Uji in silico Aktivitas Sitotoksik dan Toksisitas Senyawa Turunan N-(Benzoil)-N’- feniltiourea Sebagai Calon Obat Antikanker

Abstract

<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>