Pemodelan Molekul, Sintesis dan Penentuan Aktivitas Antineoplastik 1-(4-Trifluorometilbenzoiloksi)Urea
Abstract: To design new drugs,
physical-chemical characteristics of drug molecules can be predicted by in
silico test before drugs are synthesized. Ribonucleotide reductase is the main
target or receptor of antineoplastic compounds such as hydroxyurea (HU) and its
derivatives like 1-(4-trifluoromethylbenzoyloxy)urea or 4-CF3BOU. This compound
forms a complex with crystal structure of ribonucleotide reductase I enzyme,
which is 2EUD. The hydrogen bond and bond energy in the form of rerank score
from both complexes was calculated with Molegro program. Theoretically,
compound activity is indicated by rerank score. The compound whose rerank score
is small is predicted to have greater activity. The activity of 4-CF3BOU was
found to be greater than HU. The reaction mechanism of synthesis 4-CF3BOU was
the substitution of nucleophilic hydroxyl group from HU to carbonyl group of
4–trifluoromethylbenzoyl chloride (4-CF3BCl). Purity test was conducted using
TLC and melting point. Structure identification was performed based on the
spectra of UV-VIS, FT-IR, H/C-NMR and MS. In this study, 4-CF3BOU was
discovered to have antineoplastic activity with the IC50 value of 82.37 μg/mL
and was tested towards HeLa cells. On the other hand, HU had the IC50 value of
430.21 μg/mL. The antineoplastic activity of 4-CF3BOU was greater than HU.
Kata kunci: 1-(4-trifluorometilbenzoiloksi)urea, uji in silico, sintesis,
uji aktivitas antineoplastik
Penulis: SUKO HARDJONO
Kode Jurnal: jpfarmasidd160447
