Pharmacokinetic properties, in vitro metabolism and plasma protein binding of govaniadine an alkaloid isolated from Corydalis govaniana Wall

Marques, Lucas Maciel Mauriz; Callejon, Daniel R.; Pinto, Lidiane de Castro; Campos, Marcelo Lattarulo; Oliveira, Anderson Rodrigo Moraes de; Vessecchi, Ricardo; Adhikari, Achyut; Shrestha, Ram Lal; Peccinini, Rosângela Gonçalves; Lopes, Norberto P.

doi:10.1016/j.jpba.2016.09.003

Cited by 11 publications

(8 citation statements)

References 29 publications

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“…The validation of DPTM determination in plasma, tissue homogenates, urine and feces was conducted in terms of specificity, linearity, sensitivity, accuracy, precision, extraction recovery, matrix effect, stability and dilution integrity according to the EMEA guidelines [28,29].…”

Section: Methodsmentioning

confidence: 99%

A Validated HPLC-MS/MS Assay for 14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] Mutilin in Biological Samples and Its Pharmacokinetic, Distribution and Excretion via Urine and Feces in Rats

Liu

et al. 2019

Molecules

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14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] mutilin (DPTM), a novel pleuromutilin candidate with a substituted pyrimidine moiety, has been confirmed to possess excellent antibacterial activity against Gram-positive bacteria. To illustrate the pharmacokinetic profile after intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations with DPTM, as well as tissue distribution and excretion via urine and feces in vivo, a specific, sensitive and robust HPLC-MS/MS method was first developed to determine DPTM in rat plasma, various tissues, urine and feces. The plasma, tissues, urine and feces samples were treated by protein precipitation with acetonitrile using tiamulin fumarate as an internal standard (IS). This method which was achieved on an HPLC system detector equipped with an ESI interface, was sensitive with 5 ng/mL as the lower limit of detection and exhibited good linearity (R2 > 0.9900) in the range of 5–4000 ng/mL for plasma, various tissues, urine and feces, as well as intra-day precision, inter-day precision and accuracy. The matrix effects ranged from 94.2 to 109.7% with RSD ≤ 9.4% and the mean extraction recoveries ranged from 95.4 to 109.5% in plasma, tissue homogenates, urine and feces (RSD ≤ 9.9). After i.v., i.m. and p.o. administrations, DPTM was rapidly absorbed and metabolized in rats with the half-life (t1/2) of 1.70–1.86, 3.23–3.49 and 4.38–4.70 for 10, 25 and 75 mg/kg doses, respectively. The tissue distribution showed that DPTM was diffused into all the tested tissues, especially into the intestine and lung. Excretion via urine and feces studies demonstrated that DPTM was mainly excreted by feces after administration.

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Section: Methodsmentioning

confidence: 99%

A Validated HPLC-MS/MS Assay for 14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] Mutilin in Biological Samples and Its Pharmacokinetic, Distribution and Excretion via Urine and Feces in Rats

Liu

et al. 2019

Molecules

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“…Govaniadine was shown to possess some bioactivities such as urease inhibition activity and analgesic activity [ 11 , 12 ]. In addition, it was shown to possess pharmacokinetic properties such as in vitro metabolism and plasma protein binding [ 13 ], but its anticancer activity has not yet been studied. Therefore, in the present study in vitro cytotoxic activity and apoptotic effects of govaniadine on MCF-7 breast cancer cells were evaluated.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic and Apoptotic Effects of Govaniadine Isolated fromCorydalis govanianaWall. Roots on Human Breast Cancer (MCF-7) Cells

Sivakumaran

Samarakoon

Adhikari

et al. 2018

BioMed Research International

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Current breast cancer therapies have limitations in terms of increased drug resistance resulting in short-term efficacy, thus demanding the discovery of new therapeutic agents. In this study, cytotoxic activity and apoptotic effects of govaniadine isolated from Corydalis govaniana Wall. roots were determined on human breast cancer (MCF-7) cells. The SRB assay result revealed that govaniadine led to dose- and time-dependent cytotoxic effect in MCF-7 cells along with less cytotoxicity against MCF-10A cells. Govaniadine-induced apoptosis was also accompanied by upregulation of Bax, p53, and Survivin mRNA expression as assessed by real time PCR analysis. Flow cytometric analysis with Annexin V and PI staining indicated that govaniadine is a potent inducer of apoptosis in MCF-7 cell lines. Distinctive morphological changes contributed to apoptosis and DNA laddering were observed in govaniadine-treated MCF-7 cells. Caspase-7 was significantly activated in treated MCF-7 cells. Govaniadine-treated MCF-7 cells also showed enhanced levels of intracellular reactive oxygen species (ROS) and glutathione S-transferase (GST) and decreased levels of glutathione (GSH). The results indicate that govaniadine has potent and selective cytotoxic effects against MCF-7 cells and the potential to induce caspase 7 dependent apoptosis in MCF-7 cells by activation of pathways that lead to oxidative stress.

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“…11 These studies revealed significant analgesic activity for govaniadine, similar to that of ibuprofen, due to its potential binding to the COX-2 enzyme. 12 Furthermore, high and selective leishmanicidal activity, 13 antiurease activity, 10 and glucoronidase inhibition were reported. 14…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of the Ortho-Hydroxylated Protoberberines (S)-Govaniadine, (S)-Caseamine, and (S)-Clarkeanidine via a Solvent-Directed Pictet–Spengler Reaction

et al. 2018

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The common para regioselectivity in Pictet–Spengler reactions with dopamine derivatives is redirected to the ortho position by a simple change of solvents. In combination with a chiral auxiliary on nitrogen, this ortho-selective Pictet–Spengler produced the 1-benzyltetrahydroisoquinoline alkaloids (S)-crassifoline and (S)-norcrassifoline and the bioactive 1,2-dioxygenated tetrahydroprotoberberine alkaloids (S)-govaniadine, (S)-caseamine, and (S)-clarkeanidine with high enantiopurity. Ortho/para ratios up to 89:19 and diastereomeric ratios up to 85:15 were obtained during formation of the B-ring. The general applicability of this solvent-directed regioselectivity was demonstrated with a second Pictet–Spengler reaction as required for C-ring formation of caseamine (o/p = 14:86 in trifluoroethanol) and clarkeanidine (o/p = 86:14 in toluene).

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Pharmacokinetic properties, in vitro metabolism and plasma protein binding of govaniadine an alkaloid isolated from Corydalis govaniana Wall

Cited by 11 publications

References 29 publications

A Validated HPLC-MS/MS Assay for 14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] Mutilin in Biological Samples and Its Pharmacokinetic, Distribution and Excretion via Urine and Feces in Rats

A Validated HPLC-MS/MS Assay for 14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] Mutilin in Biological Samples and Its Pharmacokinetic, Distribution and Excretion via Urine and Feces in Rats

Cytotoxic and Apoptotic Effects of Govaniadine Isolated fromCorydalis govanianaWall. Roots on Human Breast Cancer (MCF-7) Cells

Total Synthesis of the Ortho-Hydroxylated Protoberberines (S)-Govaniadine, (S)-Caseamine, and (S)-Clarkeanidine via a Solvent-Directed Pictet–Spengler Reaction

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