title: Isatin sulfonamides: potent caspases-3 and -7 inhibitors, and promising PET and SPECT radiotracers for apoptosis imaging.
abstract: Caspases-3 and -7 play an essential role in apoptosis. Isatin sulfonamides have been identified as potent inhibitors of these executing caspases. Besides pharmacological application, these compounds can also serve as recognition units to target caspases using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) when labeled with a positron or a gamma emitter. Fluorinated, alkylated, arylated isatin derivatives, in addition to derivatives modified with heterocycles, have been prepared in order to improve their binding potency, selectivity and metabolic stability. Structural optimization has led to stable, highly active inhibitors, which after labeling have been applied in PET studies in tumor mouse models and for first preclinical and clinical investigations with healthy human volunteers. The results support further development of such radiotracers for clinical apoptosis imaging.
authors.affiliation: Department of Chemistry, Faculty of Science, Silpakorn University, Sanam Chandra Palace Campus, Nakhon Pathom 73000, Thailand.
authors.forename: Panupun
authors.initials: P
authors.lastname: Limpachayaporn
authors.affiliation: Klinik für Nuklearmedizin, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Campus 1, D-48149 Münster, Germany.|European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-Universität Münster, Waldeyerstraße 15, D-48149 Münster, Germany.|Cells-in-Motion, Center of Excellence, Westfälische Wilhelms-Universität Münster, Waldeyerstraße 15, D-48149 Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-Universität Münster, Waldeyerstraße 15, D-48149 Münster, Germany.|Cells-in-Motion, Center of Excellence, Westfälische Wilhelms-Universität Münster, Waldeyerstraße 15, D-48149 Münster, Germany.|Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Haufe
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000737:chemistry* / Q000378:metabolism; D053179:Caspase 7 / Q000737:chemistry* / Q000378:metabolism; D061945:Caspase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007510:Isatin / Q000031:analogs & derivatives*; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011859:Radiography; D013329:Structure-Activity Relationship; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D061945:Caspase Inhibitors; D013424:Sulfanilamides; D000077145:Sulfanilamide; D007510:Isatin; D053148:Caspase 3; D053179:Caspase 7