Synthesis, Photochemical and In Vitro Cytotoxic Evaluation of New Iodinated Aminosquaraines as Potential Sensitizers for Photodynamic Therapy
Filipa Mandim,
Vânia C. Graça,
Ricardo C. Calhelha,
Isabel L. F. Machado,
Luis F. V. Ferreira,
Isabel C.F.R. Ferreira,
Paulo F. Santos
Affiliations
Filipa Mandim
Centro de Química-Vila Real (CQ-VR), Universidade de Trás-os-Montes e Alto Douro, 5001-801 Vila Real, Portugal
Vânia C. Graça
Centro de Química-Vila Real (CQ-VR), Universidade de Trás-os-Montes e Alto Douro, 5001-801 Vila Real, Portugal
Ricardo C. Calhelha
Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal
Isabel L. F. Machado
CQFM-Centro de Química-Física Molecular and IN-Institute for Nanosciences and Nanotechnologies and IBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal
Luis F. V. Ferreira
CQFM-Centro de Química-Física Molecular and IN-Institute for Nanosciences and Nanotechnologies and IBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal
Isabel C.F.R. Ferreira
Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal
Paulo F. Santos
Centro de Química-Vila Real (CQ-VR), Universidade de Trás-os-Montes e Alto Douro, 5001-801 Vila Real, Portugal
In this work, several benzothiazole-based aminosquaraine dyes, displaying strong absorption within the so-called phototherapeutic window (650–800 nm), were synthesized. The ability, of all the new dyes, to generate singlet oxygen was assessed by determining the correspondent phosphorescence emission and through the comparison with a standard. The quantum yields of singlet oxygen generation were determined and exhibited to be strongly dependent on the nature of the amino substituents introduced in the squaric ring. The photodynamic activity of the synthesized dyes was tested against four human tumor cell lines: breast (MCF-7), lung (NCI-H460), cervical (HeLa) and hepatocellular (HepG2) carcinomas; and a non-tumor porcine liver primary cell culture (PLP2). All the compounds synthesized were found to be able to inhibit tumor cells growth upon irradiation more than in the dark, in most of the cases, very significantly. Considering the photodynamic activity exhibited and the low toxicity displayed for the non-tumor cells, some of the synthetized dyes can be regarded as potential candidates as photosensitizers for PDT.