title: Quantitative Structure-Cytotoxic Activity Relationship 1-(Benzoyloxy)urea and Its Derivative.
abstract: 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).
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia. suko.hardjono@yahoo.com.
authors.forename: Suko
authors.initials: S
authors.lastname: Hardjono
authors.forename: Siswandono
authors.initials: S
authors.lastname: Siswodihardjo
authors.forename: Purwanto
authors.initials: P
authors.lastname: Pramono
authors.forename: Win
authors.initials: W
authors.lastname: Darmanto
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014508:Urea