Synthesis, biological evaluation and molecular modeling of a novel series of fused 1,2,3-triazoles as potential anti-coronavirus agents

Karypidou, Konstantina; Ribone, Sergio R.; Quevedo, Mario Alfredo; Persoons, Leentje; Pannecouque, Christophe; Helsen, Christine; Claessens, Frank; Dehaen, Wim

doi:10.1016/j.bmcl.2018.09.019

Cited by 76 publications

(58 citation statements)

References 20 publications

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“…Dehaen et al reported a novel library of fused 1,2,3-triazole derivatives against coronavirus 229E in HEL cells [85]. Structureactivity relationship studies showed that some compounds displayed moderate inhibitory activities in micromolar range without alterations of the normal cell morphology in confluent HEL cell cultures at concentrations up to 100 mM.…”

Section: Reviewsmentioning

confidence: 99%

“…Please cite this article in press as: Pillaiyar, T. et al Recent discovery and development of inhibitors targeting coronaviruses, Drug Discov Today (2020), https://doi.org/10.1016/j. drudis.2020.01.015Drug Discovery TodayFIGURE 12Dipeptidyl aldehyde bisulfite adduct inhibitors(84)(85)(86), replicase(87) and RNA synthesis inhibitors(88).www.drugdiscoverytoday.com 15Reviews KEYNOTE REVIEW…”

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confidence: 99%

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Recent discovery and development of inhibitors targeting coronaviruses

Pillaiyar

Meenakshisundaram²,

Manickam

2020

Drug Discovery Today

329

323

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Section: Reviewsmentioning

confidence: 99%

mentioning

confidence: 99%

Recent discovery and development of inhibitors targeting coronaviruses

Pillaiyar

Meenakshisundaram²,

Manickam

2020

Drug Discovery Today

329

323

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“…A series of fused 1,2,3-triazole heterocycles and their antiviral properties have been explored by Karypidou et al 126 All synthesised hybrids were tested against several types of viruses such as HIV (types 1 and 2), herpes simplex viruses (types 1, 1 TK -, and 2), adeno virus-2, coronavirus, and vaccinia virus and values were compared with the appropriate positive control drugs (zidovudine, brivudine, cidofovir, ganciclovir, acyclovir, alovudine, and Urtica dioica agglutinin, and zalcitabine). However, antiviral assays indicated that the majority of compounds had slight or no activity against selected viruses.…”

Section: Antiviral Activitymentioning

confidence: 99%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

614

289

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A B S T R A C TThe 1,2,3-triazole ring is a major pharmacophore system among nitrogen-containing heterocycles. These fivemembered heterocyclic motifs with three nitrogen heteroatoms can be prepared easily using 'click' chemistry with copper-or ruthenium-catalysed azide-alkyne cycloaddition reactions. Recently, the 'linker' property of 1,2,3-triazoles was demonstrated, and a novel class of 1,2,3-triazole-containing hybrids and conjugates was synthesised and evaluated as lead compounds for diverse biological targets. These lead compounds have been demonstrated as anticancer, antimicrobial, anti-tubercular, antiviral, antidiabetic, antimalarial, anti-leishmanial, and neuroprotective agents. The present review summarises advances in lead compounds of 1,2,3-triazolecontaining hybrids, conjugates, and their related heterocycles in medicinal chemistry published in 2018. This review will be useful to scientists in research fields of organic synthesis, medicinal chemistry, phytochemistry, and pharmacology. Chemistry: synthesis and properties of the 1,2,3-triazolesThe general synthetic route of 1,2,3-triazoles using click chemistry is described in Scheme 1A. The most popular route to 1,2,3-triazoles is Cu(I)-catalysed Huisgen 1,3-dipolar cycloaddition, which is the https://doi.

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“…Another class of drugs that is being considered for testing against COVID‐19, is the triazole antifungals, 100 namely posaconazole, itraconazole, and their modified derivatives. This is based on previous studies that have demonstrated potent antiviral activities for these compounds, against a wide array of coronaviridae members, including FCoV‐I, human coronavirus‐229E (HCoV‐229E), MERS‐CoV, and SARS‐CoV 101‐105 . While triazoles are widely used as antifungal agents owing to their inhibition of ergosterol synthesis, which is an essential component of fungal cell membranes, they have also been shown to possess antiviral activities that were attributed to their differential inhibitory actions on viral helicases, including coronavirus helicase, thereby interfering with viral replication 101,104 .…”

Section: The Lysosomotropic Activities Of Different Drugs Undergoing mentioning

confidence: 99%

The lysosome: A potential juncture between SARS‐CoV‐2 infectivity and Niemann‐Pick disease type C, with therapeutic implications

et al. 2020

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Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID‐19. By describing the life cycle of the newly emergent coronavirus, SARS‐CoV‐2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID‐19. Moreover, we propose that Niemann‐Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS‐CoV‐2, by highlighting key established features of the disorder that together result in an “unfavorable” host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID‐19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC‐like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID‐19.

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Synthesis, biological evaluation and molecular modeling of a novel series of fused 1,2,3-triazoles as potential anti-coronavirus agents

Cited by 76 publications

References 20 publications

Recent discovery and development of inhibitors targeting coronaviruses

Recent discovery and development of inhibitors targeting coronaviruses

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

The lysosome: A potential juncture between SARS‐CoV‐2 infectivity and Niemann‐Pick disease type C, with therapeutic implications

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