title: Quantitative and site-directed chemical modification of hypocrellins toward direct drug delivery and effective photodynamic activity.
abstract: For photodynamic therapy (PDT) treatment of microvascular diseases, drugs are delivered via blood circulation and the targets are vasculature endothelial cells, for which the contradictory requirements of hydrophilicity and lipophilicity of the drugs have been achieved by liposome preparations. Herein, it is demonstrated that the drug delivery and target affinity are achieved by a single chemical compound, hypocrellin B (HB) derivative 6 selected from three novel aminoalkanesulfonic acid HB derivatives, 5-7. 6 exhibits a much higher PDT activity (IC(50) = 22 nM) on human gastric carcinoma BGC823 cells than HB, while it has no cellular toxicity in the dark. On the basis of estimation of the clinically required concentration according to relative PDT activity and clinical criteria, it can be predicted that 6 is directly deliverable to and PDT effective on target cells. The enhanced red absorption and superhigh photoactivity suggest that 6 is more powerful for PDT of tumors than HB.
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Deng
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Xie
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
authors.forename: Naiyan
authors.initials: N
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Gu
authors.forename: Jingquan
authors.initials: J
authors.lastname: Zhao
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005453:Fluorescence; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008081:Liposomes; D010569:Perylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D026082:Singlet Oxygen / Q000737:chemistry; D012995:Solubility; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D008081:Liposomes; D017319:Photosensitizing Agents; D011809:Quinones; D013451:Sulfonic Acids; D026082:Singlet Oxygen; D010569:Perylene; C064522:hypocrellin B