In Silico Study of Eugenol, Cinnamaldehyde, Ethyl Para Methoxycinnamate, Curcumin, and Hesperidin as Antibacterials Against Levofloxacine-Resistant Indonesian H. pylori Strains

The occurrence of antibacterial resistance has become a global concern. The results of previous studies revealed many cases of antibacterial resistance of levofloxacin in H. pylori strains originating from Indonesia. Conventional attempts to obtain new antibacterial agents usually take a long time, other efforts are needed to speed up discovery. Databases that provide the structure of DNA gyrases cannot fully provide what is needed. This study aims to obtain the three-dimensional structure of DNA gyrase of the Indonesian H. pylori strain so that it can be used to simulate the interaction process of compounds that have the potential to be anti-H. pylori through in silico studies. This study used in silico methods to predict the absorption, distribution, metabolism, excretion, and toxicology of potential compounds. The next process involves screening for drug similarity based on criteria set by Muegge, Egan, Veber, Lipinski, and Ghose. The three-dimensional structure of DNA gyrase is formed from several samples of amino acid sequences from the Indonesian gyrA and gyrB H. pylori strains. Eligible potential compounds were subjected to molecular docking studies on gyrA and gyrB to obtain the best score. The three-dimensional structure of the Indonesian gyrA and gyrB H. pylori strains has been obtained. Eugenol, cinnamaldehyde, and ethyl p-methoxycinnamate were more easily absorbed compared to curcumin and levofloxacin as controls. Curcumin and hesperidin show poor absorption and longer distribution in the gastric mucosa, thus allowing long-term interaction with H. pylori. All compounds do not inhibit cytochrome P450, can be excreted by the body, and are non-toxic. The prediction of drug similarity passes only through curcumin and ethyl p-methoxycinnamate. The results of molecular docking concluded that curcumin and hesperidin had better scores than levofloxacin. Curcumin has the most potential as an anti-H. pylori.