Interaction of VIVO-8-hydroxyquinoline species with RNase A : the effect of metal ligands in the protein adduct stabilization
Ferraro, Giarita (Università degli Studi di Napoli Federico II. Dipartimento di Scienze Chimiche)
Vitale, Luigi (Università degli Studi di Napoli Federico II. Dipartimento di Scienze Chimiche)
Sciortino, Giuseppe (Institut d'Investigacions Químiques de Catalunya)
Pisanu, Federico (Università di Sassari)
Garribba, Eugenio (Università di Sassari. Dipartimento di Medicina, Chirurgia e Farmacia)
Merlino, Antonello (Università degli Studi di Napoli Federico II. Dipartimento di Scienze Chimiche)

Date:	2023
Abstract:	Herein, we studied the interaction of bovine pancreatic ribonuclease (RNase A) with [VIVO(8-HQ)2] - a promising antitrypanosomal, antituberculosis, and antitumor vanadium complex (VC) formed by 8-hydroxyquinolinato (8-HQ), reaching IC50 values lower than cisplatin in HCT116 and A2780 cancer lines (0. 99 and 0. 96 μM vs. 15. 0 and 3. 4 μM) and the minimum inhibitory concentration (MIC) of 3. 7 μM against strains of Mycobacterium tuberculosis. The system was investigated by spectroscopic (UV-vis absorption spectroscopy, circular dichroism, and electron paramagnetic resonance), computational (docking and DFT calculations), and X-ray crystallographic multi-technique approach. Crystallographic results at pH 5. 1 demonstrate that upon interaction with the protein, one of the 8-HQ ligands is replaced by a water molecule and by Glu111 side-chain, resulting in the inhibition of the RNase A activity. EPR data confirm the formation of this adduct, with VIV coordinated by 8-HQ and by the couples (Glu-COO-; H2O) at pH 5. 1, (His-N; H2O) at pH 7. 4, and (His-N; OH-) or (Ser/Thr-O-, H2O) at pH 8. 4. Computational data unveil the reasons behind the ligand exchange, not observed for similar complexes like [VIVO(picolinato)2] and not predicted by thermodynamic considerations. Overall, our results show that the VC-protein binding is defined not only by the thermodynamic stability of VC but also by other factors, such as the structure and steric requirements of the metal ligands, with important implications in the drug delivery strategies.
Grants:	Ministerio de Ciencia e Innovación FJC2019-039135-I
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	SDG 3 - Good Health and Well-being
Published in:	Inorganic Chemistry Frontiers, Vol. 10, Issue 17 (September 2023) , p. 5186-5198, ISSN 2052-1553

DOI: 10.1039/d3qi01023f

13 p, 1.1 MB

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