title: Structure activity relationship and optimization of N-(3-(2-aminothiazol-4-yl)aryl)benzenesulfonamides as anti-cancer compounds against sensitive and resistant cells.
abstract: We recently described a new family of bioactive molecules with interesting anti-cancer activities: the N-(4-(3-aminophenyl)thiazol-2-yl)acetamides. The lead compound of the series (1) displays significant anti-proliferative and cytotoxic activities against a panel of cancer cell lines, either sensitive or resistant to standard treatments. This molecule also shows a good pharmacological profile and high in vivo potency towards mice xenografts, without signs of toxicity on the animals. In the present article, we disclose the structure-activity relationships of this lead compound, which have provided clear information about the replacement of the acetamide function and the substitution pattern of the benzenesulfonamide ring. An improved high-yielding synthetic procedure towards these compounds has also been developed. Our drug design resulted in potency enhancement of 1, our new optimized lead compound being 19. These findings are of great interest to further improve this scaffold for the development of future clinical candidates.
authors.affiliation: Université Côte d'Azur, CNRS, Institut de Chimie de Nice UMR7272, 06108 Nice, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Ronco
authors.affiliation: Université Côte d'Azur, CNRS, Institut de Chimie de Nice UMR7272, 06108 Nice, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Millet
authors.affiliation: Université Côte d'Azur, INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe Biologie et Pathologie des cellules mélanocytaires: de la pigmentation cutanée au mélanome, 151 Route de Saint-Antoine, 06200 Nice, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Plaisant
authors.affiliation: Université Côte d'Azur, INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe Biologie et Pathologie des cellules mélanocytaires: de la pigmentation cutanée au mélanome, 151 Route de Saint-Antoine, 06200 Nice, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Abbe
authors.affiliation: Université Côte d'Azur, INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe Biologie et Pathologie des cellules mélanocytaires: de la pigmentation cutanée au mélanome, 151 Route de Saint-Antoine, 06200 Nice, France.
authors.forename: Nedra
authors.initials: N
authors.lastname: Hamouda-Tekaya
authors.affiliation: Université Côte d'Azur, INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe Biologie et Pathologie des cellules mélanocytaires: de la pigmentation cutanée au mélanome, 151 Route de Saint-Antoine, 06200 Nice, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Rocchi
authors.affiliation: Université Côte d'Azur, CNRS, Institut de Chimie de Nice UMR7272, 06108 Nice, France. Electronic address: benhida@unice.fr.
authors.forename: Rachid
authors.initials: R
authors.lastname: Benhida
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000096926:Benzenesulfonamides
chemical_list: D000970:Antineoplastic Agents; D013449:Sulfonamides; D000096926:Benzenesulfonamides
keywords: Autophagy and apoptosis; Cancer; Drug resistance; Lead optimization; Structure activity relationship; Thiazolyl-benzenesulfonamides