In silico approach: Biological prediction of nordentatin derivatives as anticancer agent inhibitors in the cAMP pathway

Muhammad Ikhlas Abdjan, Nanik Siti Aminah, Imam Siswanto, Tin Myo Thant, Alfinda Novi Kristanti, Yoshiaki Takaya

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

A combination of computational techniques has been carried out to predict the binding of nordentatin derivatives based on pyranocoumarin semi-synthesis with the target protein from the expression of the PDE4B gene. The inhibition of the cAMP pathway is the main target of anti-cancer drugs, which is responsible for uncontrolled cell division in cancer. Modeling was done using a combination of semi-empirical methods and the density functional theory (PM3-DFT/6-31G∗/B3LYP) to obtain the optimal structure of a small ligand that could be modeled. Studies on the interaction of the ligands and amino acid residues on protein targets were carried out using a combination of molecular docking and molecular dynamic simulation. Molecular docking based on functional grid scores showed a very good native ligand pose with an RMSD of 0.93 Å in determining the initial coordinates of the ligand-receptor interactions. Furthermore, the amino acid residues responsible for interaction through H-bonds were Tyr103, His104, His177, Met217, and Gln313. The binding free energy (kcal mol-1) results of the candidates were PS-1 (-36.84 ± 0.31), PS-2 (-35.34 ± 0.28), PS-3 (-26.65 ± 0.30), PS-5 (-42.66 ± 0.26), PS-7 (-35.33 ± 0.23), and PS-9 (-32.57 ± 0.20), which are smaller than that of the native ligand Z72 (-24.20 ± 0.19), and thus these have good potential as drugs that can inhibit the cAMP pathway. These results provide theoretical information for the efficient inhibition of the cAMP pathway in the future.

Original languageEnglish
Pages (from-to)42733-42743
Number of pages11
JournalRSC Advances
Volume10
Issue number70
DOIs
Publication statusPublished - 25 Nov 2020

Fingerprint

Dive into the research topics of 'In silico approach: Biological prediction of nordentatin derivatives as anticancer agent inhibitors in the cAMP pathway'. Together they form a unique fingerprint.

Cite this