The mechanism of furosemide diuretic activity. The role of molecule hydrophobic segment

The purpose of research: to study the dependence between the quantity of hydrophobic segment of furosemide molecule and its pharmacology activity. The quantum chemical analysis was done using non&empirical method DFI B3LYP/6&311G. The calculation was done with a help of GAMESS program. The pharmacology researches were carried out on male WISTAR rats weighing 220-250 g. Animals were divided in two groups: first group included rats, which were injected with furosemide in a dose of 15 mcM/kg; 2nd group included rats injected with iodine&furosemide in equimolar dose. Structure calculation showed, that the injection of iodine atom in furan cycle of furosemide changes slightly charge and conformation characteristics of the main part of molecule. The iodine furosemide was synthesized from furosemide. Comparative assessment of urinative activity of both substances was made. Iodine furosemide in equimolar dose promoted significantly diuretic activity (1.8 times more) in comparison with furosemide. The isolation of sodium with impact of iodine&furosemide also increased diuretic activity practically twofold (1.9) then furosemide. The ion potassium acted the same compared to furosemide. The study showed, that hydrophobic segment of the molecule furosemide was one of the basic fragments of molecule, which provide its diuretic activity. The atom of iodine in furan cycle rose hydrophobic segment and iodine activity. The experiment showed, that when producing high active and select diuretic preparations, along with polar groups, which originate hydrogen links with water and protein the quantity of hydrophobic segment of molecule must be also considered.