World Journal of
Pharmaceutical and Life Sciences

An International Peer Reviewed Journal for Pharmaceutical and Life Sciences
An Official Publication of Society for Advance Healthcare Research (Reg. No. : 01/01/01/31674/16)
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Abstract

MONO, DI AND TRIKETO DERIVATIVES OF CHOLIC ACID AND THEIR HYPOGLYCEMIC EFFECTS

Tanja Šarenac* and Momir Mikov

ABSTRACT

Bile acids are amphiphilic molecules, which consist of a hydrophobic and a rigid steroid nucleus to which they are attached a hydrophilic hydroxyl groups, as well as flexible aliphatic acid side chain. The number, position and orientation of hydroxyl groups in the bile acid molecules may vary. The steroidal core of bile acids constitutes a saturated cyclopentanoperhydrophenanthrene hydrocarbon skeleton, consisting of three six-member (A, B, C) and one five-membered ring (D). Natural bile acids are derivatives of 5?-cholanic acid, wherein A and B rings are cislinked. The planar structure of amphiphilic bile acid, or the existence of a hydrophilic and hydrophobic surface molecule affects its physico-chemical characteristics and the ability to self-aggregation conditions. Monoketo derivatives of bile acids facilitate the permeability of the membrane. It has been shown that the 3?,7??dihydroxy?12?keto?5??cholanic acid exhibits hypoglycemic effect in diabetes type 1. Better effects are noted if mentioned 3?,7??dihydroxy?12?keto?5??cholanic acid is used in combination with hypoglycemic gliclazide or preparate of stevioside. The best effect in glycemic control was achieved when rats with type 1 diabetes were pretreated with probiotics, and then simultaneously with the use of a derivative of 3?,7??dihydroxy?12?keto?5??cholanic acid and gliclazide. The latest studies of diabetes in rodents in experimental models have shown that synthetic derivatives such as sodium 3?,7 ?dihydroxy?12?keto?5??cholanate results in the reduction of blood glucose concentration, which is the concentration reached 54% of that obtained following subcutaneous administration of the same dose of insulin. The aim of this paper is to explain the synthesis of various mono, di and tri keto derivatives of cholic acid, as well as to analyze the discovery of the association between bile acids (the most of 3?,7??dihydroxy?12?keto?5??cholanic acid) and glucose regulation, which gives us a new perspective in the design of hypoglycemic drugs in the treatment of diabetes.

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