Designing Derivative Compounds of 4-Chlorophenyloxy N-Alkyl Phosphoramidates as Anti-Cervical Cancer Agents Based on QSAR Model

Abstract

Design of 4-chlorophenyloxy n-alkyl phosphoramidates derivative compounds as anti-cervical cancer agents using the QSAR model research was purposed to determine the best QSAR equation from 4-chlorophenyloxy N-alkyl phosphoramidates (3’-[4-fluoroaryl-(1,2,3-triazol-1-yl)]-3’-deoxythymidine) derivative compound and design a new compound of 4-chlorophenyloxy N-alkyl phosphoramidates derivative which has better activity than derivative compounds that synthesized before. Designing new anti-cervical cancer was done using electronic descriptor and molecular descriptor, which is obtained using DFT/ B3LYP/6-31G calculation. The linear regression method arranged the best QSAR equation and predicted the IC50. The best QSAR model to design the anti-cervical cancer compound is log IC50 = -498.629 + (-69.645 × qCl) + (-1267.348 × qC12) + (-25.627 × qC17) + (-1209.520 × qO4) + (0.541 × log P ), with statistic parameter n = 21, r2 = 0.867, SEE = 0,179, Fcount/Ftable = 6.758 external validation of QSAR equation, n = 5, r2 = 0.7302, PRESS = 1.798. The best compound is P-01 with the compound reference is PHO-016 (R1: 2-COCH3-Ph and R2: CF3CH2): 3’-[4-(2-acetylphenyl)-(1,2,3-triazol-1-yl)]-3’-deoxythymidine 5’-O-[4-chlorophenyl N-(2,2,2-trifluoroethyl)phosphate] who has IC50: -10.693 and log P: 2.450. The result can be the best suggestion for anti-cervical cancer candidates with better biology activity and can enter the membrane cell.