Synthesis and Biological Evaluation of Pyrrolo[2,1‐<i>f</i>][1,2,4]triazine <i>C</i>‐Nucleosides with a Ribose, 2′‐Deoxyribose, and 2′,3′‐Dideoxyribose Sugar Moiety

Li, Qingfeng; Lescrinier, Eveline; Groaz, Elisabetta; Persoons, Leentje; Daelemans, Dirk; Herdewijn, Piet; Jonghe, Steven De

doi:10.1002/cmdc.201700657

Cited by 19 publications

(16 citation statements)

References 18 publications

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“…Cytostatic activity was evaluated in vitro on nine different types of human tumor cell lines: Capan-1, Hap1, HCT-116, and NCI-H460, as well as hematological tumors such as DND-41, HL-60, K-562, MM.1S and Z-138 as described previously [ 41 ]. All human tumor cell lines were acquired from the American Type Culture Collection (ATCC, Manassas, VA, USA), except for the DND-41 cell line which was purchased from the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ Leibniz-Institut, Braunschweig, Germany) and the Hap1 cell line which was purchased from Horizon Discovery (Waterbeach, UK).…”

Section: Methodsmentioning

confidence: 99%

Asymmetric Primaquine and Halogenaniline Fumardiamides as Novel Biologically Active Michael Acceptors

et al. 2018

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Novel primaquine (PQ) and halogenaniline asymmetric fumardiamides 4a–f, potential Michael acceptors, and their reduced analogues succindiamides 5a–f were prepared by simple three-step reactions: coupling reaction between PQ and mono-ethyl fumarate (1a) or mono-methyl succinate (1b), hydrolysis of PQ-dicarboxylic acid mono-ester conjugates 2a,b to corresponding acids 3a,b, and a coupling reaction with halogenanilines. 1-[bis(Dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) was used as a coupling reagent along with Hünig′s base. Compounds 4 and 5 were evaluated against a panel of bacteria, several Mycobacterium strains, fungi, a set of viruses, and nine different human tumor cell lines. p-Chlorofumardiamide 4d showed significant activity against Staphylococcus aureus, Streptococcus pneumoniae and Acinetobacter baumannii, but also against Candida albicans (minimum inhibitory concentration (MIC) 6.1–12.5 µg/mL). Together with p-fluoro and p-CF3 fumardiamides 4b,f, compound 4d showed activity against Mycobacterium marinum and 4b,f against M. tuberculosis. In biofilm eradication assay, most of the bacteria, particularly S. aureus, showed susceptibility to fumardiamides. m-CF3 and m-chloroaniline fumardiamides 4e and 4c showed significant antiviral activity against reovirus-1, sindbis virus and Punta Toro virus (EC50 = 3.1–5.5 µM), while 4e was active against coxsackie virus B4 (EC50 = 3.1 µM). m-Fluoro derivative 4a exerted significant cytostatic activity (IC50 = 5.7–31.2 μM). Acute lymphoblastic leukemia cells were highly susceptible towards m-substituted derivatives 4a,c,e (IC50 = 6.7–8.9 μM). Biological evaluations revealed that fumardiamides 4 were more active than succindiamides 5 indicating importance of Michael conjugated system.

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Section: Methodsmentioning

confidence: 99%

Asymmetric Primaquine and Halogenaniline Fumardiamides as Novel Biologically Active Michael Acceptors

et al. 2018

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“…Suitable synthetic procedures for the preparation of compounds 4-7 were previously described. 21 Compound 8 was synthesized according to a literature method reported by Seela et al 23 As shown in Scheme 1, nucleobase 13 was first silylated under standard conditions [bis(trimethylsilyl)acetamide (BSA) in anhydrous MeCN] at room temperature, and then reacted with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose 12 to afford glycosylated intermediate 13 with a 1'-β-configuration. Compound 14 was then converted into 7-chloro tubercidin derivative 8 upon treatment with methanolic ammonia in a sealed tube (120 °C, 24 h).…”

