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.

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“…These values indicate the reliability and predictive capability of the selected QSAR model in assessing compound activity. Additionally, validation metrics align with benchmark scores, meeting the criteria for an acceptable QSAR model, as suggested by Mouad Mouhsin and others[71][72][73].…”