Resistance to Trimethoprim

摘要: Trimethoprim (2,4-diamino-5-(3′,4′5′-trimethoxybenzyl)pyrimidine) is one of a series compounds first fully described by Roth et al. (1962). These possess both antimalarial and antibacterial activity, the former activity exemplified pyrimethamine latter trimethoprim (Tp). Tp potent inhibitor dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase EC 1.5.1.3; DHFR), an enzyme that catalyzes NADPH-dependent reduction to tetrahydrofolate, cofactor required for metabolism some amino acids, purines thymidine. The structure its clinically used structural analogs, tetroxoprim, shown in Fig. 1. has several thousand-fold higher affinity bacterial DHFR than mammalian DHFR; synthesis tetrahydrofolate preferentially diminished as consequence this selective binding (Burchall 1973; Hitchings 1973).