Physicochemical, pharmacokinetic, efficacy and toxicity profiling of a potential nitrofuranyl methyl piperazine derivative IIIM-MCD-211 for oral tuberculosis therapy via in-silico – in-vitro – in-vivo approach

Magotra, Asmita; Sharma, Ashish; Singh, Samsher; Ojha, Probir Kumar; Kumar, Sunil; Bokolia, Naveen Prakash; Wazir, Priya; Sharma, Shweta; Khan, Inshad Ali; Singh, Parvinder Pal; Vishwakarma, Ram A.; Singh, Gurdarshan; Nandi, Utpal

doi:10.1016/j.pupt.2017.11.006

Cited by 23 publications

(30 citation statements)

References 33 publications

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“…The concentration of rottlerin was measured by this new LC–MS/MS method, whereas standards for specific experiments were measured by our in-house HPLC–UV or LC–MS/MS methods. We performed the above-mentioned studies using our earlier reported protocols − and detailed methodologies for each parameter are described in the Supporting Information.…”

Section: Materials and Methodsmentioning

confidence: 99%

Pharmacokinetic Assessment of Rottlerin from Mallotus philippensis Using a Highly Sensitive Liquid Chromatography–Tandem Mass Spectrometry-Based Bioanalytical Method

et al. 2021

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Rottlerin is a key bioactive phytoconstituent present in the pericarp of Mallotus philippensis. It shows promising multifaceted pharmacological actions against cancer. However, there is hardly any report for the quantification of rottlerin in the biological matrix and on its pharmacokinetic behavior. Therefore, we aimed in the present study to assess selective in vitro ADME properties and in vivo pharmacokinetics of isolated and characterized rottlerin using a newly developed and validated liquid chromatography−tandem mass spectrometry-based highly sensitive bioanalytical method. The method was found to be simple (mobile phase and analytical column), sensitive (1.9 ng/ mL), and rapid (run time of 2.5 min). All the validation parameters were within the acceptable criteria of the United States Food and Drug Administration's bioanalytical method validation guideline. The method was found to be very useful to assess lipophilicity, plasma stability, metabolic stability, plasma protein binding of rottlerin, as well as its oral and intravenous pharmacokinetics in mice. Rottlerin showed a number of drug-like pharmacokinetic properties (in vitro). Moreover, it displayed an excellent half-life (>2 h) and oral bioavailability (>35%) as compared to other members of natural phenolics. The present study is the first-time report of in vitro ADME properties and in vivo preclinical pharmacokinetics of rottlerin. The generated information is very much useful for its further development as a phytotherapeutics toward cancer therapy.

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Section: Materials and Methodsmentioning

confidence: 99%

Pharmacokinetic Assessment of Rottlerin from Mallotus philippensis Using a Highly Sensitive Liquid Chromatography–Tandem Mass Spectrometry-Based Bioanalytical Method

et al. 2021

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“…Tandem mass spectrophotometer with electrospray ionization (ESI) source was operated in positive mode and quantitation of PMBA was performed on multiple reactions monitoring (MRM) mode with parent ion/product ion transition pairs of 558.4 > 118.9. Plasma concentrations of PMBA at respective time points were obtained and calculation was done for various pharmacokinetic parameters (C max , maximum plasma concentration; T max , time to reach maximum plasma concentration; T 1/2 , elimination half-life; AUC0-t, area under the curve for plasma concentration from zero to the last measurable plasma sample time; AUC0-∞, area under the curve for plasma concentration from zero to time infinity; V d , volume of distribution; Cl, clearance) by non-compartmental analysis using PK solution software (Summit Research Services, Colorado, USA) ( Yempalla et al., 2015 ; Magotra et al., 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Synergistic combination of PMBA and 5-fluorouracil (5-FU) in targeting mutant KRAS in 2D and 3D colorectal cancer cells

Qayum

Magotra

Shah

et al. 2022

Heliyon

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“…In vitro P -gp induction by the candidates was investigated based on intracellular accumulation of rhodamine 123 (Rh123) in LS180 cells according to our previously developed protocol. , In brief, cells (20 000 cells/well) were seeded in 96-well plates and then allowed to grow for the next 24 h. Treatment was given for 48 h with rifampicin as the standard P -gp inducer (5 μM) and individual candidates (5 μM) by adding to complete media. The test compound was then removed, and the cells were incubated with Hank’s buffer for 30 min and further incubated for 90 min in the same media containing Rh123 as a P -gp substrate (10 μM).…”

Section: Materials and Methodsmentioning

confidence: 99%

Effect of Natural Phenolics on Pharmacokinetic Modulation of Bedaquiline in Rat to Assess the Likelihood of Potential Food–Drug Interaction

Kotwal

Dogra

Sharma

et al. 2020

J. Agric. Food Chem.

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Bedaquiline (TMC-207) is a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB). Moreover, there is a present and growing concern for natural-product-mediated drug interaction, as these are inadvertently taken by patients as a dietary supplement, food additive, and medicine. In the present study, we investigated the impact of 20 plant-based natural products, typically phenolics, on in vivo oral bedaquiline pharmacokinetics, as previous studies are lacking. Three natural phenolics were identified that can significantly enhance the oral exposure of bedaquiline upon coadministration. We further investigated the possible role of all of the phytochemicals on in vitro P-glycoprotein (P-gp) induction and inhibition and CYP3A4 inhibition in a single platform as bedaquiline is the substrate for both P-gp and CYP3A4. In conclusion, curcumin, CC-I (3′,5–dihydroxyflavone-7-O-β-d-galacturonide-4′-O-β-d-glucopyranoside), and 6-gingerol should not be coadministered with bedaquiline to avoid untoward drug interactions and, subsequently, its dose-dependent adverse effects.

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Physicochemical, pharmacokinetic, efficacy and toxicity profiling of a potential nitrofuranyl methyl piperazine derivative IIIM-MCD-211 for oral tuberculosis therapy via in-silico – in-vitro – in-vivo approach

Cited by 23 publications

References 33 publications

Pharmacokinetic Assessment of Rottlerin from Mallotus philippensis Using a Highly Sensitive Liquid Chromatography–Tandem Mass Spectrometry-Based Bioanalytical Method

Pharmacokinetic Assessment of Rottlerin from Mallotus philippensis Using a Highly Sensitive Liquid Chromatography–Tandem Mass Spectrometry-Based Bioanalytical Method

Synergistic combination of PMBA and 5-fluorouracil (5-FU) in targeting mutant KRAS in 2D and 3D colorectal cancer cells

Effect of Natural Phenolics on Pharmacokinetic Modulation of Bedaquiline in Rat to Assess the Likelihood of Potential Food–Drug Interaction

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