title: Chlorin p6-Based Water-Soluble Amino Acid Derivatives as Potent Photosensitizers for Photodynamic Therapy.
abstract: The development of novel photosensitizer with high phototoxicity, low dark toxicity, and good water solubility is a challenging task for photodynamic therapy (PDT). A series of chlorin p6-based water-soluble amino acid conjugates were synthesized and investigated for antitumor activity. Among them, aspartylchlorin p6 dimethylester (7b) showed highest phototoxicity against melanoma cells with weakest dark toxicity, which was more phototoxic than verteporfin while with less dark toxicity. It also exhibited better in vivo PDT antitumor efficacy on mice bearing B16-F10 tumor than verteporfin. The biological assays revealed that 7b was localized in multiple subcellular organelles and could cause both cell necrosis and apoptosis after PDT in a dose-dependent manner, resulting in more effective cell destruction. As a result, 7b represents a promising photosensitizer for PDT applications because of its strong absorption in the phototherapeutic window, relatively high singlet oxygen quantum yield, highest dark toxicity/phototoxicity ratio, good water solubility, and excellent in vivo PDT antitumor efficacy.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Cell Biology, Second Military Medical University , 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, China.
authors.forename: Guiyan
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Pharmacy, Fujian University of Traditional Chinese Medicine , 1 Qiuyang Road, Fuzhou, 350122, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Fujian University of Traditional Chinese Medicine , 1 Qiuyang Road, Fuzhou, 350122, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Dong
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, China.
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Miao
authors.affiliation: Department of Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , 225 Changhai Road, Shanghai 200438, China.
authors.forename: Ningyang
authors.initials: N
authors.lastname: Jia
authors.affiliation: Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University , 32 Shangshan Road, Fujian 350007, China.
authors.forename: Zou
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University , 32 Shangshan Road, Fujian 350007, China.
authors.forename: Buhong
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, China.
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Second Military Medical University , 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, China.
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Yao
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014867:Water / Q000737:chemistry
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; D014867:Water; C072905:chlorin p6