Section: Chemistrymentioning

confidence: 99%

“…For the C-nucleoside construction, we employed a similar synthetic strategy as that previously used for the synthesis of 4. 21 The lithium salt of thiomethyl substituted heterocycle 19 was coupled with protected ribonolactone 18, affording The same general strategy was used to synthesize L-C-nucleosides 10 and 11, as illustrated in Scheme 3. In this case, the synthetic route started from L-ribose, which was first reacted with methanol under Fischer glycosylation conditions to give 23 in 91% yield.…”

Section: Chemistrymentioning

confidence: 99%

“…In a previous study, cellular toxicity against specific immortalized cell lines was also observed for compounds 4-7. 21 On the other hand, the N-nucleoside congener 8 and the base chlorinated derivative of 2'-β-Me C-nucleoside 1 (compound 9) were found to be devoid of any significant antiviral activity, while exhibiting a CC 50 of 2.53 and 4.78 µM, respectively. It should be noted that the 7-chloro modified 2'-β-Me C-nucleoside 9 was more toxic than 1.…”

Section: Antiviral Activitymentioning

confidence: 99%

“…A detailed account of the synthesis and characterization of compounds 4-7 was previously reported. 21 4.1.1. 7-Deaza-7-chloroadenosine (8).…”

Section: General Informationmentioning

confidence: 99%

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Anti-norovirus activity of C7-modified 4-amino-pyrrolo[2,1-f][1,2,4]triazine C-nucleosides

Groaz

Rocha‐Pereira

et al. 2020

European Journal of Medicinal Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Recent updates on 1,2,3‐, 1,2,4‐, and 1,3,5‐triazine hybrids (2017–present): The anticancer activity, structure–activity relationships, and mechanisms of action

Dong

Jiang

Zhang

et al. 2022

Archiv der Pharmazie

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Cancer is one of the leading causes of death across the world, and the prevalence and mortality rates of cancer will continue to grow. Chemotherapeutics play a critical role in cancer therapy, but drug resistance and side effects are major hurdles to effective treatment, evoking an immediate need for the discovery of new anticancer agents. Triazines including 1,2,3-, 1,2,4-, and 1,3,5-triazine have occupied a propitious place in drug design and development due to their excellent pharmacological profiles. Mechanistically, triazine derivatives could interfere with various signaling pathways to induce cancer cell death. Hence, triazine derivatives possess potential in vitro and in vivo efficacy against diverse cancers. In particular, triazine hybrids are able to overcome drug resistance and reduce side effects.Moreover, several triazine hybrids such as brivanib (indole-containing pyrrolo[2,1-f ][1,2,4]triazine), gedatolisib (1,3,5-triazine-urea hybrid), and enasidenib (1,3, 5-triazine-pyridine hybrid) have already been available in the market. Accordingly, triazine hybrids are useful scaffolds for the discovery of novel anticancer chemotherapeutics. This review focuses on the anticancer activity of 1,2,3-, 1,2, 4-, and 1,3,5-triazine hybrids, together with the structure-activity relationships and mechanisms of action developed from 2017 to the present. The enriched structure-activity relationships may be useful for further rational drug development of triazine hybrids as potential clinical candidates.

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Synthesis and Biological Evaluation of Pyrrolo[2,1‐f][1,2,4]triazine C‐Nucleosides with a Ribose, 2′‐Deoxyribose, and 2′,3′‐Dideoxyribose Sugar Moiety

Cited by 19 publications

References 18 publications

Asymmetric Primaquine and Halogenaniline Fumardiamides as Novel Biologically Active Michael Acceptors

Asymmetric Primaquine and Halogenaniline Fumardiamides as Novel Biologically Active Michael Acceptors

Anti-norovirus activity of C7-modified 4-amino-pyrrolo[2,1-f][1,2,4]triazine C-nucleosides

Recent updates on 1,2,3‐, 1,2,4‐, and 1,3,5‐triazine hybrids (2017–present): The anticancer activity, structure–activity relationships, and mechanisms of action

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