Sustainable, three-component, one-pot procedure to obtain active anti-flavivirus agents

Felicetti, Tommaso; Burali, Maria Sole; Gwee, Chin Piaw; Chan, Kitti Wing Ki; Alonso, Sylvie; Massari, Serena; Sabatini, Stefano; Tabarrini, Oriana; Barreca, Maria Letizia; Cecchetti, Violetta; Vasudevan, Subhash G.; Manfroni, Giuseppe

doi:10.1016/j.ejmech.2020.112992

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…Therefore, we compiled a dataset of known DENV RdRp inhibitors from PubChem and the literature. In total, 94 compounds were obtained from several bioassays on PubChem AID: 441537 [20], 642356 [21], 663478 [22], 1277364 [23], 1301573 [24], 1401288 [25], 1401306 [25], 1497239 [26], 1655471 [27], 1674514 [28], 1728708 [29] and 30 compounds were manually collected from published studies [17,20,21,23,25,27,28,[30][31][32][33][34][35][36][37][38][39][40][41], providing a dataset of 124 DENV RdRp inhibitors. The in-house dataset from the Laboratory of Antibiotics and Chemotherapeutics (LAC), at São Paulo State University (UNESP), presents 77 natural and semi-synthetic compounds was merged to the publicly available dataset and a chemical space analysis was conducted using the dimensionality reduction method t-Distributed Stochastic Neighbor Embedding (t-SNE) [42].…”

Section: Chemical Space Analysis Of Rdrp Inhibitorsmentioning

confidence: 99%

Natural Compounds as Non-Nucleoside Inhibitors of Zika Virus Polymerase through Integration of In Silico and In Vitro Approaches

et al. 2022

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Although the past epidemic of Zika virus (ZIKV) resulted in severe neurological consequences for infected infants and adults, there are still no approved drugs to treat ZIKV infection. In this study, we applied computational approaches to screen an in-house database of 77 natural and semi-synthetic compounds against ZIKV NS5 RNA-dependent RNA-polymerase (NS5 RdRp), an essential protein for viral RNA elongation during the replication process. For this purpose, we integrated computational approaches such as binding-site conservation, chemical space analysis and molecular docking. As a result, we prioritized nine virtual hits for experimental evaluation. Enzymatic assays confirmed that pedalitin and quercetin inhibited ZIKV NS5 RdRp with IC50 values of 4.1 and 0.5 µM, respectively. Moreover, pedalitin also displayed antiviral activity on ZIKV infection with an EC50 of 19.28 µM cell-based assays, with low toxicity in Vero cells (CC50 = 83.66 µM) and selectivity index of 4.34. These results demonstrate the potential of the natural compounds pedalitin and quercetin as candidates for structural optimization studies towards the discovery of new anti-ZIKV drug candidates.

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Section: Chemical Space Analysis Of Rdrp Inhibitorsmentioning

confidence: 99%

Natural Compounds as Non-Nucleoside Inhibitors of Zika Virus Polymerase through Integration of In Silico and In Vitro Approaches

et al. 2022

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“…This innovative approach allows for the integration of a basic hydrolysis step within a single reaction vessel, streamlining the process and minimizing the need for multiple synthetic steps. By employing a benzothiazole acetate 3, N,N-dimethylformamide dimethyl acetal (DMF-DMA), and an anhydride 58 (as outlined in Scheme 26), this reaction not only enhances yields but also significantly reduces the overall reaction time, presenting a more efficient and sustainable route to the pyridobenzothiazole scaffold [69].…”

Section: Scheme 25mentioning

confidence: 99%

Chemistry and Biological Activities of Ethyl-2-benzothiazolyl Acetate and its Corresponding Hydrazides

Azzam,

Seif

2024

Advances in Basic and Applied Sciences

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This review article explores the synthesis and diverse reactions of ethyl-2-benzothiazolyl acetate and its corresponding hydrazide derivatives. The study presents a comprehensive investigation into various synthetic methodologies, demonstrating the versatility of these compounds in generating diverse chemical entities. The synthesis of ethyl-2-benzothiazolyl acetate involves several methods, including reactions with 2-aminothiophenol, ethyl cyanoacetate, ethyl ethoxycarbonylacetimidate hydrochloride, and diethyl malonate. Additionally, cyanomethylene benzothiazole can be converted to ethyl-2-benzothiazolyl acetate. These methods offer various pathways to achieve the desired compound with notable yields. Furthermore, detailed synthesis of 2-benzothiazolyl acetohydrazide from ethyl-2-benzothiazolyl acetate through reactions with hydrazine hydrate or by reacting 2-aminothiophenol with cyanoacetohydrazide was also descried. The subsequent derivatization of 2benzothiazolyl acetohydrazide and its derivatives through various reactions highlights the potential for creating diverse chemical scaffolds. The study explores the reactions of these compounds with various reagents, including aromatic aldehydes, 1,2,4-triazole, cinnamyl alcohol, hydroxybenzaldehyde, and more. The resulting compounds exhibit a range of structural and functional diversity. Moreover, the review systematically examines the diverse biological activities demonstrated by these compounds. The exploration of these activities extends to their potential applications in various fields, such as pharmaceuticals, and materials science. Additionally, the synthesis of fluorescent sensors and potential inhibitors for enzymes is discussed.

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“…HeE1-2Tyr (1) was originally identified by Tarantino et al [20] as a potent inhibitor of RdRp from all members of the genus Orthoflavivirus [20][21][22][23] and was crystallized in complex with the RdRp from DENV-3 [20]. In 2021, our group reported this compound to also exhibit inhibitory activity against feline infectious peritonitis virus (FIPV) and SARS-CoV-2 RdRp and to hinder viral replication in cell-based antiviral assays [24].…”

Section: Introductionmentioning

confidence: 99%

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

Tóth,

Krejčová,

Dejmek

et al. 2024

Beilstein J. Org. Chem.

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The RNA-dependent RNA polymerase (RdRp) represents a prominent target in the discovery and development of new antivirotics against RNA viruses, inhibiting the replication process. One of the most targeted RNA viruses of the last years is, without doubt, SARS-CoV-2, the cause of the recent COVID-19 pandemic. HeE1-2Tyr, a known inhibitor of flaviviral RdRp, has been discovered to also have antiviral potency against this coronavirus. In this study, we report three distinct modifications of HeE1-2Tyr: conversion of the core from a benzothiazole to a benzoxazole moiety and two different scaffold simplifications, respectively. We provide a novel synthetic approach and, in addition, evaluate the final molecules in an in vitro polymerase assay for biological activity.

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Sustainable, three-component, one-pot procedure to obtain active anti-flavivirus agents

Cited by 8 publications

References 26 publications

Natural Compounds as Non-Nucleoside Inhibitors of Zika Virus Polymerase through Integration of In Silico and In Vitro Approaches

Natural Compounds as Non-Nucleoside Inhibitors of Zika Virus Polymerase through Integration of In Silico and In Vitro Approaches

Chemistry and Biological Activities of Ethyl-2-benzothiazolyl Acetate and its Corresponding Hydrazides

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

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