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QT-037
Combined Partial Least Squares and Quantum Chemical Study of Antimalarial Activity of
Artemisinins
Márcia M. C. Ferreira (PQ)*^a, Rudolf Kiralj (PQ)^a, José C. Pinheiro (PQ)^b, Oscar A. S. Romero (PQ)^b. marcia@iqm.unicamp.b
^aInstituto de Química, Universidade Estadual de Campinas, Campinas 13083-970, SP, Brasil. ^bDepartamento de Química, Universidade Federal do Pará, Belém 66075-110, PA, Brasil.

Key Words: multidrug resistance efflux, AcrB bacterial pump, chemometrics
Artemisinin and its derivatives are potential antimalarial agents even against Plasmodium falciparum, the most dangerous parasite. Artemisinin activity depends upon its activation by heme. Hence, its molecular features related to the interaction with heme are important for its activity. This work deals with 19 antimalarial artemisinins as 14/5 in the training/external validation set, and 10 proposed artemisinins as prediction set. Five molecular descriptors encoding steric and electronic properties were selected in the PLS modeling (three Principal Components, Q² = 0.83 and R² = 0.92, SEP = 0.375) and disciminated well low, moderately and high active molecules. New potential drugs have been proposed. LUMO+1 orbital lobes also discriminated well studied molecules in accord with their biological activities.
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XXVI Congresso Latinoamericano de Química/27^a Reunião Anual da Sociedade Brasileira de Química - SBQ