Antivitamins for Medicinal Applications

Abstract

Antivitamins represent a broad class of compounds that counteract the essential effects of vitamins. The symptoms triggered by such antinutritional factors resemble those of vitamin deficiencies, but can be successfully reversed by treating patients with the intact vitamin. Despite being undesirable for healthy organisms, the toxicities of these compounds present considerable interest for biological and medicinal purposes. Indeed, antivitamins played fundamental roles in the development of pioneering antibiotic and antiproliferative drugs, such as prontosil and aminopterin. Their development and optimisation were made possible by the study, throughout the 20th century, of the vitamins' and antivitamins' functions in metabolic processes. However, even with this thorough knowledge, commercialised antivitamin-based drugs are still nowadays limited to antagonists of vitamins B9 and K. The antivitamin field thus still needs to be explored more intensely, in view of the outstanding therapeutic success exhibited by several antivitamin-based medicines. Here we summarise historical achievements and discuss critically recent developments, opportunities and potential limitations of the antivitamin approach, with a special focus on antivitamins K, B9 and B12 .

Recent trends in the development of vitamin B12derivatives for medicinal applications

“…15,47,48 This trend is probably inspired by the metabolic importance of Cbls and its unique properties, functions and reactivity in biological systems. 15,47,48 This trend is probably inspired by the metabolic importance of Cbls and its unique properties, functions and reactivity in biological systems.…”

“…This strong demand for B 12 makes antivitamins B 12 highly attractive for the design of therapeutic drugs 15,50. by inhibiting vitamin dependent enzymes 47,. by inhibiting vitamin dependent enzymes 47,.…”

Die Hydrogenobyrsäure‐Struktur enthüllt den Corrin‐Liganden als entatisches Zustandsmodul zur Steigerung der Katalyseaktivität von B12‐Cofaktoren

“…[6,11b,c,9,30] So diente Hby in unseren Laboren schon als Ausgangsmaterial fürd ie Synthese von B 12 -Übergangsmetall-Analoga, worüber in Kürze berichtet wird. [31] Die Aussicht auf spannende Untersuchungen von Übergangsmetallkomplexen der verdrillten Corrine wird fürI nteresse von experimentellen Wissenschaftlern und theoretischen Chemikern sorgen. [31] Die Aussicht auf spannende Untersuchungen von Übergangsmetallkomplexen der verdrillten Corrine wird fürI nteresse von experimentellen Wissenschaftlern und theoretischen Chemikern sorgen.…”

Antivitamin B12 Inhibition of the Human B12‐Processing Enzyme CblC: Crystal Structure of an Inactive Ternary Complex with Glutathione as the Cosubstrate

“…Application of antivitamins B 12 [5, 8] is a rather humane means in such studies [6, 9] Indeed, the antivitamin B 12 4-ethylphenylcobalamin ( 1 , EtPhCbl) induced functional B 12 deficiency in mice. [6, 10] Unfortunately 1 is susceptible to light-induced cleavage of its (Co-C)-bond, ‘uncaging’ its locked-in B 12 activity.…”