New insights into the mechanistic action of methyldehydrodieugenol B towards Leishmania (L.) infantum via a multiplatform based untargeted metabolomics approach

Canuto, Gisele André Baptista; Dörr, Fabiane; Lago, João Henrique G.; Tempone, André G.; Pinto, Ernani; Pimenta, Daniel C.; Farah, João Pedro Simon; Alves, Maria Júlia M.; Tavares, Marina Franco Maggi

doi:10.1007/s11306-017-1193-z

Cited by 8 publications

(2 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Separations were performed in a DB5-MS column (60 m length, 0.32 mm internal diameter, 0.25 μm film 95% dimethylpolysiloxane/5% diphenyl polysiloxane, Agilent Technologies). The approach applied herein was adapted from a previously described method [ 45 ]. Briefly, He was used as carrier gas at a flow rate of 1.0 mL min −1 .…”

Section: Methodsmentioning

confidence: 99%

Untargeted Metabolomics Insights into Newborns with Congenital Zika Infection

et al. 2021

View full text Add to dashboard Cite

Zika virus (ZIKV), an emerging virus belonging to the Flaviviridae family, causes severe neurological clinical complications and has been associated with Guillain-Barré syndrome, fetal abnormalities known collectively as congenital Zika syndrome, and microcephaly. Studies have shown that ZIKV infection can alter cellular metabolism, directly affecting neural development. Brain growth requires controlled cellular metabolism, which is essential for cell proliferation and maturation. However, little is known regarding the metabolic profile of ZIKV-infected newborns and possible associations related to microcephaly. Furthering the understanding surrounding underlying mechanisms is essential to developing personalized treatments for affected individuals. Thus, metabolomics, the study of the metabolites produced by or modified in an organism, constitutes a valuable approach in the study of complex diseases. Here, 26 serum samples from ZIKV-positive newborns with or without microcephaly, as well as controls, were analyzed using an untargeted metabolomics approach involving gas chromatography–mass spectrometry (GC-MS). Significant alterations in essential and non-essential amino acids, as well as carbohydrates (including aldohexoses, such as glucose or mannose) and their derivatives (urea and pyruvic acid), were observed in the metabolic profiles analyzed. Our results provide insight into relevant metabolic processes in patients with ZIKV and microcephaly.

show abstract

Section: Methodsmentioning

confidence: 99%

Untargeted Metabolomics Insights into Newborns with Congenital Zika Infection

et al. 2021

View full text Add to dashboard Cite

show abstract

“…[2] The method has mainly been used for determination of the mode of action of antimicrobial agents, which in many cases have proven very successful–especially for enzymatic targets. [3–10] The use of cell-lines to probe the mode of action of experimental drugs is less common, although there are successful examples. [11–18] Untargeted metabolomics screens are rather cost- and labor-effective and can give important and complementary information to other methods in the elucidation of a compounds biological mode of action.…”

Section: Introductionmentioning

confidence: 99%

Metabolic effects of an aspartate aminotransferase-inhibitor on two T-cell lines

Antti

Sellstedt

2018

PLoS ONE

View full text Add to dashboard Cite

An emerging method to help elucidate the mode of action of experimental drugs is to use untargeted metabolomics of cell-systems. The interpretations of such screens are however complex and more examples with inhibitors of known targets are needed. Here two T-cell lines were treated with an inhibitor of aspartate aminotransferase and analyzed with untargeted GC-MS. The interpretation of the data was enhanced by the use of two different cell-lines and supports aspartate aminotransferase as a target. In addition, the data suggest an unexpected off-target effect on glutamate decarboxylase. The results exemplify the potency of metabolomics to provide insight into both mode of action and off-target effects of drug candidates.

show abstract