Brenig Christopher, Mestizo Paula Daniela, Zelder Felix
Department of Chemistry, University of Zurich Winterthurerstrasse 190 CH 8057 Zurich Switzerland
RSC Adv. 2022 Oct 7;12(44):28553-28559. doi: 10.1039/d2ra05748d. eCollection 2022 Oct 4.
This study describes the syntheses of four singly- and two doubly-modified vitamin B derivatives for generating antimetabolites of (). The two most potent antagonists, a Co-phenyl-cobalamin-,8-lactam and a 10-bromo-Co-phenylcobalamin combine a -lactam or 10-bromo modification at the "eastern" site of the corrin ring with an artificial organometallic phenyl group instead of a cyano ligand at the β-site of the cobalt center. These two doubly-modified B antagonists (10 nM) inhibit fully B-dependent (0.1 nM) growth of . In contrast to potent 10-bromo-Co-phenylcobalamin, single modified 10-bromo-Co-cyanocobalamin lacking the artificial organometallic phenyl ligand does not show any inhibitory effect. These results suggest, that the organometallic β-phenyl ligand at the Co center ultimately steers the metabolic effect of the 10-bromo-analogue.
本研究描述了四种单修饰和两种双修饰维生素B衍生物的合成，用于生成（）的抗代谢物。两种最有效的拮抗剂，一种钴-苯基-钴胺素-β-内酰胺和一种10-溴-钴-苯基钴胺素，在咕啉环的“东部”位点结合了β-内酰胺或10-溴修饰，在钴中心的β位点用人工有机金属苯基取代了氰基配体。这两种双修饰的B拮抗剂（10 nM）完全抑制了B依赖性（0.1 nM）的（）生长。与有效的10-溴-钴-苯基钴胺素相反，缺乏人工有机金属苯基配体的单修饰10-溴-钴-氰钴胺素没有显示出任何抑制作用。这些结果表明，钴中心的有机金属β-苯基配体最终决定了10-溴类似物的代谢效应。
