9^{th European Chemistry Congress}

Biography

Biography: Neda Fayyazi

Abstract

Exploring potent compounds is a critical first step in the multi-target drug discovery. The primary mechanism of heme detoxification in malaria parasites is hematin crystallization and the target of the antimalaria compounds. A series of chloroquine analogues were designed using the repositioning approach to develop new anticancer compounds. The fingerprints of the protein ligand interaction and ADMET descriptors are used to build and asses’ model for structure based drug discovery to develop new scaffold based on chloroquine hybrid β-hematin inhibitors. In the present study, 50 novel potent chloroquine hybrid β-hematin inhibitors with their IC₅₀ values were collected, was applied. The model built by partial least square algorithm showed excellent predictive power with the correlation coefficients for calibration and cross validation of r² = 0.93 and q² = 0.72. We developed and validated QSAR model in prediction of a newly synthesized series of 4-aminoquinolin hybrids and evaluated for their biological activity as an external test series. These compounds were evaluated for cytotoxic cell lines and β-hematin inhibition. The target compounds exhibited high β-hematin inhibition activity and were 3-9 times more active than the positive control. Furthermore, all compounds exhibited moderate to high cytotoxic activity. Pharmacophore features from 10 derivatives in model were generated with HIP-HOP algorithm then used for structure based virtual screening in commercial databases; leading to the identification of the compound with the best score from ChEMBL was 2016904, previously reported as VEGFR-2 inhibitor. The 11 compounds selected have performed a multi-parameter analysis for the comparison of compounds regarding their correlation between dual potency, target evaluation and predicted ADMET properties for drug development.