title: Photodynamic characterization of amino acid conjugated 15(1)-hydroxypurpurin-7-lactone for cancer treatment.
abstract: This study aims to improve the photodynamic properties and biological effectiveness of 15(1)-hydroxypurpurin-7-lactone dimethyl ester (G2), a semisynthetic photosensitizer, for the PDT treatment of cancer. The strategy we undertook was by conjugating G2 with aspartic acid and lysine amino acid moieties. The photophysical properties, singlet oxygen generation, distribution coefficiency (Log D in octanol/PBS pH 7.4), and photostability of these analogues and their in vitro bioactivities such as cellular uptake, intracellular localization, and photoinduced cytotoxicity were evaluated. In addition, selected analogues were also investigated for their PDT-induced vasculature occlusion in the chick chorioallantoic membrane model and for their antitumor efficacies in Balb/C mice bearing 4T1 mouse mammary tumor. From the study, conjugation with aspartic acid improved the aqueous solubility of G2 without affecting its photophysical characteristics. G2-Asp showed similar in vitro and in vivo antitumor efficacies compared to the parent compound. Given the hydrophilic nature of G2-Asp, the photosensitizer is a pharmaceutically advantageous candidate as it can be formulated easily for systemic administration and has reduced risk of aggregation in vascular system.
authors: Cancer Research Initiatives Foundation (CARIF), Sime Darby Medical Centre , Subang Jaya, Selangor, Malaysia.
authors: Siang Hui
authors: SH
authors: Lim
authors: Mun Li
authors: ML
authors: Yam
authors: May Lynn
authors: ML
authors: Lam
authors: Fadzly Azhar
authors: FA
authors: Kamarulzaman
authors: Norazwana
authors: N
authors: Samat
authors: Lik Voon
authors: LV
authors: Kiew
authors: Lip Yong
authors: LY
authors: Chung
authors: Hong Boon
authors: HB
authors: Lee
mesh_terms: D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D007783:Lactones; D017319:Photosensitizing Agents; D011166:Porphyrins; D026082:Singlet Oxygen