title: Synthesis and in vitro anticancer activity of zinc(II) phthalocyanines conjugated with coumarin derivatives for dual photodynamic and chemotherapy.
abstract: The combination of photodynamic therapy and chemotherapy is a promising strategy to overcome growing problems in contemporary medicine, such as low therapeutic efficacy and drug resistance. Four zinc(II) phthalocyanine-coumarin conjugates were synthesized and characterized. In these complexes, zinc(II) phthalocyanine was used as the photosensitizing unit, and a coumarin derivative was selected as the cytostatic moiety; the two components were linked via a tri(ethylene glycol) chain. These conjugates exhibit high photocytotoxicity against HepG2 human hepatocarcinoma cells, with low IC50 values in the range of 0.014-0.044 μM. The high photodynamic activities of these conjugates are in accordance with their low aggregation tendency and high cellular uptake. One of these conjugates exhibits high photocytotoxicity and significantly higher chemocytotoxicity. The results clearly show that the two antitumor components in these conjugates work in a cooperative fashion. As shown by confocal microscopy, the conjugates can localize in the mitochondria and lysosomes, and one of the conjugates can also localize in the cell nuclei.
authors.affiliation: Fujian Engineering Research Center for Drugs and Diagnoses - Photodynamic Therapy, College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108 (P.R. China).
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Zhou
authors.forename: Lu-Bo
authors.initials: LB
authors.lastname: Meng
authors.forename: Qi
authors.initials: Q
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Zheng
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Zhang
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Liu
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Xue
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003374:Coumarins / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D054833:Isoindoles; D008027:Light; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009942:Organometallic Compounds / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D017967:Zinc Compounds
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine
keywords: chemotherapy; conjugation; coumarin; photodynamic therapy; phthalocyanine