Underlying the Mechanism of 5-Fluorouracil and Human Serum Albumin Interaction: A Biophysical Study

Chinnathambi, Shanmugavel; Karthikeyan, S.; Kesherwani, Manish; Velmurugan, D.; Hanagata, Nobutaka

doi:10.4172/2161-0398.1000214

Cited by 21 publications

(20 citation statements)

References 24 publications

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“…Figure 3(a) shows the emission decay profile of free HSA and HSA-coumarin derivative complex; each point consists of average photons of respective wavelengths. All the recorded emission profiles of HSA and HSA complex followed the multiexponential decay kinetics, and the average lifetime decay for free HSA was found to be 4.83 ns which is almost equal to previously reported values [21,23]. However, in the case of HSA-coumarin derivative complex, the decay is slightly faster compared to that of free HSA, and the average estimation of the HSA complex is 4.67 ns ( Table 2).…”

Section: Time-resolved Emission Spectroscopy Studies (Tres) Andsupporting

confidence: 78%

“…From Figure 4, it is observed that there is a decrease in intensity maxima while adding the coumarin derivative into free HSA, and the quenching in both peak 1 and peak 2 may be due to the presence of the coumarin derivative, suggesting that the compound may be nearby the HSA chromophore. ese results conclude that there may be slight confirmation changes in HSA due to the presence of the coumarin derivative [23,24].…”

Section: Excitation-emission Matrix (Eem) Analysismentioning

confidence: 73%

“…Figure 5(a) shows the spectrum of free HSA and HSA-coumarin derivative complex, and the amide I peak of HSA is lying between 1600 and 1700 cm −1 and amide II region is almost in 1558 cm −1 , which is almost similar to the secondary Journal of Spectroscopy structure of proteins. Comparing these two bands, amide I is strong (1644 cm −1 ) as shown in Figure 5(a), and also while adding the coumarin derivative into free HSA, there is a decrease observed in the absorption of amide I maxima, which may be due to the coumarin derivative disturbance of the HSA amide region [21,23,24].…”

Section: Ftir Spectroscopy Studiesmentioning

confidence: 84%

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4-Hydroxycoumarin Derivative:N-(diphenylmethyl)-2-[(2-oxo-2H-chromen-4-yl)oxy]acetamide Interaction with Human Serum Albumin

Chinnathambi

Karthikeyan

Mangaiyarkarasi

et al. 2018

Journal of Spectroscopy

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In this study, the interaction between the coumarin derivative: N-(diphenylmethyl)-2-[(2-oxo-2H-chromen-4-yl)oxy]acetamide, biologically active drug, and human serum albumin (HSA) was investigated by using various optical spectroscopy techniques along with the computational technique. The results of steady-state fluorescence spectroscopy show that the static quenching occurred while increasing the coumarin drug concentration into HSA. Also, the binding constant (K) and thermodynamical parameters of enthalpy change (ΔH°), entropy change (ΔS°), and Gibbs free energy change (ΔG°) were calculated at different temperatures (293 K, 298 K, and 303 K). The results are in good agreement with those of molecular docking studies, and also, the docking study was carried out to understand the hydrogen bonding and hydrophobic interaction between human serum albumin and coumarin derivative. In addition to the docking, charge distribution analysis was done to understand the internal stability of coumarin derivative active sites of human serum albumin. Further time-resolved emission spectroscopy (TRES) studies were carried out between free HSA and HSA-coumarin complex, and the result confirms the presence of the drug in the protein molecule without cytotoxicity.

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Section: Time-resolved Emission Spectroscopy Studies (Tres) Andsupporting

confidence: 78%

Section: Excitation-emission Matrix (Eem) Analysismentioning

confidence: 73%

Section: Ftir Spectroscopy Studiesmentioning

confidence: 84%

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4-Hydroxycoumarin Derivative:N-(diphenylmethyl)-2-[(2-oxo-2H-chromen-4-yl)oxy]acetamide Interaction with Human Serum Albumin

