Design, Synthesis, Structure-Activity Relationship and Docking Studies of Novel Functionalized Arylvinyl-1,2,4-Trioxanes as Potent Antiplasmodial as well as Anticancer Agents
DC Field | Value | Language |
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dc.contributor.author | Tiwari M.K. | - |
dc.contributor.author | Coghi P. | - |
dc.contributor.author | Agrawal P. | - |
dc.contributor.author | Shyamlal B.R.K. | - |
dc.contributor.author | Jun Yang L. | - |
dc.contributor.author | Yadav L. | - |
dc.contributor.author | Peng Y. | - |
dc.contributor.author | Sharma R. | - |
dc.contributor.author | Yadav D.K. | - |
dc.contributor.author | Sahal D. | - |
dc.contributor.author | Kam Wai Wong V. | - |
dc.contributor.author | Chaudhary S. | - |
dc.date.available | 2020-07-20T03:35:13Z | - |
dc.date.created | 2020-06-12 | - |
dc.date.issued | 2020-07 | - |
dc.identifier.issn | 1860-7179 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/67592 | - |
dc.description.abstract | A novel series of synthetic functionalized arylvinyl-1,2,4-trioxanes (8 a–p) has been prepared and assessed for their in vitro antiplasmodial activity against the chloroquine-resistant Pf INDO strain of Plasmodium falciparum by using a SYBR green-I fluorescence assay. Compounds 8 g (IC50=0.051 μM; SI=589.41) and 8 m (IC50=0.059 μM; SI=55.93) showed 11-fold and >9-fold more potent antiplasmodial activity, respectively, as compared to chloroquine (IC50=0.546 μM; SI=36.63). Different in silico docking studies performed on many target proteins revealed that the most active arylvinyl-1,2,4-trioxanes (8 g and 8 m) showed dihydrofolate reductase (DHFR) binding affinities on a par with those of chloroquine and artesunate. The in vitro cytotoxic potentials of 8 a–p were also evaluated against human lung (A549) and liver (HepG2) cancer cell lines along with immortalized normal lung (BEAS-2B) and liver (LO2) cell lines. Following screening, five derivatives viz. 8 a, 8 h, 8 l, 8 m and 8 o (IC50=1.65–31.7 μM; SI=1.08–10.96) were found to show potent cytotoxic activity against (A549) lung cancer cell lines, with selectivity superior to that of the reference compounds artemisinin (IC50=100 μM), chloroquine (IC50=100 μM) and artesunic acid (IC50=9.85 μM; SI=0.76). In fact, the most active 4-naphthyl-substituted analogue 8 l (IC50=1.65 μM; SI >10) exhibited >60 times more cytotoxicity than the standard reference, artemisinin, against A549 lung cancer cell lines. In silico docking studies of the most active anticancer compounds, 8 l and 8 m, against EGFR were found to validate the wet lab results. In summary, a new series of functionalized aryl-vinyl-1,2,4-trioxanes (8 a–p) has been shown to display dual potency as promising antiplasmodial and anticancer agents. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | John Wiley and Sons Ltd | - |
dc.relation.isPartOf | ChemMedChem | - |
dc.title | Design, Synthesis, Structure-Activity Relationship and Docking Studies of Novel Functionalized Arylvinyl-1,2,4-Trioxanes as Potent Antiplasmodial as well as Anticancer Agents | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000537285500001 | - |
dc.identifier.doi | 10.1002/cmdc.202000045 | - |
dc.identifier.bibliographicCitation | ChemMedChem, v.15, no.13, pp.1216 - 1228 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85085868473 | - |
dc.citation.endPage | 1228 | - |
dc.citation.startPage | 1216 | - |
dc.citation.title | ChemMedChem | - |
dc.citation.volume | 15 | - |
dc.citation.number | 13 | - |
dc.contributor.affiliatedAuthor | Yadav D.K. | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | anticancer | - |
dc.subject.keywordAuthor | antiplasmodial | - |
dc.subject.keywordAuthor | artemisinin | - |
dc.subject.keywordAuthor | artesunate | - |
dc.subject.keywordAuthor | trioxane | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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