23rd Congress of the International Union for Biochemistry and Molecular Biology
44th Annual Meeting of the Brazilian Society for Biochemistry and Molecular Biology
th
th
Foz do Iguaçu, PR, Brazil, August 24 to 28 , 2015
BINDING ANTICANCER DRUGS TO THE HUMAN SERUM ALBUMIN PROTEIN:
DOCKING AND QUANTUM BIOCHEMISTRY DESCRIPTIONS TO
UNDERSTAND/SUGGEST THEIR PHARMACOKINETICS.
Nascimento, T.F1; Barroso-Neto, I.L.2; Lima-Neto, P.2; Pessoa, C.O.;3 Sousa, B.L.,1
Simões, R.C.;4 Freire, V.N.;1
1
Universidade Federal do Ceará, Departamento de Física, Fortaleza, Brasil;
2
Universidade Federal do Ceará, Departamento de Química, Fortaleza, Brasil;
Universidade Federal do Ceará, Departamento de Fisiologia e Farmacologia,
Fortaleza, Brasil; 4Universidade Federal do Oeste da Bahia, Centro das Ciências
Biológicas e da Saúde, Barreiras, Brasil
3
Current strategies in drug design are focusing also on the development of some degree
of control of the pharmacokinetics of medicines as, for example, by looking for drug
derivatives with binding characteristics that affect their transport by proteins like
albumin. Nowadays computer scientists can use methods of molecular and quantum
mechanics to provide expertise in the pharmacokinetics and biochemistry field of many
modes of drug action. The aim of this work is to elucidate the binding of important
anticancer drugs to human serum albumin (HSA), using classical and quantum
mechanical methods to provide relevant information of their albumin-related
pharmacokinetics. The binding of tambjamine J1, tambjamine I, Lapachol and Imatinib
to the HSA structure in the subdomains IA, IB, IIA, IIB, IIIA and IIIB were first evaluated
through docking procedures. After that, an improved evaluation was carried out through
a quantum biochemistry method within a divide to conquer methodology. For the
anticancer drugs studied, the site IB (IIIB) was find to be the most (less) relevant one
since the binding energy of all drugs were higher (smaller) than in the others HSA
binding sites. Finally, the quantum biochemistry computations unveils that the HSA
residues Tyr138 and Tyr161 are the most important contributing to the anticancer drugs
binding interaction with HSA.
Brazilian Society for Biochemistry and