SUKO HARDJONO (2012) MODIFIKASI STRUKTUR 1-(BENZOILOKSI)UREADAN HUBUNGAN KUANTITATIF STRUKTUR-AKTIVITAS SITOTOKSIKNYA. Disertasi thesis, UNIVERSITAS AIRLANGGA.

Preview	Text (ABSTRAK) gdlhub-gdl-s1-2013-hardjonosu-22076-6.ringk-.pdf Download (180kB) | Preview
	Text (FULLTEXT) 32902.pdf Restricted to Registered users only Download (2MB) | Request a copy

Abstract

Structure Modification of 1-(benzoyloxy)urea and quantitative structure cytotoxic-activity realationships have been conducted. The goal was to obtain quantitative structure cytotoxic-activity relationship equations derived from physicochemical parameters of the derivatives and their citotoxic activity against HeLa cells. The study was conducted in eight steps. First step was determining the lead compound, 1-(benzoyloxy)urea, which was carried out after in silico test, synthesis, and citotoxic activity test. The Second step was selecting the substitutuents that would be used in structure modification of 1-(benzoyloxy)urea, based on Topliss method for aromatic compounds. According to the method, the substituents that have been choosed were –Cl, -CH3, -OCH3, -t-C4H9, -CF3, -Br, and –F, all in para position against carbonyl, -Cl in ortho position, and two –Cl in ortho and para postition simultaneously. The third step was in silico test using Molegro Virtual Docker Computer Program to select the 1-(benzoyloxy)urea derivative(s) which would be synthesized. From the in silico test, the number of hydrogen bonding and the Rerank Score (RS)of each compounds were obtained. The fourth step was synthesis 1-(benzoyloxy)urea derivatives using modified Schotten-Baumann Method which was based on nucleophilic substitution reaction, each was reaction between hydroxyurea with substituted benzoyl chloride. The fifth step was analysis the purity of synthesized compounds by melting point test and TLC method. The structure of pure compounds were confirmed using data from UV, IR, 1H-NMR, 13C-NMR, and MS/GC-MS spectra. The sixth step was in vitro cytotoxic activity test of the compounds against HeLa cell lines, where IC50 values were determine using probit analysis. The seventh step was selecting physicochemical parameters that would be used to obtain quantitative structure cytotoxic-activity realationships of the 1-(benzoyloxy)urea derivatives. The selected parameters were consist of lipophilic parameters ClogP and #960;, electronic parameters : RS and #963;, and steric parameters : CMR and Es. The last step was determining the QSAR equation using SPSS computer program. The results were 10 (ten) equations with significant r values. There was also a linear correlation between in silico test (RS value) and in vitro activity test (IC50 Log (1/IC citotoxic activity): 50 (n = 10; r = 0,639; s= 0,0686; F = 5,520; sig.= 0,047) ) = - 0,016 RS - 3.26 From ten equations which were obtained, the selected equation was Log (1/IC: 50) = 0.160 #960;2 (n = 10; r = 0,933; s = 0,0405; F = 8,435; sig.= 0,019) - 0.381 #960; + 0.007 RS - 0.118 Es – 1.167 This study was concluded that 1-(benzoyloxy)urea derivatives will be potential as anticancer drug candidate, after pass some further research

Actions (login required)

View Item