Functionalized azirine based scaffolds as endothelin inhibitors for the selective anti-angiogenic activity

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dc.contributor.authorSingh, H.
dc.contributor.authorSatish, N.
dc.contributor.authorBabu, T.R.
dc.contributor.authorSingh, A.
dc.contributor.authorYadav, B.
dc.contributor.authorSingh, S.K.
dc.contributor.authorWahajuddin
dc.contributor.authorSiddiqui, M.I.
dc.contributor.authorJagavelu, K.
dc.contributor.authorSudhakar, G.
dc.date.accepted2024-05-16
dc.date.accessioned2025-07-03T15:10:58Z
dc.date.accessioned2025-07-10T13:00:31Z
dc.date.application2024-05-05
dc.date.available2025-07-03T15:10:58Z
dc.date.available2025-07-10T13:00:31Z
dc.date.issued2024-08-05
dc.date.updated2025-07-03T15:11:00Z
dc.descriptionNo
dc.description.abstractAnti-angiogenic therapy has long been used as an adjunct therapy for the resolution of tumor burden. The current findings describe the synthesis of novel marine-based azirine-containing compounds that exhibit anti-angiogenic mediated anti-tumor activity. Azirine-2-carboxylate inhibited HUVEC-mediated tubulogenesis without causing cell death in a dose-dependent manner. Ex-vivo CAM, in-vivo Matrigel implantation, and ear angiogenesis experiments have all shown that azirine-2-carboxylate effectively inhibits angiogenesis. Furthermore, azirine-2-carboxylate inhibits the migration of ECs without disrupting the preformed tubule network. Azirine-2-carboxylate had adequate intramuscular systemic exposure and inhibited tumor growth in a xenograft mouse model. DARTS analysis, competitive binding assay, and gene expression investigations revealed that azirine-2-carboxylate inhibits endothelin-1-mediated angiogenesis. Overall, the discovery of azirine-2-carboxylate demonstrated a potent inhibition of angiogenesis targeting ET1 and a possible application in anti-angiogenic therapy.
dc.identifier.citationSingh H, Satish N, Babu TR, et aL (2024) Functionalized azirine based scaffolds as endothelin inhibitors for the selective anti-angiogenic activity. European Journal of Medicinal Chemistry. 274: 116510
dc.identifier.doihttps://doi.org/10.1016/j.ejmech.2024.116510
dc.identifier.urihttps://bradscholars.brad.ac.uk/handle/10454/20504
dc.languageen
dc.language.isoen
dc.openaccess.statusrestrictedAccess
dc.rights.licenseUnspecified
dc.status.refereedYes
dc.subjectAzirines
dc.subjectAnti-angiogenic property
dc.subjectCancer
dc.subjectEndothelial cells
dc.subjectEndothelin 1 inhibitor
dc.titleFunctionalized azirine based scaffolds as endothelin inhibitors for the selective anti-angiogenic activity
dc.typeArticle
dc.type.versionNo full-text in the repository
dspace.entity.typePublication
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