Synthesis and Biological Evaluation of ...
Type de document :
Article dans une revue scientifique
PMID :
URL permanente :
Titre :
Synthesis and Biological Evaluation of N-[2-(4-Hydroxyphenylamino)-pyridin-3-yl]-4-methoxy-benzenesulfonamide (ABT-751) Tricyclic Analogues as Antimitotic and Antivascular Agents with Potent in Vivo Antitumor Activity
Auteur(s) :
Segaoula, Zacharie [Auteur]
Leclercq, Julien [Auteur]
Verones, Valerie [Auteur]
Flouquet, Nathalie [Auteur]
Lecoeur, Marie [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Ach, Lionel [Auteur]
Renault, Nicolas [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Barczyk, Amelie [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Melnyk, Patricia [Auteur]
Berthelot, Pascal [Auteur]
Thuru, Xavier [Auteur]
Lebegue, Nicolas [Auteur]
Leclercq, Julien [Auteur]
Verones, Valerie [Auteur]
Flouquet, Nathalie [Auteur]
Lecoeur, Marie [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Ach, Lionel [Auteur]
Renault, Nicolas [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Barczyk, Amelie [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Melnyk, Patricia [Auteur]
Berthelot, Pascal [Auteur]
Thuru, Xavier [Auteur]
Lebegue, Nicolas [Auteur]
Titre de la revue :
Journal of medicinal chemistry
Nom court de la revue :
J. Med. Chem.
Numéro :
59
Pagination :
8422-8440
Date de publication :
2016
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé :
Benzopyridothiadiazepine (2a) and benzopyridooxathiazepine (2b) were modified to produce tricyclic quinazolinone 15-18 or benzothiadiazine 26-27 derivatives. These compounds were evaluated in cytotoxicity and tubulin ...
Lire la suite >Benzopyridothiadiazepine (2a) and benzopyridooxathiazepine (2b) were modified to produce tricyclic quinazolinone 15-18 or benzothiadiazine 26-27 derivatives. These compounds were evaluated in cytotoxicity and tubulin inhibition assays and led to potent inhibitors of tubulin polymerization. N-[2(4-Methoxyphenyl)ethyl]-1,2-dihydro-pyrimidino[2,1-b]quinazolin-6-one (16a) exhibited the best in vitro cytotoxic activity (GI50 10-66.9 nM) against the NCI 60 human tumor cell line and significant potency against tubulin assembly (IC50 0.812 μM). In mechanism studies, 16a was shown to block cell cycle in G2/M phase and to disrupt microtubule formation and displayed good antivascular properties as inhibition of cell migration, invasion, and endothelial tube formation. Compound 16a was evaluated in C57BL/6 mouse melanoma B16F10 xenograft model to validate its antitumor activity, in comparison with reference ABT-751 (1). Compound 16a displayed strong in vivo antitumor and antivascular activities at a dose of 5 mg/kg without obvious toxicity, whereas 1 needed a 10-fold higher concentration to reach similar effects.Lire moins >
Lire la suite >Benzopyridothiadiazepine (2a) and benzopyridooxathiazepine (2b) were modified to produce tricyclic quinazolinone 15-18 or benzothiadiazine 26-27 derivatives. These compounds were evaluated in cytotoxicity and tubulin inhibition assays and led to potent inhibitors of tubulin polymerization. N-[2(4-Methoxyphenyl)ethyl]-1,2-dihydro-pyrimidino[2,1-b]quinazolin-6-one (16a) exhibited the best in vitro cytotoxic activity (GI50 10-66.9 nM) against the NCI 60 human tumor cell line and significant potency against tubulin assembly (IC50 0.812 μM). In mechanism studies, 16a was shown to block cell cycle in G2/M phase and to disrupt microtubule formation and displayed good antivascular properties as inhibition of cell migration, invasion, and endothelial tube formation. Compound 16a was evaluated in C57BL/6 mouse melanoma B16F10 xenograft model to validate its antitumor activity, in comparison with reference ABT-751 (1). Compound 16a displayed strong in vivo antitumor and antivascular activities at a dose of 5 mg/kg without obvious toxicity, whereas 1 needed a 10-fold higher concentration to reach similar effects.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CHU Lille
Inserm
CHU Lille
Inserm
Collections :
Équipe(s) de recherche :
Modélisation biopharmaceutique et pharmacocinétique
Date de dépôt :
2019-02-26T17:11:43Z