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Spectroscopic and calorimetric analysis of the interaction between 9-hydroxy-5-methyl-12(H)-quino[3; 4-b][1; 4] benzothiazinium chloride with potential anticancer activity and main carrier plasma proteins. In vitro studies
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DOI：10.3389/fmolb.2026.1872215.png)
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Abstract
En 中文
Human serum albumin and α1 acid glycoprotein play a key role in the transport and distribution of many compounds in the human bloodstream. Investigating their interactions with drugs is an important part of the preliminary evaluation of the pharmacokinetic profile during the research and development of new drugs. 9-hydroxy-5-methyl-12(H)-quino[3; 4-b][1; 4]benzothiazinum chloride (Salt4) is a newly synthesized substance that demonstrated antiproliferative activity in vitro against human colon tumor and Lewis lung carcinoma cell lines. The aim of this study was to evaluate the interaction between Salt4 and HSA as well as AGP using spectroscopic and nanocalorimetric techniques and to assess the effect of Salt4 on the secondary and tertiary structure of these proteins. Spectrofluorescence spectroscopy were used to determine the Stern–Volmer constants (KS-V) and bimolecular quenching constants rate (kq). The association constants (Ka) and the number of binding site classes (nc) of the complexes formed were calculated using the Klotz equation. Binding site markers dedicated to HSA and AGP were applied to identify high-affinity binding sites. Changes in the tertiary and secondary structures were evaluated using fluorescence; UV-Vis and circular dichroism spectroscopic studies. Isothermal titration nanocalorimetry (nanoITC) was used to determine thermodynamic parameters; which may suggest possible dominant contributions responsible for complex stabilization. The results indicate that Salt4 forms static and predominantly stable complexes with moderate affinity in one class of binding sites with both HSA and AGP. The Salt4-HSA and Salt4-AGP complexation processes are spontaneous and multifactorial; involving hydrophobic interactions; dehydration of the binding site; solvent reorganization; and structural adaptation of the protein; hydrophobic interactions may be the dominant type of bond responsible for the stability of the complexes under study. Salt4 affects the tertiary structure of the studied proteins but does not change their secondary structure. The preliminary results confirm that the adopted research hypothesis is promising and justify further studies.
Keywords:
9-hydroxy-5-methyl-12(H)-quino[3
4-b][1
4]-benzothiazine chloride
circular dichroism spectroscopy
isothermal titration nanocalorimetry
ligand-protein interactions
main plasma carrier proteins
spectrofluorescence
UV-vis spectroscopy
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