Potensi Senyawa Hidrazon berbasis Turunan 2-Tiohidantoin dan Hidrazida sebagai Inhibitor Protein E6 pada Kanker Serviks secara In Silico

Abstract

Every year, the prevalence of cervical cancer in the world is increasing. Cervical cancer can occur as a result of Human Papillomavirus (HPV) infection. Currently, E6 oncoprotein inhibition targeting tends to be chosen because it is safer and better as a therapeutic agent of cervical cancer. In addition, E6 is also a crucial virus that induces cervical cancer through the inactivation of the p53 protein so that effective materials are needed to inhibit the performance of E6 oncogenes. Hydrazone is a Schiff base compound that has an azomethine group (-NHN=CR-). It is this azomethine group that plays a role in various bioactivity, including antivirals and anticancer. In this study, hydrazone was derived from the derivatives of 2-thihidantoin and hydrazide. The compound 2-thihidantoin belongs to the heterocyclic group that plays an important role in drug chemistry such as anticonvulsant, antibacterial, antidiabetic, antiviral and anticancer. Thus, this compound can be an alternative agent for cervical cancer treatment. Before the synthesis of such materials, it is necessary to carry out bioactivity analysis using computing. The study of the in-silico method includes the creation of structures using Avogadro, optimization of molecular geometry using Gaussian 16, as well as the results of ligand-protein interactions (RMSD, KI, Binding Affinity, ADME, Binding Pocket, and Drugability score) using AutoDock 4.2, PyMol, LigPlot, SwissADME, PLIP Tools, and Protein Plus. The results showed that hydrazone compounds derived from 2-thiohidantoin and hydrazide derivatives have the potential to inhibit the E6 protein and can be used as oral drugs..