Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Design and Synthesis of Novel 2-Acetamido, 6-Carboxamide Substituted Benzothiazoles as Potential BRAFV600E Inhibitors - In vitro Evaluation of their Antiproliferative Activity
Δημιουργός/Συγγραφέας:	Batsi, Yakinthi [EL] Αντωνοπούλου, Γεωργία[EN] Antonopoulou, Georgia Fotopoulou, Theano Koumaki, Kassandra Kritsi, Eftichia Potamitis, Constantinos Goulielmaki, Maria Skarmalioraki, Salomi Papalouka, Chara Poulou-Sidiropoulou, Eleni [EL] Κοσμίδου, Παρασκευή[EN] Kosmidou, Paraskevi Douna, Stavroula Vidali, Maria-Sofia Gkotsi, Eleni-Fani [EL] Χατζηιωάννου, Αριστοτέλης[EN] Chatziioannou, Aristotelis [EL] Σουλιώτης, Βασίλης Λ.[EN] Souliotis, Vassilis L. [EL] Πλέτσα, Βασιλική[EN] Pletsa, Vassiliki [EL] Παπαδόδημα, Όλγα[EN] Papadodima, Olga [EL] Ζουμπουρλής, Βασίλης[EN] Zoumpourlis, Vassilis [EL] Γεωργιάδης, Παναγιώτης[EN] Georgiadis, Panagiotis [EL] Ζερβού, Μαρία[EN] Zervou, Maria [EL] Πίντζας, Αλέξανδρος[EN] Pintzas, Alexander [EL] Κώστας, Ιωάννης Δ.[EN] Kostas, Ioannis D.
Εκδότης:	Wiley-VCH GmbH
Ημερομηνία:	2023-11-16
Γλώσσα:	Αγγλικά
ISSN:	1860-7179 1860-7187
DOI:	10.1002/cmdc.202300322
Άλλο:	37792577
Περίληψη:	The oncogenic BRAFV600E kinase leads to abnormal activation of the MAPK signaling pathway and thus, uncontrolled cellular proliferation and cancer development. Based on our previous virtual screening studies which issued 2-acetamido-1,3 benzothiazole-6-carboxamide scaffold as active pharmacophore displaying selectivity against the mutated BRAF, eleven new substituted benzothiazole derivatives were designed and synthesized by coupling of 2-acetamidobenzo[d]thiazole-6-carboxylic acid with the appropriate amines in an effort to provide even more efficient inhibitors and tackle drug resistance often developed during cancer treatment. All derived compounds bore the benzothiazole scaffold substituted at position-2 by an acetamido moiety and at position-6 by a carboxamide functionality, the NH moiety of which was further linked through an alkylene linker to a sulfonamido (or amino) aryl (or alkyl) functionality or a phenylene linker to a sulfonamido aromatic (or non-aromatic) terminal pharmacophore in the order -C6 H4 -NHSO2 -R or reversely -C6 H4 -SO2 N(H)-R. These analogs were subsequently biologically evaluated as potential BRAFV600E inhibitors and antiproliferative agents in several colorectal cancer and melanoma cell lines. In all assays applied, one analog, namely 2-acetamido-N-[3-(pyridin-2-ylamino)propyl]benzo[d]thiazole-6-carboxamide (22), provided promising results in view of its use in drug development.
Τίτλος πηγής δημοσίευσης:	ChemMedChem
Τόμος/Κεφάλαιο:	18
Τεύχος:	22
Θεματική Κατηγορία:	[EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) [EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry [EL] Χημική Βιολογία[EN] Chemical Biology [EL] Βιοχημεία[EN] Biochemistry [EL] Κυτταρολογία[EN] Cytology [EL] Βιοπληροφορική[EN] Bioinformatics [EL] Δομική Βιολογία[EN] Structural Biology
Λέξεις-Κλειδιά:	BRAFV600E inhibitors Benzothiazole Cancer In silico studies In vitro biological evaluation
EU Grant identifier:	MIS 5002398/NSRF MIS-5000432/European Union
Κάτοχος πνευματικών δικαιωμάτων:	© 2023 The Authors. ChemMedChem published by Wiley-VCH GmbH.
Όροι και προϋποθέσεις δικαιωμάτων:	This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202300322
Έχει σχέση με:	https://antibodies.cancer.gov/detail/CPTC-BRAF-6
Σημειώσεις:	Research Materials NCI CPTC Antibody Characterization Program
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο