<span class="hps"><span lang="IN">Senyawa </span></span><em><span>N</span></em><span lang="IN">-</span><span>(</span><span lang="IN">b</span><span>enzo</span><span lang="IN">i</span><span>l)-<em>N</em>’-</span><span lang="IN">f</span><span>en</span><span lang="IN">i</span><span>ltiourea</span><span lang="IN"> mempunyai </span><span>gugus</span><span lang="IN"> farmakofor yang sama dengan turunan urea yang mempunyai aktivitas antikanker</span><span>, seperti</span><span>hidroksiurea, sehingga</span><span>layak</span><span>dijadikan</span><span>senyawa</span><span>induk</span><span>untuk</span><span>dikembangkan</span><span>lebih</span><span>lanjut</span><span>melalui</span><span>modifikasi</span><span>struktur</span><span class="hps"><span lang="IN">.  </span><span>Penelitian</span><span>ini</span><span>bertujuan</span><span>untuk</span><span>memprediksi</span></span><span lang="IN">aktivitas </span><span>sitotoksik</span><span lang="IN"> dan toksisitas </span><span>dari</span><span> <span class="hps"><span lang="IN">duapuluh </span></span></span><span class="hps"><span>tiga</span><span lang="IN"> senyawa </span><span>turunan</span></span><em><span lang="IN">N</span></em><span lang="IN">-(benzoil)-<em>N</em>’-feniltiourea </span><span class="hps"><span>sebagai</span><span>calon</span><span>obat</span><span>antikanker</span><span lang="IN">. </span><span lang="EN-GB">Salah satu</span><span lang="EN-GB">mekanisme</span><span lang="EN-GB">kerja</span><span lang="EN-GB">turunan</span></span><em><span lang="IN">N</span></em><span lang="IN">-(benzoil)-<em>N</em>’-feniltiourea </span><span>sebagai</span><span>antikanker</span><span> <span lang="IN">adalah </span></span><span>menghamba</span><span lang="IN">t </span><span lang="IN">VEGF</span><span>R2</span><span>,</span><span>regulator</span><span>penting</span><span>untuk proses angiogenesis, serta</span><span>sangat</span><span>berperan</span><span>untuk</span><span>pertumbuhan tumor dan metastasis.</span><span lang="IN"> Aktivitas biologis dapat diprediksi melalui pemodelan molekul yang disebut uji <em>in silico</em>, </span><span>menggunakan program </span><span class="hps"><span lang="EN-GB">MVD (<em>Molegro Virtual Dock</em></span><em><span lang="IN">er</span></em><span lang="EN-GB">),</span><span>s</span></span><span lang="IN">edang toksisitas </span><span>dapat</span><span lang="IN"> diprediksi menggunakan program </span><span>pkCSM</span><span>dan</span><span>Protox</span><em><span>online tool</span><span lang="IN">. </span></em><span>Uji </span><em><span lang="IN">in </span><span>silico</span></em><span> dilakukan dengan </span><span lang="IN">melakukan </span><em><span>docking</span></em><span> senyawa yang akan </span><span lang="IN">di</span><span>prediksi aktivitasnya dengan target reseptor, VEGFR2, PDB ID. 3WZE</span><span>.</span><span class="hps"><span>Hasil</span><em><span>do</span><span lang="IN">c</span><span>king</span></em><span>berupa</span><span>energi</span><span>ikatan</span></span><span>digambarkan</span><span>dengan</span><span>nilai</span><span> <em><span lang="IN">R</span></em></span><em><span>erank</span><span> <span lang="IN">S</span></span><span>core (RS).</span></em><span>S</span><span class="hps"><span lang="IN">enyawa dengan </span><span>nilai<em> RS</em></span><span lang="IN"> kecil berarti mempunyai ikatan ligan</span><span>-</span><span lang="IN">reseptor yang stabil dan diprediksi m</span><span>empunyai</span><span> <span lang="IN">aktivi</span></span><span>tas yang b</span><span lang="IN">esar<em>. </em></span><span>Dari hasil</span><span>uji</span><em><span>in silico</span></em><span>disimpulkan</span><span>bahwa</span><span>semua</span><span>turunan</span></span><em><span lang="IN">N</span></em><span lang="IN">-</span><span>(b</span><span lang="IN">enzoil</span><span>)</span><span lang="IN">-<em>N</em>’-feniltiourea </span><span>diprediksi</span><span>menimbulkan</span><span>toksisitas relatif</span><span>rendah, dan</span><span>mempunyai a</span><span lang="IN">ktivitas </span><span>s</span><span lang="IN">itotoksik</span><span> lebih</span><span>besar</span><span>dibanding</span><span>hidroksiurea, tetapi</span><span>masih</span><span>lebih</span><span>rendah</span><span>dibanding</span><span>sorafenib.</span><em><span>N</span></em><span>-(4-</span><span lang="IN">p</span><span>ropoksibenzoil)-<em>N</em>’-feniltiourea</span><span>dan</span><em><span>N</span></em><span>-(3,5-di-trifluorometilbenzoil)-<em>N</em>’-feniltiourea</span><span><a href="https://www.google.com/url?sa=t&amp;rct=j&amp;q=&amp;esrc=s&amp;source=web&amp;cd=1&amp;cad=rja&amp;uact=8&amp;ved=0ahUKEwjV3I6185jOAhWBtZQKHTaPDG0QFggeMAA&amp;url=http%3A%2F%2Fwww.sigmaaldrich.com%2Fcatalog%2Fproduct%2Faldrich%2F173452&amp;usg=AFQjCNFKqXN5rZl13Bp_czI1YlfKyGvWRQ"><span lang="IN">diprediksi mempunyai aktivitas </span><span>sitotoksik</span><span lang="IN"> paling besar</span></a></span><span> tetapi menimbulkan hepatotoksik, sehingga sebagai senyawa terpilih untuk disintesis dan dikembangkan lebih lanjut adalah <em>N</em>-(3,4-dimet</span><span lang="IN">i</span><span>lbenzo</span><span lang="IN">i</span><span>l)-<em>N</em>’-</span><span lang="IN">f</span><span>en</span><span lang="IN">i</span><span>ltiourea</span><span lang="IN">.</span>

