Research Journal of Pharmacology and Pharmacodynamics

I. E. Otuokere ¹, F. J. Amaku ¹

Affiliations
1 Department of Chemistry, Michael Okpara University of Agriculture, Umudike, NG

Abstract

4,4'-(1H-1,2,4-triazol-1-ylmethanediyl)dibenzonitrile (letrozole) is a highly potent and totally selective aromatase inhibitor used in treatment of early breast cancer in women who have experienced menopause (end of monthly menstrual periods) and who have had other treatments, such as radiation or surgery to remove the tumor. Conformational analysis studies of letrozole were based on Arguslab software. The molecular mechanics potential energy function wer evaluated in terms of energies associated with bonded interactions (bond length, bond angle and dihedral angle) as well as non-bonded interactions (Vander Waals and electrostatic). Surfaces were created to visualize excited state properties such as highest occupied molecular orbital's, lowest unoccupied molecular orbital's and electrostatic potential (ESP) mapped density. The steric energy for letrozole was calculated to be 0.116739 a.u. (73.255075 kcal/mol). The most energetically favourable conformation of letrozole was found to have a heat of formation of 1208.5864 kcal/mol. The self-consistent field (SCF) energy was calculated by geometry convergence function using RHF/AM1 method with a net charge of -1 and valence electron of 94 , in ArgusLab software. The most feasible position for letrozole to act as a highly potent and totally selective aromatase inhibitor was found to be -116.271466 au (-72961.512600 kcal/mol)

Keywords

Arguslab, Letrozole, Molecular Mechanics, Conformation Analysis, Aromatase Inhibitor.

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I. E. Otuokere ¹, F. J. Amaku ¹

Affiliations
1 Department of Chemistry, Michael Okpara University of Agriculture, Umudike, NG

Abstract

Dexrazoxane (4,4'-(2S)-propane-1,2-diyldipiperazine-2,6-dione) a cyclic derivative of edetic acid, is a site-specific cardioprotective agent that effectively protects against anthracycline-induced cardiac toxicity. Geometry optimization was performed using Arguslab software. The atomic coordinates, bond length, bond angles, dihedral angles, Muliken atomic charges, ZDO atomic charges and final steric energy evaluation of dexrazoxane were calculated. The highest occupied molecular orbitals, lowest unoccupied molecular orbital, electron clouds, and electrostatic potential mapped density surfaces were created. Heat of Formation of dexrazoxane was 622.179600 kcal/mol. The steric energy calculated for dexrazoxane was 0.026350 a.u. (16.535264 kcal/mol). SCF energy was found to be -129.162975 au (-81051.064000 kcal/mol) as calculated by RHF/AM1 method, performed by Argusl ab 4.0.1 suite. The SCF energy represents the most feasible energy where dexrazoxane would bind to the receptor for effective protection against anthracycline-induced cardiac toxicity.

Keywords

Arguslab Software, Dexrazoxane, Molecular Mechanics, in Silico, Geometry Optimization.

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