Insulin-enhancing activity of a dinuclear vanadium complex: 5-chloro-salicylaldhyde ethylenediamine oxovanadium(V) and its permeability and cytotoxicity.
A new insulin-enhancing oxovanadium complex 5-chloro-salicylaldhyde ethylenediamine oxovanadium (V) ([V(2)O(2)(mu-O)(2)L(2)]) has been synthesized. The complex was characterized by a variety of physical methods, including X-ray crystallography. The X-ray diffraction analysis show a dinuclear complex of two six-coordinate vanadium centers doubly bridged by the oxygen atoms of the Schiff base ligand with a V(2)O(2) diamond core. The complex was administered intragastrically to STZ-diabetic rats for 2 weeks. The biological activity results show that the complex at the dose of 10.0 and 20.0 mg V kg(-1), could significantly decrease the blood glucose level and ameliorate impaired glucose tolerance in STZ-diabetic rats. That results suggested that the complex exerts an antidiabetic effect in STZ-diabetic rats. Furthermore, the complex ([V(2)O(2)(mu-O)(2)L(2)]) had permeability above 10(-5)cm/s. The experimental results suggested that the vanadium complex permeates via a passive diffusion mechanism. It was also suggested the complex with salen-type ligands has good lipophilic properties and better oral administration. The cytotoxicity of the complex ([V(2)O(2)(mu-O)(2)L(2)]) on Caco-2 cells was measured by a decrease of cell viability using the MTT assay suggesting that the chlorine atom at C4 of complex [V(2)O(2)(mu-O)(2)L(2)] increased cytotoxicity for vanadium complexes.
Xie
Ming-jin
MJ
Deparment of Chemistry, Yunnan University, Kunming 650091, China. xmj7193@yahoo.com.cn
Yang
Xiao-da
XD
Liu
Wei-ping
WP
Yan
Shi-ping
SP
Meng
Zhao-hui
ZH
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018938:Caco-2 Cells; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D014638:Vanadates / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014639:Vanadium / Q000493:pharmacokinetics / Q000494:pharmacology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D014639:Vanadium; D014638:Vanadates