BACKGROUND<br />Many tumors express on their receptor tyrosine kinases vascular endothelial<br />growth factor activity associated with angiogenesis. Inhibition of<br />angiogenesis through reduction of tyrosine kinase activity is a promising<br />strategy for cancer therapy. The present study aimed to determine the<br />mechanism and potency of ethyl p-methoxycinnamate (EPMC) isolated<br />from Kaempferia galanga as angiogenesis inhibitor.<br />METHODS<br />A laboratory experimental study was conducted using chorio-allantoic<br />membranes (CAMs) of nine-day old chicken eggs induced by 60ng basic<br />fibroblast growth factor (bFGF). Ethyl p-methoxycinnamate (EPMC) potency<br />was determined at dosages of 30, 60, 90 and 120 μg and compared with<br />celecoxib 60 μg as reference drug and one negative bFGF-induced control<br />group. Neovascularization and endothelial cell count in CAM blood vessels<br />were evaluated. To predict the antiangiogenic mechanism of EPMC, a<br />docking study was performed with the Molegro Virtual Docker program on<br />tyrosine kinase as receptor (PDB 1XKK).<br />RESULTS<br />Angiogenesis stimulation by bFGF was prevented significantly (p&lt;0.05)<br />by EPMC at dosages of 30, 60, 90 and 120 μg and this activity was dose<br />dependent. Molecular docking showed interaction between EPMC functional<br />groups and tyrosine kinase amino acids at Met766, Met793, Thr854, Thr790,<br />Gln791 and Ala743. There was an association between EPMC<br />antiangiogenic activity and docking study results.<br />CONCLUSIONS<br />Ethyl p-methoxycinnamate is a potential new angiogenesis inhibitor through<br />interaction with tyrosine kinase. EPMC could be a promising therapeutic<br />agent for treatment of angiogenesis-related diseases.

