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, F_count/F_table = 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.

• Periodical: Materials Science Forum (Volume 1068)
• Pages: 197-204
• DOI: https://doi.org/10.4028/p-k3a76r
• Online since: August 2022
• Authors: Chynthia Azhari Utri, Harno Dwi Pranowo*, Deni Pranowo
• Keywords: Anti-Cervical Cancer, DFT, QSAR

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