Chiral Aspects of Local Anesthetics

Cizmáriková, R; Čiẑmárik, J; Valentová, Jindra; Habala, Ladislav; Markuliak, Mário

doi:10.3390/molecules25122738

Cited by 22 publications

(20 citation statements)

References 87 publications

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“…Lidocaine is a local anesthetic drug derived from cocaine, and widely used in clinical application such as anti-bacteria, antiinflammation, local skin anesthesia and so on (Caracas et al, 2009;Adler et al, 2017;Cizmarikova et al, 2020). An increasing number of evidences have demonstrated that lidocaine could affect the development of multiple tumors including ovarian and breast cancer (Gao et al, 2018;Khan et al, 2019;Liu et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer

Sun

Zhang

2021

Front. Pharmacol.

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Ovarian and breast cancer are prevalent female malignancies with increasing occurrence incidence and metastasis, significantly affecting the health and life quality of women globally. Anesthetic lidocaine has presented anti-tumor activities in the experimental conditions. However, the effect of lidocaine on ovarian and breast cancer remains elusive. We identified the important function of lidocaine in enhancing ferroptosis and repressing progression of ovarian and breast cancer. Our data showed that lidocaine further repressed erastin-inhibited ovarian and breast cancer cell viabilities. The treatment of lidocaine induced accumulation of Fe2+, iron and lipid reactive oxygen species (ROS) in ovarian and breast cancer cells. The ovarian and breast cancer cell proliferation was suppressed while cell apoptosis was induced by lidocaine in vitro. Lidocaine attenuated invasion and migration of ovarian and breast cancer cells as well. Regarding the mechanism, we found that lidocaine downregulated solute carrier family 7 member 11 (SLC7A11) expression by enhancing microRNA-382-5p (miR-382-5p) in the cells. The inhibition of miR-382-5p blocked lidocaine-induced ferroptosis of ovarian and breast cancer cells. MiR-382-5p/SLC7A11 axis was involved in lidocaine-mediated inhibition of ovarian and breast cancer cell proliferation in vitro. The miR-382-5p expression was down-regulated but SLC7A11 expression was up-regulated in clinical ovarian and breast cancer samples. Furthermore, the treatment of lidocaine repressed tumor growth of ovarian cancer cells in vivo, in which the miR-382-5p expression was increased while SLC7A11 expression was decreased. Consequently, we concluded that the lidocaine promoted ferroptosis by miR-382-5p/SLC7A11 axis in ovarian and breast cancer cells. The clinical value of lidocaine in the treatment of ovarian and breast cancer deserves to be proved in detail.

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Section: Introductionmentioning

confidence: 99%

Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer

Sun

Zhang

2021

Front. Pharmacol.

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“…The separation was initially developed on a 50.2 cm x 50 μm fused silica capillary, investigating the effects of the pH, the concentration of BGE components (buffering agent, cationic additives) and TM-β-CD on the migration time and resolution R S of the Ibu enantiomers. R S was calculated according to the equation R S = 1.18 × (t m1 − t m2 ) / w 0.5(1) + w 0.5 (2) (1…”

Section: Methods Developmentmentioning

confidence: 99%

Investigation of isomerization of dexibuprofen in a ball mill using chiral capillary electrophoresis

et al. 2021

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Besides the racemate, the S-enantiomer of ibuprofen (Ibu) is used for the treatment of inflammation and pain. Since the configurational stability of S-Ibu in solid state is of interest, it was studied by means of ball milling experiments. For the evaluation of the enantiomeric composition, a chiral CE method was developed and validated according to the ICH guideline Q2(R1). The addition of Mg 2+ , Ca 2+ , or Zn 2+ ions to the background electrolyte (BGE) was found to improve Ibu enantioresolution. Chiral separation of Ibu enantiomers was achieved on a 60.2 cm (50.0 cm effective length) x 75 μm fused-silica capillary using a background electrolyte (BGE) composed of 50 mM sodium acetate, 10 mM magnesium acetate tetrahydrate, and 35 mM heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD) as chiral selector. The quantification of R-Ibu in the mixture was performed using the normalization procedure. Linearity was evaluated in the range of 0.68-5.49% R-Ibu (R 2 = 0.999), recovery was found to range between 97 and 103%, the RSD of intra-and interday precision below 2.5%, and the limit of quantification for R-in S-Ibu was calculated to be 0.21% (extrapolated) and 0.15% (dilution of racemic ibuprofen), respectively. Isomerization of S-Ibu was observed under basic conditions by applying long milling times and high milling frequencies.

