Theoretical design of novel antimalarial agents against P. falciparum strain, Dd2 through the QSAR modeling of synthesized 2′-substituted triclosan derivatives

• Main Authors: Zakari Ya'u Ibrahim, Adamu Uzairu, Gideon Shallangwa, Stephen Abechi
• Format: Article
• Language: English
• Published: Elsevier 2020-09-01
• Series: Heliyon
• Subjects: Analytical chemistry; Theoretical chemistry; Pharmaceutical chemistry; QSAR; Molecular design; Antimalarial
• Online Access: http://www.sciencedirect.com/science/article/pii/S2405844020318752
• ISSN: 2405-8440

In an attempt to design compounds with higher antimalarial activities, quantitative structure-activity relationship (QSAR) technique was utilized in the development of a molecular model for some synthesized 2′-substituted triclosan derivatives through a hybrid of the GA-MLR method. The model was found to have excellent statistical parameters (R2 = 0.8919, R2Adj = 0.8728, LOF = 0.2563). The descriptors mean effect (MF) revealed BCUTw-1l, which increases with an increase in molecular weight, to be the most contributive to the antimalarial activity. Consequently, compound 3, with the highest activities (pEC50 = 6.9586) was deployed as the design template. The molecular weight of the template was increasing through substitutions of its atoms at several positions with heavier atoms/groups to increases the descriptor (BCUTw-1l) value. Twelves (12) theoretical derivatives of the template were designed where six of the designed derivatives have better activity than the design template. The most active designed compound, 3L was found to have the highest antimalarial activity (pEC50 = 7.930) than that of the design template.