On March 31, 2020, Silva, Daniel; Mendes, Eduarda; Summers, Eleanor J.; Neca, Ana; Jacinto, Ana C.; Reis, Telma; Agostinho, Paula; Bolea, Irene; Jimeno, M. Luisa; Mateus, M. Luisa; Oliveira-Campos, Ana M. F.; Unzeta, Mercedes; Marco-Contelles, Jose; Majekova, Magdalena; Ramsay, Rona R.; Carreiras, M. Carmo published an article.Formula: C10H11N3O3S The title of the article was Synthesis, biological evaluation, and molecular modeling of nitrile-containing compounds: Exploring multiple activities as anti-Alzheimer agents. And the article contained the following:
Based on the monoamine oxidase (MAO) inhibition properties of aminoheterocycles with a carbonitrile group we have carried out a systematic exploration to discover new classes of carbonitriles endowed with dual MAO and AChE inhibitory activities, and Aβ anti-aggregating properties. Eighty-three nitrile-containing compounds, 13 of which are new, were synthesized and evaluated. In vitro screening revealed that 31, a new compound, presented the best lead for trifunctional inhibition against MAO A (0.34μM), MAO B (0.26μM), and AChE (52μM), while 32 exhibited a lead for selective MAO A (0.12μM) inhibition coupled to AChE (48μM) inhibition. Computational anal. revealed that the malononitrile group can find an advantageous position with the aromatic cleft and FAD of MAO A or MAO B. However, the total binding energy can be handicapped by an internal penalty caused by twisting of the ligand mol. and subsequent disruption of the conjugation (32 in MAO B compared to the conjugated 31). Conjugation is also important for AChE as well as the hydrophilic character of malononitrile that allows this group to be in close contact with the aqueous environment as seen for 83. Although the effect of 31 and 32 against Aβ1-42, was very weak, the effect of 63 and 65, and of the new compound 75, indicated that these compounds were able to disaggregate Aβ1-42 fibrils. The most effective was 63, a (phenylhydrazinylidene)propanedinitrile derivative that also inhibited MAO A (1.65μM), making it a potential lead for Alzheimer’s disease application. The experimental process involved the reaction of 2-Aminomalononitrile 4-methylbenzenesulfonate(cas: 5098-14-6).Formula: C10H11N3O3S
The Article related to nitrile compound acetylcholinesterase monoamine oxidase alzheimer agent biol evaluation, ache inhibitors, alzheimer’s disease, aβ1-42 disaggregating agents, mao inhibitors, in silico study, nitrile-containing compounds and other aspects.Formula: C10H11N3O3S
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts