Reactivity of 5a,6-anhydrotetracycline platinum(II) complex with biological nucleophiles: a theoretical study

Journal of the Brazilian Chemical Society

Costa, Luiz Antônio S.¹  Universidade Federal de Minas, Belo Horizonte, Brazil¹  Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil¹  Dos Santos, Hélio F.¹  Comando da Aeronáutica, Barbacena, Brazil¹  De Almeida, Wagner B.¹  Marcial, Bruna L.¹ 

关键词: cisplatin analogues;    tetracyclines;    ab initio calculations;   

DOI  :  10.1590/S0103-50532008000800002

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

This paper describes a theoretical analysis of the interaction between 5a,6-anhydrotetracycline platinum(II) complex (AHTC-Pt) and some biological nucleophiles; adenine (A), guanine (G), cysteine (Cys) and methionine (Met). The aquated species [Pt(AHTC)Cl(H2O)]+ was taken as reagent for the processes studied here. For DNA bases (A and G), the calculated values for ΔGa,aq at the B3LYP/6-311+G(2d,p) level were 21.7 and 20.7 kcal mol-1 for interaction with A and G, respectively, which are in accordance with the expected behavior of faster process involving G. These values are higher than the experimental activation energy for the parent compound cisplatin (18.5 kcal mol-1 for interaction with G). For the process involving the amino-acids, the barriers were 17.6 (Cys) and 18.5 kcal mol-1 (Met), which are lower than the observed values for cisplatin (20.5 and 20.2 kcal mol-1, respectively). These outcomes show that AHTC-Pt hybrid complex may be considered a promising lead compound in the development of novel anticancer drugs based on platinum complex.

【 授权许可】

Unknown