title: Discovery and Optimization of N-(4-(3-Aminophenyl)thiazol-2-yl)acetamide as a Novel Scaffold Active against Sensitive and Resistant Cancer Cells.
abstract: Cancer is the second cause of deaths worldwide and is forecasted to affect more that 22 million people in 2020. Despite dramatic improvement in its care over the last two decades, the treatment of resistant forms of cancer is still an unmet challenge. Thus, innovative and efficient treatments are still needed. In this context, we report herein the synthesis and the evaluation of a new class of bioactive molecules belonging to the N-(4-(3-aminophenyl(thiazol-2-yl)acetamide family. Structure-activity relationships could be driven and resulted in the discovery of lead compound 6b. The latter display high in vitro potency against both sensitive and resistant cancer cell lines on three models: melanoma, pancreatic cancer, and chronic myeloid leukemia (CML). 6b leads to cell death by concomitant induction of apoptosis and autophagy, shows good pharmacokinetic properties, and demonstrates a significant reduction of tumor growth in vivo on A375 xenograft model in mice.
authors: Institut de Chimie de Nice, Université Nice Sophia Antipoils, UMR UNS-CNRS 7272 , 06108 Nice Cedex 2, France.
authors: Antoine
authors: A
authors: Millet
authors: Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe Biologie et Pathologie des Cellules Mélanocytaires: De La Pigmentation Cutanée au Mélanome, INSERM, U1065 , Parc Valrose, 06108 Nice Cedex 2, France.|UFR de Médecine, Université de Nice Sophia Antipolis , 06107 Nice, France.
authors: Magali
authors: M
authors: Plaisant
authors: Institut de Chimie de Nice, Université Nice Sophia Antipoils, UMR UNS-CNRS 7272 , 06108 Nice Cedex 2, France.
authors: Cyril
authors: C
authors: Ronco
authors: Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe Biologie et Pathologie des Cellules Mélanocytaires: De La Pigmentation Cutanée au Mélanome, INSERM, U1065 , Parc Valrose, 06108 Nice Cedex 2, France.|UFR de Médecine, Université de Nice Sophia Antipolis , 06107 Nice, France.
authors: Michaël
authors: M
authors: Cerezo
authors: Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe Biologie et Pathologie des Cellules Mélanocytaires: De La Pigmentation Cutanée au Mélanome, INSERM, U1065 , Parc Valrose, 06108 Nice Cedex 2, France.|UFR de Médecine, Université de Nice Sophia Antipolis , 06107 Nice, France.
authors: Patricia
authors: P
authors: Abbe
authors: Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe Biologie et Pathologie des Cellules Mélanocytaires: De La Pigmentation Cutanée au Mélanome, INSERM, U1065 , Parc Valrose, 06108 Nice Cedex 2, France.|UFR de Médecine, Université de Nice Sophia Antipolis , 06107 Nice, France.
authors: Emilie
authors: E
authors: Jaune
authors: Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe Biologie et Pathologie des Cellules Mélanocytaires: De La Pigmentation Cutanée au Mélanome, INSERM, U1065 , Parc Valrose, 06108 Nice Cedex 2, France.|UFR de Médecine, Université de Nice Sophia Antipolis , 06107 Nice, France.
authors: Elisa
authors: E
authors: Cavazza
authors: Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe Biologie et Pathologie des Cellules Mélanocytaires: De La Pigmentation Cutanée au Mélanome, INSERM, U1065 , Parc Valrose, 06108 Nice Cedex 2, France.|UFR de Médecine, Université de Nice Sophia Antipolis , 06107 Nice, France.|Service de Dermatologie, Hôpital Archet II, CHU , 06200 Nice, France.
authors: Stéphane
authors: S
authors: Rocchi
authors: Institut de Chimie de Nice, Université Nice Sophia Antipoils, UMR UNS-CNRS 7272 , 06108 Nice Cedex 2, France.
authors: Rachid
authors: R
authors: Benhida
mesh_terms: D000081:Acetamides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000081:Acetamides; D000970:Antineoplastic Agents; D013844:Thiazoles