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dc.contributor.authorFelicetti, T
dc.contributor.authorBurali, MS
dc.contributor.authorGwee, CP
dc.contributor.authorKi Chan, KW
dc.contributor.authorAlonso, S
dc.contributor.authorMassari, S
dc.contributor.authorSabatini, S
dc.contributor.authorTabarrini, O
dc.contributor.authorBarreca, ML
dc.contributor.authorCecchetti, V
dc.contributor.authorVasudevan, SG
dc.contributor.authorManfroni, G
dc.description.abstractThe mosquito-borne viruses belonging to the genus Flavivirus such as Dengue virus (DENV) and Zika virus (ZIKV) cause human infections ranging from mild flu-like symptoms to hemorrhagic fevers, hepatitis, and neuropathies. To date, there are vaccines only for few flaviviruses while no effective treatments are available. Pyridobenzothiazole (PBTZ) derivatives are a class of compounds endowed with a promising broad-spectrum anti-flavivirus activity and most of them have been reported as potent inhibitors of the flaviviral NS5 polymerase. However, synthesis of PBTZ analogues entails a high number of purification steps, the use of hazardous reagents and environmentally unsustainable generation of waste. Considering the promising antiviral activity of PBTZ analogues which require further exploration, in this work, we report the development of a new and sustainable three-component reaction (3CR) that can be combined with a basic hydrolysis in a one-pot procedure to obtain the PBTZ scaffold, thus reducing the number of synthetic steps, improving yields and saving time. 3CR was significantly explored in order to demonstrate its wide scope by using different starting materials. In addition, taking advantage of these procedures, we next designed and synthesized a new set of PBTZ analogues that were tested as anti-DENV-2 and anti-ZIKV agents. Compound 22 inhibited DENV-2 NS5 polymerase with an IC50 of 10.4 μM and represented the best anti-flavivirus compound of the new series by inhibiting DENV-2- and ZIKV-infected cells with EC50 values of 1.2 and 5.0 μM, respectively, that translates into attractive selectivity indexes (SI - 83 and 20, respectively). These results strongly reaffirm PBTZ derivatives as promising anti-flavivirus agents that now can be synthesized through a convenient and sustainable 3CR in order to obtain more potent compounds for further pre-clinical development studies.en_US
dc.publisherElsevier BVen_US
dc.relation.ispartofjournalEuropean Journal of Medicinal Chemistryen_US
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistryen_US
dc.subject.fieldofresearchOrganic Chemistryen_US
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciencesen_US
dc.subject.keywordsAntiviral agentsen_US
dc.subject.keywordsDengue inhibitorsen_US
dc.subject.keywordsNS5 polymeraseen_US
dc.subject.keywordsOne-pot procedureen_US
dc.subject.keywordsThree-component reaction (3CR)en_US
dc.titleSustainable, three-component, one-pot procedure to obtain active anti-flavivirus agentsen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Articlesen_US
dcterms.bibliographicCitationFelicetti, T; Burali, MS; Gwee, CP; Ki Chan, KW; Alonso, S; Massari, S; Sabatini, S; Tabarrini, O; Barreca, ML; Cecchetti, V; Vasudevan, SG; Manfroni, G, Sustainable, three-component, one-pot procedure to obtain active anti-flavivirus agents, European Journal of Medicinal Chemistry, 2021, 210, pp. 112992en_US
gro.hasfulltextNo Full Text
gro.griffith.authorVasudevan, Subhash

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