LC/Q-TOF MS and LC/QQQ MS based bioanalysis of a new ferrocene derivative as a potential anticancer lead with promising drug-like characteristics

Jogpethe, Ashish; Jadav, Tarang; Rajput, Niraj; Sahu, Amit Kumar; Das, Rudradip; Gupta, Astha; Shard, Amit; Sengupta, Pinaki

doi:10.1016/j.jchromb.2022.123469

Cited by 6 publications

(7 citation statements)

References 27 publications

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“…Absorbances were recorded for all the solutions having pH ranging from 1.6 to 12.00 at both acidic and basic λ max . Intersection point in the graph plotted for pH against absorbance for both λ max was considered as a pKa value (Jogpethe et al, 2022).…”

Section: Determination Of Pkamentioning

confidence: 99%

“…A total of 50 µL aliquots of plasma were collected at various time intervals (0, 15, 30, 60, and 120 min). Fenofibrate was used as a positive standard to ensure enzymatic activity of plasma (Jogpethe et al, 2022). The stability of the lead molecule was also checked in phosphate buffer solution having pH 7.4 following a similar procedure (Jogpethe et al, 2022).…”

Section: Plasma Stabilitymentioning

confidence: 99%

“…Fenofibrate was used as a positive standard to ensure enzymatic activity of plasma (Jogpethe et al, 2022). The stability of the lead molecule was also checked in phosphate buffer solution having pH 7.4 following a similar procedure (Jogpethe et al, 2022). The protein precipitation method with 450 µL acetonitrile was used for extracting the analyte from plasma samples.…”

Section: Plasma Stabilitymentioning

confidence: 99%

“…Verapamil was used as a positive standard to validate the enzymatic activity of HLM (Grbac, 2013). The stability of the molecule was also checked in the same system without NADPH (NADPH was replaced with phosphate buffer solution) (Jogpethe et al, 2022). The protein precipitation technique was used to process the samples with 450 µL acetonitrile and samples were subsequently analysed using the developed quantitation method.…”

Section: Metabolic Stabilitymentioning

confidence: 99%

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Comprehensive characterization and preclinical assessment of an imidazopyridine‐based anticancer lead molecule

Bulbule,

Jadav,

Rajput

et al. 2023

Drug Development Research

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Imidazopyridine scaffold holds significant pharmacological importance in the treatment of cancer. An in‐house synthesized imidazopyridine‐based molecule was found to have promising anticancer activity against breast cancer, lung cancer, and colon cancer. The molecule is an inhibitor of pyruvate kinase M2, the enzyme that elevates tumor growth, metastasis and chemoresistance by directly controlling tumor cell metabolism. Screening of the physicochemical properties of any lead molecules is essential to avoid failure in late‐stage drug development. In this research, the physicochemical properties of the molecule including log P, log D, pKa, and plasma protein binding were assessed to check its drug‐likeness. Plasma and metabolic stability of the molecule were also evaluated. Moreover, pharmacokinetic profiles of the lead molecule in Sprague‐Dawley rats and in vitro metabolite identification studies were also performed. Finally, an in silico software, Pro‐Tox‐II, was used to predict toxicity of the molecule and its metabolites. Log P, Log D (pH 7.4), pKa, and plasma protein binding of the molecule were found to be 2.03%, 2.42%, 10.4%, and 98%, respectively. The molecule was stable in plasma and metabolic conditions. A total of nine new metabolites were identified and characterized. Cmax and t½ of this molecule were found to be 4016 ± 313.95 ng/mL and 9.57 ± 3.05 h, respectively. Based on the previously reported study and this finding, the molecule can be considered as a promising anticancer lead with potential drug‐likeness properties. Further preclinical and clinical drug discovery studies may be initiated in continuation of this study in search of a potential anticancer lead.

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Section: Determination Of Pkamentioning

confidence: 99%

Section: Plasma Stabilitymentioning

confidence: 99%

Section: Plasma Stabilitymentioning

confidence: 99%

Section: Metabolic Stabilitymentioning

confidence: 99%

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Comprehensive characterization and preclinical assessment of an imidazopyridine‐based anticancer lead molecule

Bulbule,

Jadav,

Rajput

et al. 2023

Drug Development Research

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“…Preclinical studies mainly focus on in vitro and in vivo pharmacokinetics, pharmacodynamics and toxicological studies, which provide information regarding a new chemical entity’s safety and efficacy (Biswas et al, 2018; Nemani et al, 2018). In vitro studies including plasma stability, metabolic stability and plasma protein binding studies help in identifying the important inherent characteristics of a molecule (Jogpethe et al, 2022; Negi & Badola, 2018). In vivo preclinical studies generate preliminary information on the pharmacokinetic, pharmacodynamic and toxicological behavior of the molecule (Zagade et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Assessment of metabolic stability and pharmacokinetics by LC–MS/MS and establishment of the safe dose of IMID‐2, a novel anticancer molecule under drug discovery

Kumar

Jadav

Sahu

et al. 2023

Biomedical Chromatography

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Pyruvate kinase (PK) M2 activators ramp up glycolysis in cancer cells, leading to a reversal of the Warburg effect in cancer cells. A promising PKM2 activator molecule, IMID-2, developed by the National Institute of Pharmaceutical Education and Research-Ahmedabad showed promising anticancer activity against MCF-7 and COLO-205 cell lines, which represent breast and colon cancer. Its physicochemical properties, like solubility, ionization constant, partition coefficient and distribution constant, have already been established. Its metabolic pathway is also well established through in vitro and in vivo metabolite profiling and reported previously. In this study, we have evaluated the metabolic stability of IMID-2 using LC-MS/MS and investigated the safety aspect of the molecule through an acute oral toxicity study. In vivo studies in rats confirmed that the molecule is safe even at a dose level of 175 mg/kg. Furthermore, a pharmacokinetic study of IMID-2 was also carried out using LC-MS/MS to understand its absorption, distribution, metabolism, and excretion profile. The molecule was found to have promising bioavailability through the oral route. This research work is thus another step in the drug testing of this promising anticancer molecule. The molecule can be considered to be a potential anticancer lead based on the earlier report substantiated by current findings.

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LC-QQQ-MS based intracellular quantification of bictegravir in peripheral blood mononuclear cells and plasma

Jadav

Rajput

Sahu

et al. 2023

Analytical Biochemistry

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LC/Q-TOF MS and LC/QQQ MS based bioanalysis of a new ferrocene derivative as a potential anticancer lead with promising drug-like characteristics

Cited by 6 publications

References 27 publications

Comprehensive characterization and preclinical assessment of an imidazopyridine‐based anticancer lead molecule

Comprehensive characterization and preclinical assessment of an imidazopyridine‐based anticancer lead molecule

Assessment of metabolic stability and pharmacokinetics by LC–MS/MS and establishment of the safe dose of IMID‐2, a novel anticancer molecule under drug discovery

LC-QQQ-MS based intracellular quantification of bictegravir in peripheral blood mononuclear cells and plasma

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