Searching of protein targets for alpha lipoic acid

Abstract

Ácido alfa lipóico (ALA) é um dos oxidantes mais poderosos e um cofactor em complexos enzimáticos, apesar de seus mecanismos ainda não serem conhecidos. A pesquisa por alvos proteicos de ALA é fundamental para compreender seus processos de sinalização. Uma abordagem bioinformática foi usada a fim de se encontrar alvos hipotéticos para ALA usando o servidor Target Fishing Dock (TarFisDock). Contagens de afinidade para os melhores resultados foram calculadas pelo AutoDock Vina. Alvos relevantes incluíram leucotrieno A4 hidrolase, canal de potássio voltagem-dependente, alfa-hidroxiesteróide desidrogenase, epóxido hidrolase, proteínas estas envolvidas no câncer, diabetes, desordens neurológica e cardiovascular. As energias de interação corrigidas segundo padrão conterpoise foram calculadas para proteínas que ligam R-ALA, e mostraram interações R-ALA-resíduos favoráveis. A sobreposição de R-ALA com inibidores conhecidos daquelas proteínas, permitu concluir que R-ALA adota diferentes conformações espaciais em seus sítios de ligação, podendo ser um inibidor fraco plausível destes alvos e, portanto, este efeito deveria ser considerado quando da realização de estudos sobre seus efeitos bioquímicos.Alpha lipoic acid (ALA) is one of the most powerful antioxidants and a cofactor in enzyme complexes, although its mechanisms are still unknown. The search for protein targets of ALA is fundamental to understand its signaling pathways. A bioinformatics approach was used to find hypothetical targets for ALA using the Target Fishing Dock Server (TarFisDock). Affinity scores for the best hits were calculated by AutoDock Vina. Relevant targets included leukotriene A4 hydrolase, voltage gated potassium channel, alpha hydroxysteroid dehydrogenase and epoxide hydrolase, proteins involved in cancer, diabetes, and neurological and cardiovascular disorders. The counterpoise-corrected interaction energies calculated for proteins that bind R-ALA showed favorable interactions R-ALA-residues. Superpositioning of R-ALA with known inhibitors of those proteins, together with the finding that R-ALA adopts different spatial conformations in their binding sites, suggests R-ALA could be a plausible weak inhibitor of these targets, and this effect should be considered when studying its biochemical effects.

Therapeutic Potential of Alpha-Lipoic Acid in Viral Infections, including COVID-19

“…Maldonado-Rojas and colleagues (2011) performed an in silico screening of the molecular targets for LA, and, among several targets, leukotriene A4 hydrolase, voltage-gated potassium channel, alpha hydroxysteroid dehydrogenase, and epoxide hydrolase were found to be the most likely bound by LA. As these genes are involved in the pathogenesis of a number of diseases, this finding supports the potential use of LA in the treatment of cancer, diabetes, and neurological and cardiovascular disorders [ 36 ].…”

Possible Molecular Mechanisms and Pathways Involved in Bh3 Mimetic Activity of Alpha-Lipoic Acid on Human Colon Cancer Cell Line

“…It might be feasible to develop agents by "BH3 profiling" with individual prosurvival Bcl-2 family members like targets [52]. The search of protein targets of ALA as well as docking of the binding site is necessary to understand and support its physiological roles and pharmacological effects [2]. Considering the promising biological results in order to evaluate the mode of possible interaction of ALA and 5-FU with Bcl-2 and Bax targets, molecular docking of these compounds and some known Bcl-2 inhibitors and Bax activators was carried out and results were compared.…”

“…Alpha-lipoic acid (ALA), a small dithiol molecule derived from octanoic acid, may act as a powerful micronutrient with diverse pharmacological and antioxidant properties [1]. This naturally-occurring antioxidant, known as a vitamin, co-factor of some mitochondrial enzymes (pyruvate dehydrogenase, αketoglutarate dehydrogenase, glycine decarboxylase), potent free radical scavenger and drug candidate, may be de novo synthesized in small amounts by animals and humans [2,3]. It can also be absorbed from dietary sources such as red meat, potatoes and may be present in wheat and, to a lesser degree, in fruits and vegetables [4,5].…”

Governing the Inhibition of Reconstituted Collagen Type I Assemblies Mediated Through Noncovalent Forces of (±)-α Lipoic Acid

“…Another important role is that, it plays as an amphiphilic metal chelator in lead and mercury toxicity because it can potentially cross the blood–brain barrier and a rich antioxidant predominantly reacts with the reactive oxidative species or may even inactivate the free radicals. It contributes to other biological activities such as antimutagenic, anticarcinogenic, antiageing, and antidiabetic, and it prevents central nervous system disorders. , It is also a potent therapeutic agent which demonstrates an effective treatment against diabetic cardiomyopathy by altering signaling pathways, mitochondrial oxidative stress, cardiac dysfunction, and ECM remodeling in the diabetic rats . The impact on the oxidative damage caused by a dysregulation of glucose metabolism was reduced by an antioxidant-rich (±)-ALA molecule …”