Tetraphenylporphyrin derivatives possessing piperidine group as potential agents for photodynamic therapy.
Photodynamic therapy (PDT) is a noninvasive therapeutic and promising procedure in cancer treatment and has attracted considerable attention in recent years. In the present paper, 2-piperidinetetraphenylporphyrin derivatives (P1-P3) conjugated with different substituents (Cl, Me, MeO group) at phenyl position were synthesized via nucleophilic substitution of 2-nitroporphyrin copper derivatives with piperidine by refluxing under a nitrogen atmosphere and then demetalization. The combination of1H NMR,13C NMR and HR-MS was used to elucidate the identities of them. Their photophysical and photochemical properties, intracellular localization, cytotoxicity in vitro and in vivo against QBC-939 cells were investigated. They have absorption at wavelength about 650nm. All synthesized photosensitizers showed low dark cytotoxicity and comparable with that of hematoporphyrin monomethyl ether (HMME). And they were more phototoxic than HMME to QBC-939 cells in vitro. In bearing QBC-939 tumor BALB/c nude mice, when it treated with 5mg/kg dose of PS and laser light (650nm, 100J/cm2, 180mW/cm2), the growth of tumor was inhibited compared to the control group. Among them, P3 exhibited better photodynamic antitumor efficacy on BALB/c nude mice at lower concentration. These results indicate that P3 is a new potential antitumor photosensitizer in photodynamic therapy and deserves further investigation.
Department of pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai 201620, China.
Ping-Yong
PY
Liao
Department of pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai 201620, China.
Ying-Hua
YH
Gao
Department of pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai 201620, China.
Xin-Rong
XR
Wang
"411" Hospital, Shanghai 200081, China.
Lei-Lei
LL
Bao
"411" Hospital, Shanghai 200081, China.
Jun
J
Bian
Shanghai Xianhui Pharmaceutical Co. Ltd., Shanghai 200433, China.
Tai-Shan
TS
Hu
Shanghai Xianhui Pharmaceutical Co. Ltd., Shanghai 200433, China.
Mei-Zhen
MZ
Zheng
Shanghai Xianhui Pharmaceutical Co. Ltd., Shanghai 200433, China.
Yi-Jia
YJ
Yan
Department of pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai 201620, China. Electronic address: zlchen1967@qq.com.
Zhi-Long
ZL
Chen
D000818:Animals; D002460:Cell Line; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*
D017319:Photosensitizing Agents; D010880:Piperidines; D011166:Porphyrins; C409084:tetraphenylporphyrin
Photodynamic therapy; Photosensitizer; Tetraphenylporphyrin; Tumor