Journal of Molecular Modeling 2013-04-01

Pharmacophoric features of drugs with guanylurea moiety: an electronic structure analysis.

Yoganjaneyulu Kasetti, Prasad V Bharatam

Index: J. Mol. Model. 19(4) , 1865-74, (2013)

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Abstract

Several therapeutically important compounds contain guanylurea (GU) moiety. The appropriate tautomeric state of these species has not been explored, preliminary studies indicated that the traditional representation of this class of compounds use a high energy tautomeric state. In this work, quantum chemical studies (HF, B3LYP, MP2, G2MP2 and CBS-Q methods) were performed on the medicinally important GU based drugs so as to identify their stable tautomeric state and to understand the pharmacophoric features of these drugs. Electronic structure studies suggested that GU-1 is the most stable and preferred isomer among the various ketone and enol isomers of the model GU. This study revealed that the general representation adopted in medicinal chemistry literature (GU-5) is about 10 kcal mol(-1) less stable than the energy minimum tautomeric state; and four other alternate structures are possible with energy less than that of the generally represented structure. Hence, it is advisable to consider the energy minimum tautomeric state (GU-1) in all future studies of GU derivatives. Further, the importance of the correct tautomeric representation was demonstrated using a comparative molecular docking analysis of WHR 1049 in α2A adrenergic receptor target.