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    DFT Study on Mechanism and Kinetic of Thiotepa and Tepa Interaction with its DNA Receptor

    , M.Sc. Thesis Sharif University of Technology Torabifard, Hedieh (Author) ; Fattahi, Alireza (Supervisor)
    Abstract
    N, N′, N″-triethylenethiophosphoramide (Thiotepa) and its oxo analogue (Tepa) as the major metabolite are trifunctional alkylating agents with a broad spectrum of antitumor activity. In vivo and vitro studies show alkylation of DNA by Thiotepa and Tepa can follow two pathways, but it remains unclear which pathway represents the precise mechanism of action. In pathway 1, these agents are capable of forming cross-links with DNA molecules which can be carried out via two different mechanisms. In the first mechanism, the ring opening reaction is initiated by protonating the aziridine, which then becomes the primary target of nucleophilic attack by the N7-Guanine of DNA. The second one is the...