Hydrazone-Functionalized trans -A 2 B-Corroles: Effective Synergy in Photodynamic Therapy of Lung Cancer.

Autor:	Costa BDP; University of Coimbra, Coimbra Chemistry Centre-Institute of Molecular Sciences (CQC-IMS) and Department of Chemistry, 3004-535 Coimbra, Portugal., Simões JCS; University of Coimbra, Coimbra Chemistry Centre-Institute of Molecular Sciences (CQC-IMS) and Department of Chemistry, 3004-535 Coimbra, Portugal., Lopes SMM; University of Coimbra, Coimbra Chemistry Centre-Institute of Molecular Sciences (CQC-IMS) and Department of Chemistry, 3004-535 Coimbra, Portugal., Laranjo M; University of Coimbra, Faculty of Medicine, Biophysics Institute, 3000-370 Coimbra, Portugal.; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) area of Environment Genetics and Oncobiology (CIMAGO), 3000-548 Coimbra, Portugal.; University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal., Rodrigues ACB; University of Coimbra, Coimbra Chemistry Centre-Institute of Molecular Sciences (CQC-IMS) and Department of Chemistry, 3004-535 Coimbra, Portugal., Gonçalves AC; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) area of Environment Genetics and Oncobiology (CIMAGO), 3000-548 Coimbra, Portugal.; University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal.; University of Coimbra, Faculty of Medicine, Laboratory of Oncobiology and Hematology (LOH), 3000-548 Coimbra, Portugal., Seixas de Melo JS; University of Coimbra, Coimbra Chemistry Centre-Institute of Molecular Sciences (CQC-IMS) and Department of Chemistry, 3004-535 Coimbra, Portugal., Botelho MF; University of Coimbra, Faculty of Medicine, Biophysics Institute, 3000-370 Coimbra, Portugal.; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR) area of Environment Genetics and Oncobiology (CIMAGO), 3000-548 Coimbra, Portugal.; University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal., Pineiro M; University of Coimbra, Coimbra Chemistry Centre-Institute of Molecular Sciences (CQC-IMS) and Department of Chemistry, 3004-535 Coimbra, Portugal., Pinho E Melo TMVD; University of Coimbra, Coimbra Chemistry Centre-Institute of Molecular Sciences (CQC-IMS) and Department of Chemistry, 3004-535 Coimbra, Portugal.
Jazyk:	angličtina
Zdroj:	Journal of medicinal chemistry [J Med Chem] 2024 Dec 26; Vol. 67 (24), pp. 21934-21951. Date of Electronic Publication: 2024 Oct 04.
DOI:	10.1021/acs.jmedchem.4c01824
Abstrakt:	A synthetic route to trans -A 2 B-corroles combining the macrocyclic core with a hydrazone moiety, based on the reactivity of azoalkenes toward dipyrromethanes, has been established with the aim of developing a new class of photosensitizers for photodynamic therapy of lung cancer. The study of the photophysical properties of the novel macrocycles allowed the identification of photosensitizers with absorption within the phototherapeutic window and high singlet oxygen quantum yield. Relevant structure-photodynamic activity correlations were established by studying the new corroles-based photodynamic therapy (PDT) in human lung cancer cell lines (A549 and H1299). The methyl-hydrazone corroles were more active than phenyl-hydrazone corroles, with the N -Boc and N -Ts groups being key structural features to ensure high activity. The lead photosensitizers, with IC 50 values below 100 nM and no cytotoxicity per se, were significantly more active than 5,10,15-triphenylcorrole, showing that the presence of the hydrazone functional group has a strong influence on PDT activity.
Databáze:	MEDLINE
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