ABSTRACT
Backgrounds: Pinostrobin has the potential activity as an anticancer. However, its activity is still lower than the anticancer drugs on the market. To increase its activity, pinostrobin derivatives have been synthesized, namely pinostrobin propionate and pinostrobin butyrate, which are predicted to have better activity and lower toxicity than pinostrobin after being tested by in silico approach. So the compound deserves to be tested for its anticancer activity and selectivity on normal cells. Objective: This study aims to determine the anticancer activity of pinostrobin propionate and pinostrobin butyrate against the T47D breast cancer cell line and its selectivity against the Vero cell line. Methods: The cytotoxicity test which is anticancer activity test and its selectivity on normal cell were carried out using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The cells used were breast cancer cell line T47D and normal Vero cells. The test results were analyzed using a microplate reader with a wavelength of 570 nm. Results: From the analysis of anticancer activity on T47D cells, the IC50 values of pinostrobin, pinostrobin propionate, and pinostrobin butyrate were 2.93, 0.57, and 0.40 mM, respectively. While the results of the cytotoxicity test on Vero cells obtained the CC50 value of pinostrobin, pinostrobin propionate, pinostrobin butyrate was 1.27, 0.94, and 0.89 mM, respectively. So the SI value of pinostrobin (SI=0.4) is smaller than its derivatives (SI=1.7 and 2.2). Meanwhile, pinostrobin butyrate is more selective than pinostrobin propionate. Conclusions: It can be concluded that pinostrobin propionate and pinostrobin butyrate compounds have greater activity and selectivity than pinostrobin so these compounds are promising to be further developed as anticancer candidates.
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).
