[Synthesis, preliminary antigastrelcosis activity and the protective effect on acute liver injury of zinc chlorin E4].
OBJECTIVE
To study the synthesis of zinc chlorin e4(1), its experimental antigastrelcosis activity as well as the protection against acute liver injuries.


METHODS
Chlorin e6(3) was prepared through acidic and alkaline oxidative degradation using silkworm excrement crude chlorophyll extracts as starting material. Compound 1 was synthesized via Zn(OAc)2 complex action with Chlorin e4(2) which was prepared by refluxing 3 in pyridine. Gastric ulcers were induced by abdominal injection of 0.2% indomethacin at 20 mg.kg-1 in rats. The ulcer indexes and ulcer numbers in gastric mucosa were determined. Acute liver injuries were induced by abdominal injection of 0.3% thioacetamide (TAA) or 0.3% CCl4 at 20 mg.kg-1 in mice, and activities of SGPT in mice were determined.


RESULTS
Compound 1 is previously unknown. Compared with control group, abdominal administration of 1 at 100 mg.kg-1 reduced significantly the gastric ulcer index (P < 0.001) and the number of ulcer (P < 0.001) induced by indomethacin in rats. Abdominal administration of 1 at 100 mg.kg-1 x 3 exhibited marked inhibitory effects on elevated activities of SGPT induced by TAA (P < 0.02) or CCl4(P < 0.01) in mice.


CONCLUSIONS
These results show that 1 has significant protective effect against indomethacin-induced gastric lesion in rats and TAA or CCl4 induced acute liver injuries in mice. It is suggested that 1 may be a promising new drug candidate for antigastrelcosis and liver injury protection.
Yao
J Z
JZ
College of Pharmacy, Second Military Medical University, Shanghai 200433, China. yaojz@public9.sta.net.cn
Liu
J F
JF
Zhang
W N
WN
Zhou
Y J
YJ
Zhu
J
J
Lu
J G
JG
Wang
X Y
XY
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D002252:Carbon Tetrachloride Poisoning; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D007213:Indomethacin; D008297:Male; D051379:Mice; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy
D000897:Anti-Ulcer Agents; D011166:Porphyrins; C475446:chlorin e4; D007213:Indomethacin