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“…The analytical methods to monitor the pharmacokinetics of local anesthetics were recently reviewed [ 6 ]. The changes in the pure enantiomers for different anesthetics, such as bupivacaine, mepivacaine, prilocaine, and ropivacaine, were studied.…”

Section: Chiral Analysis In Pharmacokineticsmentioning

confidence: 99%

“…In the case of LC, several CSPs based on cyclodextrins, macrocyclic antibiotics, or substituted carbamates from cellulose and amylose were tested. It was concluded that although the use of local anesthetics in an enantiomerically pure form has advantageous properties in terms of its activity and lowtoxicity, its potential has not yet been fully studied and verified [ 6 ]. The enantioselective methods to study pharmacokinetics and pharmaceutical formulations of venlafaxine were also recently revised, which encompass LC-UV, LC-MS, LC-MS/MS, and capillary electrophoresis methods [ 44 ].…”

Section: Chiral Analysis In Pharmacokineticsmentioning

confidence: 99%

“…Interestingly, 20 out of 35 pharmaceuticals approved by the FDA in 2020 are chiral [ 5 ], and an increasing trend in authorization requests for chiral drugs has been observed. In recent years, a growing interest in enantiomerically pure substances has been observed in pharmacology and medicinal chemistry, because beyond the advantages of the drug administration as pure enantiomers, toxicity can be associated to the inactive enantiomer [ 6 , 7 ]. The objective of launching enantiomerically pure compounds has been achieved by resorting to the practice of chiral switches or by manufacturing a new single enantiomeric drug [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Enantioselectivity in Drug Pharmacokinetics and Toxicity: Pharmacological Relevance and Analytical Methods

et al. 2021

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Enzymes, receptors, and other binding molecules in biological processes can recognize enantiomers as different molecular entities, due to their different dissociation constants, leading to diverse responses in biological processes. Enantioselectivity can be observed in drugs pharmacodynamics and in pharmacokinetic (absorption, distribution, metabolism, and excretion), especially in metabolic profile and in toxicity mechanisms. The stereoisomers of a drug can undergo to different metabolic pathways due to different enzyme systems, resulting in different types and/or number of metabolites. The configuration of enantiomers can cause unexpected effects, related to changes as unidirectional or bidirectional inversion that can occur during pharmacokinetic processes. The choice of models for pharmacokinetic studies as well as the subsequent data interpretation must also be aware of genetic factors (such as polymorphic metabolic enzymes), sex, patient age, hepatic diseases, and drug interactions. Therefore, the pharmacokinetics and toxicity of a racemate or an enantiomerically pure drug are not equal and need to be studied. Enantioselective analytical methods are crucial to monitor pharmacokinetic events and for acquisition of accurate data to better understand the role of the stereochemistry in pharmacokinetics and toxicity. The complexity of merging the best enantioseparation conditions with the selected sample matrix and the intended goal of the analysis is a challenge task. The data gathered in this review intend to reinforce the importance of the enantioselectivity in pharmacokinetic processes and reunite innovative enantioselective analytical methods applied in pharmacokinetic studies. An assorted variety of methods are herein briefly discussed.

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Chiral Aspects of Local Anesthetics

Cited by 22 publications

References 87 publications

Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer

Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer

Investigation of isomerization of dexibuprofen in a ball mill using chiral capillary electrophoresis

Enantioselectivity in Drug Pharmacokinetics and Toxicity: Pharmacological Relevance and Analytical Methods

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