INTERACTIONS OF HYBRID PORPHYRIN-ACRIDINE COMPOUNDS WITH DUPLEX DNA AND CANCER RECEPTORIS : IN SILICO STUDY

• Main Author: Nashrullah Muhammad, Hubbi
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/78844
• Institution: Institut Teknologi Bandung

Cationic porphyrin compounds are porphyrin derivatives that have the potential to be used as anticancer agents because of their ability to accumulate in cancer cells and their strong interaction with DNA. Previous research have shown that organogold complexes show cytotoxic activites and are also potential anticancer agents. The aim of this study is to design cationic porphyrin compounds with meso-substituents pyridine, imidazole, and pyrazole, conjugated with acridine to form hybrid porphyrin-acridine (P-A) compounds, and also their gold complexes. The interactions of the P-A compounds with duplex DNA, peroxiredoxin, and vascular endothelial growth factor 2 (VEGFR-2) is studied using in silico methods. This study was performed in silico to obtain a model for P-A compounds and their gold complexes which interact well with duplex DNA, the enzyme peroxiredoxin, and VEGFR-2. Firstly, a density functional theory (DFT) study was perofonned to determine the electronic properties and global reactivity descyiptors of the P-A compounds. Next, analysis of the interactions of the P-A compounds with duplex DNA, peroxiredoxin, and VEGFR-2 was performe& using molecular docking techniques. Finally, further analysis on the interactions were carried out through molecular dynamics (MD) studies. The results of the DFT study showed that H2PAC, bis-H2PyP-AC, bis-H21mP-AC, and tris-H2PyP-AC have favourable reactivity parameters towards Au3+ The H2P-AC compound showed the highest affinity towards duplex DNA when binding at the minor groove, while bis-H2PyPAC showed the highest affinity when interacting through intercalation. The porphyrin-acridine compounds showed higher affinity towards peroxiredoxin compared to its natural ligand and the reference compounds, with H2P-AC having the lowest free binding energy. Meanwhile, all porphyrin-acridine compounds have higher affinites towards VEGFR-2 compared to peroxiredoxin. The results of the MD simulations indicate that all interactions of the P-A compounds to duplex DNA are stabl. We have performed an initial in silico design and development of hybrid porphyrin-acridine compounds that have high reactivity towards the metal ion Au3+ high affinites and stable interactions towards duplex DNA, peroxiredoxin, and VEGFR-2.