IN SILICO INVESTIGATION OF XANTHONE DERIVATIVE POTENCY IN INHIBITING CARBONIC ANHYDRASE II (CA II) USING MOLECULAR DOCKING AND MOLECULAR DYNAMICS (MD) SIMULATION

REGINA KATELIA; MUHAMMAD MIFTAH JAUHAR; PUTRI HAWA SYAIFIE; DWI WAHYU NUGROHO; DONNY RAMADHAN; ADZANI GAISANI ARDA; ETIK MARDLIYATI; ISA ANSHORI

doi:10.22159/ijap.2022v14i5.45388

Authors

REGINA KATELIA Biomedical Engineering Department, School of Electrical Engineering and Informatics, Bandung Institute of Technology, Bandung, Indonesia https://orcid.org/0000-0002-8258-9167
MUHAMMAD MIFTAH JAUHAR Nano Center Indonesia, Jl. PUSPIPTEK, South Tangerang, Banten, 15314, Indonesia https://orcid.org/0000-0002-5826-5904
PUTRI HAWA SYAIFIE Nano Center Indonesia, Jl. PUSPIPTEK, South Tangerang, Banten, 15314, Indonesia https://orcid.org/0000-0001-8566-7960
DWI WAHYU NUGROHO Nano Center Indonesia, Jl. PUSPIPTEK, South Tangerang, Banten, 15314, Indonesia https://orcid.org/0000-0002-7020-8582
DONNY RAMADHAN Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency (BRIN), Cibinong, Bogor, Jawa Barat, 16911, Indonesia https://orcid.org/0000-0001-6556-3160
ADZANI GAISANI ARDA Nano Center Indonesia, Jl. PUSPIPTEK, South Tangerang, Banten, 15314, Indonesia https://orcid.org/0000-0002-2674-6295
ETIK MARDLIYATI Research Center for Vaccine and Drug, National Research and Innovation Agency (BRIN), Cibinong, Bogor, Jawa Barat, 16911, Indonesia
ISA ANSHORI Biomedical Engineering Department, School of Electrical Engineering and Informatics, Bandung Institute of Technology, Bandung, Indonesia

DOI:

https://doi.org/10.22159/ijap.2022v14i5.45388

Keywords:

Carbonic anhydrase (CA) II, Hypertension, Xanthone, Molecular docking, Molecular dynamics

Abstract

Objective: Hypertension is the leading contributor to all-cause death and disability worldwide. One of the most well-known first-line antihypertensive drugs is chlorthalidone which treats hypertension through carbonic anhydrase (CA) II inhibition. However, due to the high number of cases of hypertension, a more potent medication is still needed. Xanthone is a potential candidate for the compound group for its potency in inhibiting CA II. Therefore, this research aims to evaluate around 500 xanthones’ potency as a better oral antihypertensive drug than chlorthalidone.

Methods: 507 xanthones were analyzed for their potency using in silico method. Xanthone’s structures were retrieved from the PubChem website or built using Avogadro software, while the CA II receptor was retrieved from The RCSB website. Then molecular docking, ADME evaluation, and toxicity test were evaluated from selected ligands. Finally, a molecular dynamics simulation was conducted to evaluate the stability of the potential ligand as the inhibitor of CA II protein.

Results: This research found that globulixanthone c is considered to be a better CA II inhibitor compared to chlorthalidone. It is due to its lower binding affinity compared to chlorthalidone and its stable binding to CA II’s important inhibition sites with low fluctuation. It also has the potential to be consumed orally because it fulfills all of Lipinski's rule of five standards and its toxicity is on the moderate level.

Conclusion: Globulixanthone c, a type of prenylated xanthones group, showed the best potential activity as the inhibitor of CA II protein to treat hypertension among other xanthones.

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