Elucidation of the interaction of human serum albumin with anti‐cancer sipholane triterpenoid from the Red Sea sponge

Ali, Mushir; Amina, Musarat; Al‐Lohedan, Hamad A.; Musayeib, Nawal M. Al

doi:10.1002/bio.3172

Cited by 14 publications

(7 citation statements)

References 30 publications

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“…The values obtained for R 0 and r 0 are much less than 8 nm which is essential for FRET , to take place between donor (Trp214) and the specific molybdenum complex (acceptor) bound to HSA (as found from molecular docking study). Furthermore, the obtained r 0 value obeys the relation 0.5 R 0 < r 0 < 1.5 R 0 , which implies that the energy transfer takes place in the interaction with high probability. ,, …”

Section: Results and Discussionmentioning

confidence: 59%

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Mo(VI) Potential Metallodrugs: Explaining the Transport and Cytotoxicity by Chemical Transformations

et al. 2022

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The transport and cytotoxicity of molybdenum-based drugs have been explained with the concept of chemical transformation, a very important idea in inorganic medicinal chemistry that is often overlooked in the interpretation of the biological activity of metal-containing systems. Two monomeric, [MoO2(L1)(MeOH)] (1) and [MoO2(L2)(EtOH)] (2), and two mixed-ligand dimeric MoVIO2 species, [{MoO2(L1–2)}2(μ-4,4′-bipy)] (3–4), were synthesized and characterized. The structures of the solid complexes were solved through SC-XRD, while their transformation in water was clarified by UV–vis, ESI-MS, and DFT. In aqueous solution, 1–4 lead to the penta-coordinated [MoO2(L1–2)] active species after the release of the solvent molecule (1 and 2) or removal of the 4,4′-bipy bridge (3 and 4). [MoO2(L1–2)] are stable in solution and react with neither serum bioligand nor cellular reductants. The binding affinity of 1–4 toward HSA and DNA were evaluated through analytical and computational methods and in both cases a non-covalent interaction is expected. Furthermore, the in vitro cytotoxicity of the complexes was also determined and flow cytometry analysis showed the apoptotic death of the cancer cells. Interestingly, μ-4,4′-bipy bridged complexes 3 and 4 were found to be more active than monomeric 1 and 2, due to the mixture of species generated, that is [MoO2(L1–2)] and the cytotoxic 4,4′-bipy released after their dissociation. Since in the cytosol neither the reduction of MoVI to MoV/IV takes place nor the production of reactive oxygen species (ROS) through Fenton-like reactions of 1–4 with H2O2 occurs, the mechanism of cytotoxicity should be attributable to the direct interaction with DNA that happens with a minor-groove binding which results in cell death through an apoptotic mechanism.

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Section: Results and Discussionmentioning

confidence: 59%

“…Furthermore, the obtained r 0 value obeys the relation 0.5R 0 < r 0 < 1.5R 0 , which implies that the energy transfer takes place in the interaction with high probability. 108,110,111 DNA Binding. Absorption Titration.…”

Section: ■ Introductionmentioning

confidence: 99%

Mo(VI) Potential Metallodrugs: Explaining the Transport and Cytotoxicity by Chemical Transformations

et al. 2022

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“…HSA and its BSA counterpart are among the most studied protein and its binding with various types of substances is well known [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Understanding the binding mechanism of a drug is necessary to understand its pharmacokinetics and pharmacodynamics.…”

Section: Introductionmentioning

confidence: 99%

“…Understanding the binding mechanism of a drug is necessary to understand its pharmacokinetics and pharmacodynamics. Albumin binds with several ligands at different extents and the binding level of a compound may vary from very strong to weak depending on the various affinities responsible for the interaction [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Detailed Experimental and In Silico Investigation of Indomethacin Binding with Human Serum Albumin Considering Primary and Secondary Binding Sites

