AN EXPLAINING THEORY FOR DIURETIC-INDUCED-DIABETES INCIDENCES

Pharmaceutical Science-Pharmaceutical Chemistry

Abstract

Many patients with hypertension are also suffering from Type II Diabetes Mellitus (TIIDM). Different studies argued the fact that if these patients can use Hydrochlorothiazide (HCTZ) group or not to treat hypertension as these diuretics are accused of with diuretic-induced diabetes especially Chlorthalidone and Bendroflumethiazide. As nothing is definite yet; in this paper, we are jotting down a new theory. In other words, we are seeking to study HCTZ interactions with sulfonylurea receptor Kir 6.2\SUR1 considering the chemical fact that HCTZ is also sulfonamide derivates like sulfonylurea drugs which are hypoglycemic agents used in the treatment of TIIDM. Therefore, we have studied in-silico 12 HCTZ compounds’ interactions with the binding site of sulfonylurea in its receptor Kir6.2\SUR1. Then, we compared the results to the interactions of Glibenclamide (GBM); a sulfonylurea agent, with the named receptor. As a result, three compounds of this family (Chlorthalidone 1-1, Bendroflumethiazide 4-1, Metolazone 6-1) had bound to Kir6.2\SUR1 receptor in the same binding site of GBM. The rest members were almost close to the GBM binding site. These findings may explain the adverse effect that chlorthalidone and Bendroflumethiazide are accused of with. We suggest that they are agonists for Kir6.1\SUR1 receptor, which results in decreasing insulin secretion from the pancreas which consequences with hyper-glycemia. On the other hand, our results confirm that developing new anti-hyperglycemia agents from HCTZ as a lead compound is also possible and promising.