Targeted design, synthesis, molecular dynamics, ADME and in –vitro anticancer assessment of oxo-tetrahydro-pyrimidin-benzenesulfonamide hybrids as potential BRAFV600E inhibitors
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Le résumé fourni par la source
BRAF mutations appear to varying degrees in human cancers. Proposed oxo-tetrahydro-pyrimidin-benzenesulfonamide hybrids target [αC-OUT/DFG-IN] conformation of BRAF V600E similar to second-generation FDA-approved drugs. Nine compounds (S1–S9) were synthesized and spectrally characterized using Mass, HRMS, 1 H, and 13 C NMR. All synthesized derivatives were tested for anti-proliferative activity against two cancer cell lines, and the percentage of BRAF V600E enzyme kinase inhibition was calculated using sorafenib as the standard. Molecular docking was performed for all compounds, while molecular dynamics simulations were conducted for the most active molecules, providing insights into their stability and interactions within the target binding site. The biological assay revealed that most compounds exhibited significant anticancer activity, with compound S4 demonstrating strong inhibition of the BRAF V600E kinase. Notably, S4 (91%) and S1 (87%) showed potent inhibitory effects, comparable to the reference drug, sorafenib (94%). Based on these promising results, S4 and S1 were selected for molecular dynamics simulations to elucidate their binding stability and conformational dynamics within the BRAF V600E active site. These findings highlight that these compounds may act as potential lead compounds for the development of BRAF V600E inhibitors.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Targeted design, synthesis, molecular dynamics, ADME and in –vitro anticancer assessment of oxo-tetrahydro-pyrimidin-benzenesulfonamide hybrids as potential BRAFV600E inhibitors
- Date Crossref
- 08/10/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Central University of Punjab Department of Pharmaceutical Sciences and Natural Products pays non établi dans la noticeUniversité ou école supérieure
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Sam Higginbottom Institute of Agriculture pays non établi dans la noticeOrganisme public
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GITAM University pays non établi dans la noticeUniversité ou école supérieure
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Qassim University pays non établi dans la noticeUniversité ou école supérieure
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King Abdullah University of Science and Technology Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC) pays non établi dans la noticeUniversité ou école supérieure
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Ruđer Bošković Institute Center for Informatics and Computing pays non établi dans la noticeStructure de recherche
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Sam Higginbottom University of Agriculture Bioorganic and Medicinal Chemistry Research Laboratory pays non établi dans la noticeUniversité ou école supérieure
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School of Pharmacy Department of Pharmaceutical Analysis pays non établi dans la noticeUniversité ou école supérieure
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College of Pharmacy Department of Pharmaceutical Chemistry and Pharmacognosy pays non établi dans la noticeUniversité ou école supérieure
Department of Pharmaceutical Sciences and Natural Products — Central University of Punjab, Sam Higginbottom Institute of Agriculture et GITAM University, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.