Drug development is originally carried out on a trial and error basis and it is cost-prohibitive. To minimize the trial and error risks, drug design is needed. One of the compound development processes to get a new drug is by designing a structure modification of the mother compound whose activities are recognized. A substitution of the mother compounds alters the physicochemical properties: lipophilic, electronic and steric properties. In Indonesia, one of medical treatments to cure cancer is through chemotherapy and hydroxyurea. Some derivatives, phenylthiourea, phenylurea, benzoylurea, thiourea and benzoylphenylurea, have been found to be anticancer drug candidates. To predict the activity of the drug compound before it is synthesized, the in-silico test is required. From the test, Rerank Score which is the energy of interaction between the receptor and the ligand molecule is then obtained. Hydroxyurea derivatives were synthesized by modifying Schotten-Baumann’s method by the addition of benzoyl group and its homologs resulted in the increase of lipophilic, electronic and steric properties, and cytotoxic activity. Synthesized compounds were 1-(benzoyloxy)urea and its derivatives. Structure characterization was obtained by the spectrum of UV, IR, H NMR, C NMR and Mass Spectrometer. Anticancer activity was carried out using MTT method on HeLa cells. The Quantitative Structure-Cytotoxic Activity Relationships of 1-(benzoyloxy)urea compound and its derivatives was calculated using SPSS. The chemical structure was described, namely: ClogP, π, σ, RS, CMR and Es; while, the cytotoxic activity was indicated by log (1 / IC50). The results show that the best equation of Quantitative Structure-Cytotoxic Activity Relationships (QSAR) of 1- (benzoyloxy)urea compound and its derivatives is Log 1/IC50 = - 0.205 (+ 0.068) σ – 0.051 (+ 0.022) Es – 1.911 (+ 0.020)

Abstract.1 1-(Benzoyloxy)urea and its derivatives were synthesized by modified Scotten-Bauman reaction with adding benzoyl chloride or homologs to hydroxyurea in tetrahydrofuran. Structure characterization was conducted based on ultra-violet (UV-VIS) spectrum, infrared (FT-IR), H nucleus magnetic resonance ( 1 H NMR), C nuclear magnetic resonance ( 13 C NMR) and mass spectrometry (MS). In silico test to predict anti-cancer activity of 1-(benzoyloxy)urea and its derivatives in ribonucleotide reductase enzyme (PDB: 2EUD) was done using Molegro Program. The anti-cancer activity test was performed in vitro by using MTT method to HeLa cell lines. In silico test result (Rerank Score) was correlated relative to anti-cancer activity (log1/IC 50 ). There was a significant linear relationship between in vitro and in silico anti-cancer activity.