Activity Screening and Structure Modification of Trigonelline as New Anticancer Drug for Non Small Cell Lung Cancer Through In Silico

Abstract

The biggest case of death in 2018 is caused by lung cancer. Non-small cell lung cancer (NSCLC) is most common. One of the cause lung cancer is the over expression of EGFR. Erlotinib is the first line of anticancer for NSCLC with EGFR mutations. However, erlotinib can cause side effects such as liver damage therefore new safe anticancer is needed. Trigonelline is an alkaloid compound from coffee beans that had anticancer activity in pancreatic cancer cells by inhibiting Nrf2 in vitro and in vivo at concentrations of 0.1-1 µM. Development of cancer cells by Nrf2 is regulated by EGFR. In this study screening and modification of trigonelline structure was carried out to obtain compounds that have anticancer activity on NSCLC against EGFR computationally. The research procedures carried out are modification of ten trigonelline derived structures, the molecular docking and prediction of physicochemical profiles from trigonelline and its modification also their ADMET. Based on results, KF9 has the lowest free energy of binding which was -8,88 kcal/mol and binds to Met769 which has biological activity with receptor. KF9 has good physiochemical profile and absorption, distribution, also toxicity parameters. KF9 has potential to become a new anticancer drug for NSCLC.Keywords: Coffee, Drug discovery and Drug development, Molecular structure modification, Nonsmall cell lung cancer, Trigonelline

Activity Screening and Structure Modification of Artocarpin Against Ace2 and Main Protease Through in Silico Method

“…Absorption, distribution, and toxicity are very important in the pharmaceutical field to assess a drug candidate in the body [26]. Absorption parameters consist of HIA (Human Intestinal Absorption) and permeability to Caco-2 cells and distribution parameters, namely PPB (Protein Plasma Binding) and BBB (Blood Brain Barrier) and toxicity parameters consisting of carcinogenic and mutagenic properties (table 4).…”

Potential of Hanjeli (Coix lacryma-jobi) essential oil in preventing SARS-CoV-2 infection via blocking the Angiotensin Converting Enzyme 2 (ACE2) receptor

“…Construction of 2D, 3D Compound Structures and SMILES Code 2D and 3D compound structures were created using the ChemDraw application (Pratama et al 2020). The structure of the compound to be tested was previously drawn using the ChemDraw 2D version 19.0 application.…”

“…The following was a table of compound images that were tested in 3D: Based on Table 2, it was known that the test compounds belonged to the polydentate ligand group. Moreover, ligands were grouped according to the number of donor atoms, and polydentate ligands could donate more than two atoms (Pratama et al 2020). In the structure of the test compound, there were more than two donor atoms where the atom that acted as a donor was an oxygen atom (O).…”