Electrochemical reduction mechanism of camptothecin at glassy carbon electrode.
Camptothecin (CPT) is a cytotoxic quinoline alkaloid endowed with the inhibition of topoisomerase I, an essential enzyme for the normal functioning of DNA. The redox behaviour of CPT was investigated at a glassy carbon electrode using cyclic, differential pulse and square wave voltammetry. It was shown that CPT can undergo reduction in a pH-dependent mechanism. In acid media only one irreversible charge transfer reaction was observed whereas by increasing the pH of the supporting electrolyte, two reduction peaks occurred. The diffusion coefficient of CPT was calculated in pH 4.5 0.1M acetate buffer using cyclic voltammetry to be D(CPT)=5.77x10(-6)cm(2)s(-1). Differential pulse voltammetry measurements were carried out over a wide pH range and allowed the determination of the number of electrons and protons transferred during each step in the CPT reduction mechanism, one electron and one proton. The use of square wave voltammetry proved the quasi-reversibility of CPT reduction as a function of the pH of the supporting electrolyte. Based upon the results obtained a reduction mechanism was proposed and the observed waves were attributed to the hydroxylation of the lactone ring of CPT to a lactol ring.
Shah
Afzal
A
Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3004-535 Coimbra, Portugal.
Diculescu
Victor C
VC
Qureshi
Rumana
R
Oliveira-Brett
Ana Maria
AM
D002166:Camptothecin / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D004563:Electrochemistry; D004566:Electrodes; D005898:Glass / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D007783:Lactones / Q000737:chemistry; D010084:Oxidation-Reduction; D059004:Topoisomerase I Inhibitors / Q000737:chemistry*
D007783:Lactones; D059004:Topoisomerase I Inhibitors; D002244:Carbon; D002166:Camptothecin