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Purpose: To synthesise derivatives of N-allylthiourea and evaluate their anticancer activities against epidermal growth factor receptor (EGFR) using in silico and in vitro methods. Methods: Four compounds were synthesized using the Schotten-Baumann reaction. The structures of the synthesized compounds were confirmed using infrared (IR), proton nuclear magnetic resonance (1 H-NMR), carbon nuclear magnetic resonence (13 C-NMR) and electrospray ionization mass spectrometry (ESI-MS) methods. Molecular modeling was carried out with Molegro Virtual Docker version 5.5 through docking of the compounds onto the protein binding site of EGFR, with protein data bank (PBD) codes 1M17, 1XKK, and 3POZ. In vitro cytotoxicity was evaluated in MCF-7 cell lines using MTT assay. Results: The synthesized compounds showed lower Rerank Scores, relative to N-allylthiourea and hydroxyurea. The low Rerank Score values implied stable molecular bonds, and hence higher biological activities. In addition, the derivatives showed cytotoxicities against MCF-7 cell line (IC50: 0.21-0.38 mM) which were superior to those of N-allylthiourea (IC50: 5.22 mM) and hydroxyurea (IC50: 2.89 mM). Conclusion: The predicted anticancer activities of the synthesized compounds are consistent with results from in silico studies and assays of cytotoxicity against MCF-7 cell lines. Thus, N-allylthiourea derivatives can potentially be developed as anticancer drugs.

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)

This study aimed to predict the physicochemical proper es, pharmacokine c proper es (ADME), toxicity, and analgesic ac vity of 30 compounds of N-benzoylthiourea deriva ves that are poten al analgesic drugs. One of the mechanisms of ac on of N-benzoylthiourea deriva ves is the inhibi on of the cyclooxygenase-2 (COX-2) isoenzyme. An in silico test was performed by docking a compound that would predict its ac vity with the target COX-2 isoenzyme, PDB ID: 1PXX, using the MVD (Molegro Virtual Docker) program. The result of the docking was a form of energy bond indicated by the value of the rerank score (RS), where compounds that had lower RS values were predicted to have a higher ac vity. The pkCSM and Protox online tools were used to predict various physicochemical proper es. Based on the RS values, the Nbenzoylthiourea deriva ves can be predicted to have lower analgesic ac vity than diclofenac, the reference ligand. Three of the N-benzoylthiourea deriva ves-N-(2,4-bis-trifluoromethyl)-benzoylthiourea, N- (3,, respec vely, sugges ng that these compounds were predicted to have analgesic ac vity rela vely similar to diclofenac (RS value = -95.16). Furthermore, the majority of the N-benzoylthiourea deriva ves were predicted to have good pharmacokine c proper es (ADME), and cause rela vely low toxicity.

Tubuh manusia akan mengalami penuaan dan menyebabkan kenaikan resiko penyakit dan pada akhirnya menyebabkan kematian. Fenomena tersebut dapat muncul salah satunya akibat penurunan homeostasis tubuh karena menurunnya hormon estrogen. Salah satu senyawa yang berpotensi mengatasi keadaan tersebut adalah fitoestrogen dari golongan flavonoid. Potensi senyawa flavonoid dengan aktivitas fitoestrogenik, dapat diketahui dengan melakukan pengamatan In silico terhadap Estrogen Receptor ? (ER-?) dengan molecular docking. Tujuan penelitian ini adalah untuk mengetahui mekanisme senyawa fitoestrogen melalui jalur ER-dependent lain seperti ER-?. Tahapan molecular docking dilakukan menggunakan plug-in Autodock Vina dalam PyRX 0.8. Hasilnya diketahui senyawa apigenin, quercetin, kaempferol, katekin, genistein dan daidzein memiliki interaksi agonis terhadap ER-?. Interaksi yang diperoleh dapat menggambarkan bahwa senyawa tersebut mampu memberikan aktivitas estrogenik ketika membentuk ikatan ligan reseptor.

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.