Spectrophotometric Studies of the Interaction of Chloroquine with Deoxyribonucleic Acid

Hydroxychloroquine Exhibits a Strong Complex Interaction with DNA: Unraveling the Mechanism of Action

“…Such constant is considerably higher than the result found for the second mode (∼6.25 × 10 4 M –1 from averaging the results found from the persistence and contour length analyses). Cohen et al and Yielding et al have previously reported two binding constants for the interaction of the analog chloroquine (CLQ) with DNA, in agreement with our results. Kwakye-Berko et al report that the equilibrium association constant of DNA–CLQ interaction decreases for high ionic strengths, achieving ∼382 M –1 at 100 mM [Na] .…”

“…Hydroxychloroquine (HCLQ) differs from chloroquine (CLQ) only by a hydroxyl group, a modification that is related to a decrease in the toxicity of the compound. , Irvin et al and Berko et al suggested that the antimalarial effects of chloroquine depend on its interaction with deoxyribonucleic acid (DNA). , However, as already mentioned, although much more studied than HCLQ, the interaction between CLQ and dsDNA is still a controversial subject. While Cohen et al and Berko et al suggested an electrostatic interaction, Irvin et al have found an intercalative behavior, as discussed in the review article by Meshnick . Considering the divergent results presented in the literature and the use of HCLQ for COVID-19 therapy in some countries, it is urgent to comprehend in more detail the mechanism of action of this drug, its selectivity, and its interactions with biomolecules and cells.…”

Endocytosis and chloroquine accumulation during the cell cycle of hepatoma cells in culture.

“…In our opinion, the presence of chloroquine in the high density region, not reported for fibroblasts (40), is a result of the use of the whole homogenate instead of postnuclear supernates. Association with the nucleus could result from interactions (in the intact cell or after homogenization) between chloroquine and DNA (10,24). As in fibroblasts (40), the chloroquine distribution is different from that of lysosomal hydrolases in the low density region.…”

Update Sobre Os Cuidados Paliativos No Contexto Da Covid-19

“…Os efeitos intracelulares das 4-aminoqunolinas são diversos, entre eles: alteração da acidez lisossomal, alteração nas propriedades de apresentação antigênica de fagócitos (SPERBER et al, 1993), inibição da fosfolipase A2 (LÖFFLER et al, 1985), alteração na absorção de raios UV (LESTER et al, 1967), quebra da estabilidade do DNA (COHEN;YIELDING, 1965), inibição da sinalização dos receptores toll-like, inibição receptores de membrana em células T e B que reduz a produção nas células já citadas e também em macrófagos de IL-1, IL-6 e Fator de Necrose Tumoral α (TNF-α) (SPERBER et al, 1993;ZVI et al, 2012). Essas últimas três alterações são suportadas por alguns estudos como a principal forma que a HCQ modula o processo inflamatório (BORNE et al, 1997;SACRE;CRISWELL;LI et al, 2018) com relatos de redução do dano tecidual e endotelial que poderia impedir a evolução de uma reação inflamatória alterada (MOUDGIL; CHOUBEY, 2011).…”