Investigation of Anticancer Drug Activity 5-Fluorouracil and Some Analog Derivatives by QSAR: Theoretical Study

Abstract

Abstract Theoretical measurements of pharmaceutical compound 5-fluorouracil (5-FU) drug and some analogue derivatives were achieved by DFT method with B3LYP/6–311G as a standard basis set. Series of 5-FU derivatives have a different activities (the minimum effective concentration; C), were studied depending on geometrical properties. Then, the straight line equations (Y= a X ∓ b) and square root of correlation factor (R2) can be extracted by plot of effective concentration logarithm [log (1/C)] for 5–FU derivatives versus each one of geometrical properties. This matter led to correct the geometrical properties of 5-FU derivatives and formulating of quantitative structure activity relationship (QSAR) by Hansch model. The final general mathematical equation of QASR as a function of geometrical properties can be concluded by using wolfram alpha program, as empirical equation between theoretical activity and these properties of 5-FU derivatives. The empirical equation of QASR was tested by substitution a theoretical values of geometrical properties to extract theoretical activity of 5-FU derivatives. A high correlation factor between theoretical and particular activities (R2 = 0.9998) of derivatives made matter more acceptable to estimate the activity of new derivatives (synthesized or suggested). So, a new drugs of 5-FU derivatives as a pyrimidines were selected and the theoretical activities were calculated by QSAR–Hansch model as a function of the geometrical properties. The extracted results of a new derivatives shown how can the increase of minimum effective concentration in a new designed derivatives of 5-FU drug (as a starting martial).