et al. 2023

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The interaction of indomethacin with human serum albumin (HSA) has been studied here considering the primary and secondary binding sites. The Stern–Volmer plots were linear in the lower concentration range of indomethacin while a downward curvature was observed in the higher concentration range, suggesting the presence of more than one binding site for indomethacin inside HSA due to which the microenvironment of the fluorophore changed slightly and some of its fraction was not accessible to the quencher. The Stern–Volmer quenching constants (KSV) for the primary and secondary sites were calculated from the two linear portions of the Stern–Volmer plots. There was around a two-fold decrease in the quenching constants for the low-affinity site as compared to the primary binding site. The interaction takes place via a static quenching mechanism and the KSV decreases at both primary and secondary sites upon increasing the temperature. The binding constants were also evaluated, which show strong binding at the primary site and fair binding at the secondary site. The binding was thermodynamically favorable with the liberation of heat and the ordering of the system. In principle, hydrogen bonding and Van der Waals forces were involved in the binding at the primary site while the low-affinity site interacted through hydrophobic forces only. The competitive binding was also evaluated using warfarin, ibuprofen, hemin, and a warfarin + hemin combination as site markers. The binding profile remained unchanged in the presence of ibuprofen, whereas it decreased in the presence of both warfarin and hemin with a straight line in the Stern–Volmer plots. The reduction in the binding was at a maximum when both warfarin and hemin were present simultaneously with the downward curvature in the Stern–Volmer plots at higher concentrations of indomethacin. The secondary structure of HSA also changes slightly in the presence of higher concentrations of indomethacin. Molecular dynamics simulations were performed at the primary and secondary binding sites of HSA which are drug site 1 (located in the subdomain IIA of the protein) and the hemin binding site (located in subdomain IB), respectively. From the results obtained from molecular docking and MD simulation, the indomethacin molecule showed more binding affinity towards drug site 1 followed by the other two sites.

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“…The longer stay of a drug may give rise to more side effects, whereas a shorter stay might restrict the desired therapeutic effects. Moreover, drugs or any other ligand, when interacting with albumins, show the diverse range of effects on the latter; for instance, they (i) may lead to denaturation or unfolding, (ii) might trigger some partial impact on the structure and stability, (iii) did not affect their structure at all or (iv) can increase the stability of the former, depending on the structural and binding properties of the former [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Thus, it is important to know the interaction of a drug with serum albumin.…”

Section: Introductionmentioning

confidence: 99%

Experimental and Computational Investigation on the Interaction of Anticancer Drug Gemcitabine with Human Plasma Protein: Effect of Copresence of Ibuprofen on the Binding

Ali

Al‐Lohedan

2022

Molecules

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The interaction of common anticancer drug gemcitabine with human serum albumin (HSA) has been studied in detail. The effect of an omnipresent nonsteroidal anti-inflammatory drug ibuprofen was also seen on the binding of HSA and gemcitabine. A slight hyperchromic shift in the difference UV-visible absorption spectra of HSA on the addition of gemcitabine gave a primary idea of the possible complex formation between them. The inner filter effect, which happens due to the significant absorbance of the ligand at the excitation and/or emission wavelengths, played an important role in the observed fluorescence quenching of HSA by gemcitabine that can be understood by comparing the observed and corrected fluorescence intensities obtained at λex = 280 nm and 295 nm. Gemcitabine showed weak interaction with HSA, which took place via a dynamic quenching mechanism with 1:1 cooperative binding between them. Secondary structural analysis, based on circular dichroism (CD) spectroscopy, showed that low concentrations of gemcitabine did not affect the native structure of protein; however, higher concentrations affected it slightly with partial unfolding. For understanding the binding site of gemcitabine within HSA, both experimental (using site markers, warfarin and ibuprofen) as well as computational methods were employed, which revealed that the gemcitabine binding site is located between the interface of subdomain IIA and IIB within the close proximity of the warfarin site (drug site 1). The effect of ibuprofen on the binding was further elaborated because of the possibility of its coexistence with gemcitabine in the prescription given to the cancer patients, and it was noticed that, ibuprofen, even present in high amounts, did not affect the binding efficacy of gemcitabine with HSA. DFT analyses of various conformers of gemcitabine obtained from its docking with various structures of HSA (free and bounded with site markers), show that the stability of the gemcitabine molecule increased slightly after binding with ibuprofen-complexed HSA. Both experimental as well as computational results were in good agreement with each other.

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Elucidation of the interaction of human serum albumin with anti‐cancer sipholane triterpenoid from the Red Sea sponge

Cited by 14 publications

References 30 publications

Mo(VI) Potential Metallodrugs: Explaining the Transport and Cytotoxicity by Chemical Transformations

Mo(VI) Potential Metallodrugs: Explaining the Transport and Cytotoxicity by Chemical Transformations

Detailed Experimental and In Silico Investigation of Indomethacin Binding with Human Serum Albumin Considering Primary and Secondary Binding Sites

Experimental and Computational Investigation on the Interaction of Anticancer Drug Gemcitabine with Human Plasma Protein: Effect of Copresence of Ibuprofen on the Binding

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