Peyote Alkaloids to Treat Alcoholism: A virtual screening analysis for receptor affinity estimation.

FEDERICO ZAMBERLAN; CARLA PALLAVICINI; FEDERICO ISSOGLIO; LUCAS DEFELIPE; LAURA ALETHIA DE LA FUENTE; ENZO TAGLIAZUCCHI

Mar del Plata

Congreso; X Congreso Argentino de Bioinformática y Biología Computacional; 2018

Lophophora williamsii, known as ?peyote? in the occidental culture, it is a spineless cactus from the Chihuahuan Desert with hallucinogen properties, which can be explained by the presence of the psychedelic alkaloid mescaline as its main constituent. The amount of diverse alkaloids present in this particular species is remarkably large in comparison with other members of the family Cactaceae. Despite the evidence of promising therapeutic uses of these compounds, the individual pharmacology of only a few of these it is known. The Huichol indigenous people of northern Mexico who consume it in their religious ceremonies reports that this plant has different therapeutic qualities other than its visionary power, particularly, evidence suggests its possible capability to treat alcoholism. In this work we focus on the hypothesis that some of the peyote alkaloids could have a pharmacology similar to the antiemetic 5-HT3 antagonist ondansetron, as a possible explanation to this therapeutic characteristic. To discover which of L. williamsii constituents could explain this phenomenon, before synthesizing each molecule for in vivo tests, we designed a method which applies different computer chemistry techniques to find possible candidates for alcoholism treatment.In order to obtain the affinity profiles of these alkaloids for the different receptors in the brain, and thus predict their psychopharmacological effects, we proceeded to estimate such values through their structural similarity with known already assayed medications. Using open-source data mining software we extracted the molecular structures with their respective affinity values from two public access chemical databases and realized a virtual screening process for estimating the receptor profile of our group of drugs.