Lactobionic Acid as a Biocompatibility Switch: Physicochemical and Biological Characterization of Copper(II)–Primaquine Complexes

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Metal dyshomeostasis and oxidative stress are implicated in the progression of cancer, and neurodegenerative and peripheral aggregation-related disorders. In this study, we investigated primaquine (PQ), a clinically used antimalarial drug, and PQ-lactobionic acid conjugate (LAPQ), a newly synthesized and characterized derivative obtained through conjugation with lactobionic acid, designed to improve physicochemical and biological properties. Both compounds were evaluated for their copper-coordination ability, antioxidant properties, interaction with amyloid-β (Aβ), and capacity to modulate reactive oxygen species (ROS)-induced cellular damage. As a complementary biological line of investigation, their in vitro antiproliferative activity in the presence and absence of copper was also evaluated. The compounds directly interact with Aβ as demonstrated by surface plasmon resonance (SPR) studies. Biological studies revealed marked differences between the two molecules. PQ displayed intrinsic cytotoxicity, whereas LAPQ exhibited enhanced aqueous solubility and substantially reduced antiproliferative activity under the tested conditions, highlighting the impact of sugar conjugation. In cellular oxidative stress models, LAPQ showed a protective effect, preserving cell viability under ROS-generating conditions. In summary, by interacting with Aβ and exhibiting antioxidant activity, two properties relevant to several neurodegenerative and peripheral aggregation-related disorders, our novel compound LAPQ may provide a potential starting point for the development of therapies targeting Aβ-associated disorders.

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