title: Novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine fused chlorins as very active photodynamic agents for melanoma cells.
abstract: The development of new stable 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins with high absorption properties at 650 nm, and their impressive photosensitizer ability against melanotic and amelanotic cancer cells is described. Comparison between a diester-substituted chlorin with the corresponding dihydroxymethyl derivative demonstrated that the increased hydrophilicity of the latter is crucial to ensure nanomolar activity against melanoma cells. The new photosensitizer leads to death of human melanoma cells being both apoptosis and necrosis in equal parts involved in the treatment response. The dihydroxymethyl-chlorin was particularly active against human melanocytic melanoma A375 cells, which can be viewed as a solution to overcome the resistance of melanotic melanoma to photodynamic therapy.
authors.affiliation: Centro de Química and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal.
authors.forename: Nelson A M
authors.initials: NA
authors.lastname: Pereira
authors.affiliation: Biophysics Unit, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal; CIMAGO - Center of Investigation in Environment, Genetics and Oncobiology, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal; IBILI - Institute for Biomedical Imaging and Life Science, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Laranjo
authors.affiliation: Centro de Química and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Pineiro
authors.affiliation: Centro de Química and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal.
authors.forename: Arménio C
authors.initials: AC
authors.lastname: Serra
authors.affiliation: Biophysics Unit, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Santos
authors.affiliation: Biophysics Unit, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Teixo
authors.affiliation: Biophysics Unit, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal; CIMAGO - Center of Investigation in Environment, Genetics and Oncobiology, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal; IBILI - Institute for Biomedical Imaging and Life Science, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal.
authors.forename: Ana Margarida
authors.initials: AM
authors.lastname: Abrantes
authors.affiliation: CIMAGO - Center of Investigation in Environment, Genetics and Oncobiology, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal; Applied Molecular Biology, University Clinic of Haematology, Faculty of Medicine of University of Coimbra, Coimbra, Portugal.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Gonçalves
authors.affiliation: CIMAGO - Center of Investigation in Environment, Genetics and Oncobiology, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal; Applied Molecular Biology, University Clinic of Haematology, Faculty of Medicine of University of Coimbra, Coimbra, Portugal.
authors.forename: Ana Bela
authors.initials: AB
authors.lastname: Sarmento Ribeiro
authors.affiliation: Biophysics Unit, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Casalta-Lopes
authors.affiliation: Biophysics Unit, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal; CIMAGO - Center of Investigation in Environment, Genetics and Oncobiology, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal; IBILI - Institute for Biomedical Imaging and Life Science, Faculty of Medicine of University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-548 Coimbra, Portugal.
authors.forename: M Filomena
authors.initials: MF
authors.lastname: Botelho
authors.affiliation: Centro de Química and Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal. Electronic address: tmelo@ci.uc.pt.
authors.forename: Teresa M V D
authors.initials: TM
authors.lastname: Pinho e Melo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D015394:Molecular Structure; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; D011720:Pyrazoles
keywords: Amelanotic melanoma; Chlorins; Melanotic melanoma; Photodynamic therapy; Photosensitizer