The quantitative structure-property relationships study of 40 benzoxazines, that seem to be very promising anti mycobacterial drugs, allowed proposing and testing of the equations describing effects of substituents on half-wave potentials of these compounds. Although two structural types of benzoxazines were studied (i.e. thioxobenzoxazinones and benzoxazinedithiones), it is possible to describe the effect of substituent on half-wave potentials of benzoxazines by one general equation. A good correlation for relationship between half-wave potential and energy of HOMO orbital was also found. The study of electrochemical oxidation of these compounds as a model of their possible metabolic degradation was performed. It was possible to propose general scheme of electrochemical oxidation of sulfur containing benzoxazine derivatives. From the metabolic point of view, desulfuration is the corresponding process to this pathway. As these derivatives were not examined in vivo, obtained results represent very beneficial clues, and, moreover, proposed scheme could serve as a support for the explanation of strong antimycobacterial activity of sulfur containing benzoxazines. (C) 2004 Elsevier Ltd. All rights reserved.