemia/lymphoma -ATL). Therapeutic approaches for the treatment of ATL have variable effectiveness and poor prognosis, thus requiring strategies to identify novel compounds with activity on infected cells. In this sense, we initially screened a small series of 25 1,2,3-triazole derivatives to discover cell proliferation inhibitors and apoptosis inducers in HTLV-1-infected T-cell line (MT-2) for further assessment of their effect on viral tax activity through inducible-tax reporter cell line (Jurkat LTR-GFP).Eight promising compounds (02, 05, 06, 13, 15, 21, 22 and 25) with activity ≥ 70% were initially selected, based on a suitable cell-based assay using resazurin reduction method, and evaluated towards cell cycle, apoptosis and Tax/GFP expression analyses through flow cytometry. Compound 02 induced S phase cell cycle arrest and compounds 05, 06, 22 and 25 promoted apoptosis. Remarkably, compounds 22 and 25 were also able to reduce GFP expression in an inducible-tax reporter cell, which suggests an effect on Tax viral protein. More importantly, compounds 02, 22 and 25 were not cytotoxic in human hepatoma cell line (Huh-7). Therefore, the discovery of 3 active and non-cytotoxic compounds against HTLV-1-infected cells can potentially contribute, as an initial promising strategy, to the development process of new drugs against ATL.

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Section: Resultsmentioning

confidence: 99%

Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

Santos

Pilger

Vandermeulen

et al. 2020

Bioorganic & Medicinal Chemistry

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“…The click approach using thermodynamically tested CuAAC exhibits exclusive characteristics (e.g., better tolerance for many functional entities and pH fluctuations, facile and milder reaction settings, and compatibility with diverse solvents along with water). These preferred traits make CuAAC a powerful tool for designing, developing, and reshaping complex organic entities of biological relevance. − …”

Section: Introductionmentioning

confidence: 99%

“…A number of seminal reviews and two important reference books dealing with click chemistry have appeared in the literature, − ...…”

Section: Introductionmentioning

confidence: 99%

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications

et al. 2021

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Copper(I)-catalyzed 1,3-dipolar cycloaddition between organic azides and terminal alkynes, commonly known as CuAAC or click chemistry, has been identified as one of the most successful, versatile, reliable, and modular strategies for the rapid and regioselective construction of 1,4-disubstituted 1,2,3-triazoles as diversely functionalized molecules. Carbohydrates, an integral part of living cells, have several fascinating features, including their structural diversity, biocompatibility, bioavailability, hydrophilicity, and superior ADME properties with minimal toxicity, which support increased demand to explore them as versatile scaffolds for easy access to diverse glycohybrids and well-defined glycoconjugates for complete chemical, biochemical, and pharmacological investigations. This review highlights the successful development of CuAAC or click chemistry in emerging areas of glycoscience, including the synthesis of triazole appended carbohydrate-containing molecular architectures (mainly glycohybrids, glycoconjugates, glycopolymers, glycopeptides, glycoproteins, glycolipids, glycoclusters, and glycodendrimers through regioselective triazole forming modular and bio-orthogonal coupling protocols). It discusses the widespread applications of these glycoproducts as enzyme inhibitors in drug discovery and development, sensing, gelation, chelation, glycosylation, and catalysis. This review also covers the impact of click chemistry and provides future perspectives on its role in various emerging disciplines of science and technology.

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“…There remains, however, a need for in-depth research on the synthesis of highly functionalized quinazolinones from various substrate combinations. In this sense, substituted 1,2,3-triazoles are an important and useful class of heterocycles and have received considerable attention because of their application in organic synthesis, medicinal chemistry, and materials science [19][20][21][22][23][24]. For instance, the hybrid molecule containing quinoline and 1,2,3-triazole nucleus, 1-(7-chloroquinolin-4-yl)-N-(4-methoxybenzyl)-5-methyl-1H-1,2,3-triazole-4 carboxamide (QTC-4-MeOBnE A), exerts therapeutic effect through multiple pathways involved in AD (Figure 1) [25,26].…”

Section: Introductionmentioning

confidence: 99%

Selective Synthesis of 2-(1,2,3-Triazoyl) Quinazolinones through Copper-Catalyzed Multicomponent Reaction

et al. 2021

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We describe here our results from the copper-catalyzed three component reaction of 2-azidobenzaldehyde, anthranilamide and terminal alkynes, using Et3N as base, and DMSO as solvent. Depending on the temperature and amount of Et3N used in the reactions, 1,2,3-triazolyl-quinazolinones or 1,2,3-triazolyl-dihydroquinazolinone could be obtained. When the reactions were performed at 100 °C using 2 equiv. of Et3N, 1,2,3-triazolyl-dihydroquinazolinone was formed in 82% yield, whereas reactions carried out at 120 °C using 1 equiv. of Et3N provided 1,2,3-triazolyl-quinazolinones in moderate-to-good yields.

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Potential Triazole-based Molecules for the Treatment of Neglected Diseases

Cited by 13 publications

References 112 publications

Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications

Selective Synthesis of 2-(1,2,3-Triazoyl) Quinazolinones through Copper-Catalyzed Multicomponent Reaction

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