A comparative analysis of In vitro and In vivo efficacies of the enantiomers of thioridazine and its racemate

TY - JOUR

T1 - A comparative analysis of In vitro and In vivo efficacies of the enantiomers of thioridazine and its racemate

AU - Christensen, Jørn Bolstad

AU - Hendricks, Oliver

AU - Chaki, Shawasti

AU - Mukherjee, Sayanti

AU - Das, Ayan

AU - Pal, Tapan K.

AU - Dastidar, Sujata G.

AU - Kristiansen, Jette E.

PY - 2013/3/7

Y1 - 2013/3/7

N2 - A long list of chemotherapeutical drugs used in the treatment of the peripheral and the central nervous systems possess anti-microbial activity. Some of these neurotropic compounds are chiral, with the one stereo isomeric form exaggerating reduced neurotropism. This is the case for the levorotatory form of thioridazine. The phenothiazine thioridazine is an interesting compound, characterized by exhibiting a significant growth inhibiting activity on a wide array of micro-organisms. Thioridazine is characterized by another challenging feature, because the compound is concentrated in certain human tissue cells. The present study describes a comparative study of the two enantiomers as well as the racemic form of thioridazine. The study exploits the stereochemical aspect and the in vitro and in vivo potential of these compounds, with a focus on the effects on Gram negative organism Salmonella enterica serover Typhimurium. In summary, the results of this study yielded a significant antibacterial activity of all forms of thioridazine, indicating the levorotatory (-)- form to be superior in terms of both its in vitro and in vivo efficacies.

AB - A long list of chemotherapeutical drugs used in the treatment of the peripheral and the central nervous systems possess anti-microbial activity. Some of these neurotropic compounds are chiral, with the one stereo isomeric form exaggerating reduced neurotropism. This is the case for the levorotatory form of thioridazine. The phenothiazine thioridazine is an interesting compound, characterized by exhibiting a significant growth inhibiting activity on a wide array of micro-organisms. Thioridazine is characterized by another challenging feature, because the compound is concentrated in certain human tissue cells. The present study describes a comparative study of the two enantiomers as well as the racemic form of thioridazine. The study exploits the stereochemical aspect and the in vitro and in vivo potential of these compounds, with a focus on the effects on Gram negative organism Salmonella enterica serover Typhimurium. In summary, the results of this study yielded a significant antibacterial activity of all forms of thioridazine, indicating the levorotatory (-)- form to be superior in terms of both its in vitro and in vivo efficacies.

U2 - 10.1371/journal.pone.0057493

DO - 10.1371/journal.pone.0057493

M3 - Journal article

C2 - 23505431

SN - 1932-6203

VL - 8

JO - P L o S One

JF - P L o S One

IS - 3

M1 - e57493

ER -