Interaction of heterocyclic thiols/thiones eliminated from cephalosporins with iodine and its biological implications.
Hydrolysis of beta-lactam antibiotics by beta-lactamases (e.g., metallo-beta-lactamase, mbetal) is one of the major bacterial defense systems. These enzymes can catalyze the hydrolysis of a variety of antibiotics including the latest generation of cephalosporins, cephamycins and imipenem. It is shown in this paper that the thiol/thione moieties eliminated from certain cephalosporins by mbetal-mediated hydrolysis readily react with molecular iodine to produce ionic compounds having S-I bonds. While the reaction of MTT with iodine produced the corresponding disulfide, MDT and DMETT produced the charge-transfer complexes MDT-I(2) and DMETT-I(2), respectively. Addition of two equivalents of I(2) to MDT produced a novel cationic complex having an almost linear S-I(+)-S moiety and I(5)(-) counter anion. However, this reaction appears to be highly solvent dependent. When the reaction of MDT with I(2) was carried out in water, the reaction produced a monocation having I(5)(-), indicating the reactivity of MDT toward I(2) is very similar to that of the most commonly used antithyroid drug methimazole (MMI). In contrast to MMI, MDT and DMETT, the triazine-based compound MTDT acts as a weak donor toward iodine.
Tamilselvi
A
A
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, India.
Mugesh
Govindasamy
G
D013956:Antithyroid Agents / Q000737:chemistry; D002511:Cephalosporins / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry; D006868:Hydrolysis; D007455:Iodine / Q000737:chemistry* / Q000145:classification*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013871:Thiones / Q000737:chemistry*
D013956:Antithyroid Agents; D002511:Cephalosporins; D006571:Heterocyclic Compounds; D013438:Sulfhydryl Compounds; D013871:Thiones; D007455:Iodine