Investigation of interaction between human plasmatic albumin and potential fluorinated anti-trypanosomal drugs

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The interaction between four antiparasitic drugs (benznidazole (BZL), metronidazole (MTZ), nifurtimox (NFX) and megazol (MZ)) with human serum albumin (HSA), the main vehicle of biodistribution of xenobiotics, hydrophobic, small and endogenous molecules in the bloodstream, was evaluated by multiple spectroscopic techniques and theoretical calculations. In all cases quenching of the fluorescence of HSA by these drugs involve a static mechanism, due to ground state association. There is just one main binding site in HSA for these four ligands (Sudlow's site I); binding is spontaneous, moderate, does not have any effect on the polarity around the Tyr and Trp residues and does not perturb significantly the secondary structure of the protein. Molecular docking studies suggest hydrogen bonding and hydrophobic interactions as the main binding forces, i.e., BZL associates with the Trp-214 residue via hydrophobic interactions and with Gln-220, Arg-221 and Glu-449 residues via hydrogen bonding; whereas MTZ associates with Leu-197 and Leu-480 residues via hydrophobic interactions and with Trp-214, Glu-449 and Ser-453 via hydrogen bonding. Furthermore, electrostatic interactions were also suggested for HSA:MZ and HSA:NFX.

Section: Resultssupporting

confidence: 67%

Multiple Spectroscopic and Theoretical Approaches to Study the Interaction between HSA and the Antiparasitic Drugs: Benznidazole, Metronidazole, Nifurtimox and Megazol

Chaves¹,

Ferreira²,

Silva³

et al. 2018

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“…On the other hand, aromatic carboxylic acids like ibuprofen and aryl propionic acids generally bind in the subdomain IIIA, also known as Sudlow's site II. 19,20 In the present work the six 2-alkylamino-1,4-nahthoquinone derivatives shown in Figure 1 have not yet been described in the literature. The activity of these naphthoquinone derivatives was evaluated against four Gram-positive (Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus and Bacillus cereus) and five Gram-negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae positive β-lactamase) bacteria strain.…”

Section: Introductionmentioning

confidence: 90%

“…31 Further details on molecular docking calculation were already reported in previous publications. 20,32…”

Section: Molecular Docking Analysismentioning

confidence: 99%

Antibacterial Activity of 2-Amino-1,4-naphthoquinone Derivatives Against Gram‑Positive and Gram-Negative Bacterial Strains and Their Interaction with Human Serum Albumin

Silva

Chaves

Paiva

et al. 2020

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A series of 2-amino-1,4-naphthoquinone derivatives (NQA-NQF) was synthesized by alternative methods (ultrasonication and microwave irradiation), with yields ranging from 40 to 71%, and without the need of further recrystallization. Each compound was evaluated against four Gram-positive (Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus and Bacillus cereus) and five Gram-negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae positive β-lactamase) bacteria strains. The NQF was the most active amino-naphthoquinone derivative with minimum inhibitory concentration (MIC) of 31.2 µg mL-1 against K. pneumoniae positive β-lactamase (a common intestinal bacteria which can cause life-threatening infections). On the other hand, NQA and NQC showed good activity as a potential antibiotic for the bacteria strains assayed, except for K. pneumoniae. In addition, the affinity of these three most active compounds (NQA, NQC, and NQF) for human serum albumin (HSA) was evaluated employing multiple spectroscopic techniques (steady-state, time-resolved, and synchronous fluorescence, as well as circular dichroism), combined with theoretical calculations (molecular docking). The interaction HSA:2-amino-1,4-naphthoquinones occurs spontaneously and moderately inside the subdomain IIA (Sudlow's site I) via hydrogen bonding and van der Waals forces.

“…16 More details on the molecular docking procedures can be found in previous publications. 18,19 Experimental analysis…”

Section: Molecular Docking Analysismentioning

confidence: 99%

“…The α-helical contents of HSA without and in the presence of a ligand were calculated from the molar residual ellipticity (MRE) values at 208 (equation 7) and 222 nm (equation 8): 18,24 (7) (8)…”

Section: Circular Dichroism Analysismentioning

confidence: 99%

In vitro Analysis of the Interaction between Human Serum Albumin and Semi‑Synthetic Clerodanes

Chaves¹,

Echevarrı́a²,

Esteves-Souza³

et al. 2018

The interaction between HSA and two semi-synthetic potential anti-cancer agents derived from trans-dehydrocrotonin-methyl-hydrazone (MHDCTN) and phenyl-hydrazone (PHDCTN) was evaluated under physiological conditions at 296, 303 and 310 K by multi-spectroscopic techniques and molecular docking calculations. Steady state fluorescence quenching indicated a ground state association (static quenching) for both samples; however, the quenching induced by PHDCTN was not essentially static and can be accompanied by a dynamic quenching mechanism. The binding is strong (modified Stern-Volmer binding constant (K a ) ca. 10 5 M -1 ), causing a very weak perturbation on the secondary structure of the protein and there is just one main binding site for both samples (Sudlow's site I). Molecular docking results suggested hydrogen bonding and hydrophobic interactions as the main binding forces for both samples.