Dự đoán hoạt tính kháng hemozoin của các chất từ thư viện VICB và MMV Malaria Box bằng phương pháp in silico

Abstract

With regard that in development of new mechanisms or novel anti-malarial compounds to control antimalarial drug resistance and eliminate malaria, hemozoin formed by hemoglobin degradation of Plasmodium falciparum as the unique heme detoxification pathway, is known as a novel potential target for antimalarial drug discovery,... this study was aimed to predict anti-hemozoin activity from the VICB library and the MMV Malaria Box using in silico approach. A total 75 compounds from VICB library and the MMV Malaria Box as hemozoin inhibitors were collected for building a 2D-QSAR model using partial least square algorithm in MOE package. This 2D-QSAR model was successful built with the predictive parameters R² = 0.79, and RMSE - 0.1. Subsequently the model was applied to predict anti-hemozoin activity for 18560 compounds from Traditional Chinese medicine database after selecting through Lipinski 5 rules. As predictive results, 3233 compounds showed having the IC₅₀ ≤ 10 µM, and the terpenoid compounds potential antimalarial agents. These results might be useful for designing new hemozoin inhibitors in development of new antimalarial drugs.