Theoretical Study of Topological Indices for Maximum Half-Effective Dose (ED50) of Cephalosporin Derivatives

Abstract

Present study deals the development of a regression equation for the prediction of pharmacokinetic property viz- Half Maximal Effective Dose (ED50) by various steps of stepwise regression analysis. ED50 is important parameter for expressing effectiveness of a drug. 31 compounds of cephalosporin were selected for the study. 3D structures of these compounds were prepared with the help of Chem Sketch and saved as a mol file. Various 2D- indices like winer, detour, randic, harary, balban, schultz etc. molecular topological indices, topological distance indices T(N-N), T(N-S), T(N-O) and 3D-indices like 3D Morse indices, Sum of Keir-Hall electro topological state (Ss) were calculated with the help of Dragon software. The molecular refractivity mol calculated by Chem Sketch- Then a stepwise regression analysis between ED50 and selected indices was carried out by Microsoft excel software. Thus, a multilinear regression equation was developed. There occurs very strong correlation (R2 ) 0.983, Pearson product moment correlation coefficient, r2 (0.986) between predicted and observed values of ED50. With the help of derived regression model the presently available molecule can be modified to newer molecule with desired value of ED50. However, during the modification toxicity is also forced to be controlled or minimized.