Chinnathambi

Karthikeyan

Mangaiyarkarasi

et al. 2018

Journal of Spectroscopy

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“…5-fluorouracil (5-FU), an analog of pyrimidine, is one of the most effective antineoplastic agents, which shows remarkably enhanced inhibitory effects against a wide range of solid tumors 1 – 3 . 5-FU restrains the proliferation of cancer cells by inhibiting thymidylate synthase, and incorporating its metabolites into RNA and DNA 4 . Nonetheless, the inappropriate oral absorption and reduced bioavailability of 5-FU frequently lead to disappointing clinical therapeutic outcomes 5 – 7 .…”

Section: Introductionmentioning

confidence: 99%

Targeted delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells overexpressing epithelial growth factor receptor (EGFR) using virus-like nanoparticles

Gan

Rullah

Yong

et al. 2020

Sci Rep

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Chemotherapy is widely used in cancer treatments. However, non-specific distribution of chemotherapeutic agents to healthy tissues and normal cells in the human body always leads to adverse side effects and disappointing therapeutic outcomes. Therefore, the main aim of this study was to develop a targeted drug delivery system based on the hepatitis B virus-like nanoparticle (VLNP) for specific delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells expressing epithelial growth factor receptor (EGFR). 5-FA was synthesized from 5-fluorouracil (5-FU), and it was found to be less toxic than the latter in cancer cells expressing different levels of EGFR. The cytotoxicity of 5-FA increased significantly after being conjugated on the VLNP. A cell penetrating peptide (CPP) of EGFR was displayed on the VLNP via the nanoglue concept, for targeted delivery of 5-FA to A431, HT29 and HeLa cells. The results showed that the VLNP displaying the CPP and harboring 5-FA internalized the cancer cells and killed them in an EGFR-dependent manner. This study demonstrated that the VLNP can be used to deliver chemically modified 5-FU derivatives to cancer cells overexpressing EGFR, expanding the applications of the VLNP in targeted delivery of chemotherapeutic agents to cancer cells overexpressing this transmembrane receptor.

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“…The effects of PAC' binding to HSA, associated with major conformational changes, unfolding of the structure and significant increases of the hydrodynamic volume of the PAC-HSA complex [66], support the assumption of possible allosteric interactions when co-administered with other drugs. Moreover, indications for 5-FU to cause conformational changes in HSA have already been documented [67]. Therefore, allosteric changes induced by PAC and 5-FU on HSA could be one cause for the detected DDI.…”

Section: Discussionmentioning

confidence: 91%

Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro

et al. 2020

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Flucloxacillin (FLU), an isoxazolyl penicillin, is widely used for the treatment of different bacterial infections in intensive care units (ICU). Being highly bound to plasma proteins, FLU is prone to drug-drug interactions (DDI) when administered concurrently with other drugs. As FLU is binding to both Sudlow’s site I and site II of human serum albumin (HSA), competitive and allosteric interactions with other drugs, highly bound to the same sites, seem conceivable. Knowledge about interaction(s) of FLU with the widely used anticancer agents paclitaxel (PAC), imatinib (IMA), and 5-fluorouracil (5-FU is scarce. The effects of the selected anticancer agents on the unbound fraction of FLU were evaluated in pooled plasma as well as in HSA and α-1-acid glycoprotein (AGP) samples, the second major drug carrier in plasma. FLU levels in spiked samples were analyzed by LC-MS/MS after ultrafiltration. Significant increase in FLU unbound fraction was observed when in combination with PAC and IMA and to a lesser extent with 5-FU. Furthermore, significant binding of FLU to AGP was observed. Collectively, this is the first study showing the binding of FLU to AGP as well as demonstrating a significant DDI between PAC/IMA/5-FU and FLU.

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Underlying the Mechanism of 5-Fluorouracil and Human Serum Albumin Interaction: A Biophysical Study

Cited by 21 publications

References 24 publications

4-Hydroxycoumarin Derivative:N-(diphenylmethyl)-2-[(2-oxo-2H-chromen-4-yl)oxy]acetamide Interaction with Human Serum Albumin

4-Hydroxycoumarin Derivative:N-(diphenylmethyl)-2-[(2-oxo-2H-chromen-4-yl)oxy]acetamide Interaction with Human Serum Albumin

Targeted delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells overexpressing epithelial growth factor receptor (EGFR) using virus-like nanoparticles

Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro

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