Hetero-substituted sulfonamido-benzamide hybrids as glucokinase activators: Design, synthesis, molecular docking and <i>in</i>-<i>silico</i> ADME evaluation

dc.contributor.authorKhadse, Saurabh C.
dc.contributor.authorAmnerkar, Nikhil D.
dc.contributor.authorDighole, Krushna S.
dc.contributor.authorDhote, Ashish M.
dc.contributor.authorPatil, Vikas R.
dc.contributor.authorLokwani, Deepak K.
dc.contributor.authorUgale, Vinod G.
dc.contributor.authorCharbe, Nitin B.
dc.contributor.authorChatpalliwar, Vivekanand A.
dc.date.accessioned2025-01-23T19:46:44Z
dc.date.available2025-01-23T19:46:44Z
dc.date.issued2020
dc.description.abstractA series of hetero-substituted sulphonamido-benzamide derivatives which can activate glucokinase (GK) were synthesized and screened in-vitro using Human GK activation assay and in-vivo following oral glucose tolerance test (OGIT) assays. All the molecules were docked into the active site of 1V4S receptor grid by XP docking method utilizing Schrodinger software to assess the binding interactions. Compounds 12 (EC50 = 495 nM) and 15 (EC50 = 522 nM), revealed maximum in-vitro GK activation. Selected compounds were subjected for in-vivo OGIT assay. The data revealed that same compounds 12 (135 mg/dL) showed maximum reduction in blood glucose level followed by compound 15 (142 mg/dL) at 120 min. The docking results as glide score, binding energy and interactions were reported and compounds with maximum pharmacological activity were studied precisely. In-silico ADME parameters, pharmacokinetic properties and toxicity studies were carried out and all compounds were found to have good bioavailability and nontoxic. Overall, the series of hetero-substituted sulphonamido-benzamide hybrids are safe and could be explored further for better therapeutic efficacy as GK activators. (C) 2020 Elsevier B.V. All rights reserved.
dc.description.funderUniversity Grant Commission, India
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.molstruc.2020.128916
dc.identifier.eissn1872-8014
dc.identifier.issn0022-2860
dc.identifier.urihttps://doi.org/10.1016/j.molstruc.2020.128916
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100314
dc.identifier.wosidWOS:000587467200057
dc.language.isoen
dc.revistaJournal of molecular structure
dc.rightsacceso restringido
dc.subjectGlucokinase
dc.subjectGlucokinase activator
dc.subjectSulfonamido-benzamides
dc.subjectDocking
dc.subjectADME
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleHetero-substituted sulfonamido-benzamide hybrids as glucokinase activators: Design, synthesis, molecular docking and <i>in</i>-<i>silico</i> ADME evaluation
dc.typeartículo
dc.volumen1222
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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