No 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

More than 111 million people worldwide have been affected by the COVID-19 outbreak caused by SARS-CoV-2. The main therapeutic target of COVID-19 is main protease (Mpro). It plays a key role as an enzyme in the SARS-CoV-2 replication and transcription. In this case, the alpha-mangostin potentially has antiviral activity against Mpro by inhibiting this enzyme. Nevertheless, the alpha-mangostin has low solubility and a lack of information about alpha-mangostin activity against the SARS-CoV-2. The aim of this study is to describe the molecular interactions and identify the pharmacokinetics profile between alpha-mangostin and its derivatives. in silico study was conducted by pharmacokinetics and toxicity prediction, molecular docking simulation, and Lipinski's rule of five. FKS9 has a Gibbs free energy value of-10.5 kcal/mol with an inhibition constant of 36.45 μM and an interaction with amino acid His41 residue. Its human intestinal absorption and Caco-2 values were 95.13% and 47.71% while the plasma protein binding and blood-brain barrier values were 96.66% and 6.99%. FKS9 also has no mutagenic and carcinogenic potential. FKS9 as an alpha-mangostin derivative had the best interaction with the Mpro enzyme and its pharmacokinetic profiles was identified.