β-环糊精和甲基-β-环糊精与萘醌包合物的抗锥虫和抗SARS-CoV-2潜力评估

The evaluation of antichagasic and -SARS-CoV-2 potential of inclusion complexes of β- and methyl-β-cyclodextrin with naphthoquinone.

作者信息

Oliveira Verônica da Silva, Silva Cláudia Cândida, de Freitas Oliveira Johny Wysllas, da Silva Marcelo de Sousa, Ferreira Patricia Garcia, da Siva Fernando de Carvalho, Ferreira Vitor Francisco, Barbosa Euzébio Guimarães, Barbosa Cecília Gomes, Moraes Carolina Borsoi, Freitas-Junior Lucio Holanda Gondim de, Converti Attilio, Lima Ádley Antonini Neves de

机构信息

Department of Pharmacy, Health Sciences Center, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012-570, Brazil.

School of Technology, State University of Amazonas, Manaus, Amazonas, 69065-020, Brazil.

出版信息

J Drug Deliv Sci Technol. 2023 Mar;81:104229. doi: 10.1016/j.jddst.2023.104229. Epub 2023 Feb 8.

DOI:10.1016/j.jddst.2023.104229

PMID:36776572

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9905044/

Abstract

The compound 3,10-dihydro-1-cyclopenta[]naphtho[2,3-]furan-5,10-dione (IVS320) is a naphthoquinone with antifungal and antichagasic potential, which however has low aqueous solubility. To increase bioavailability, inclusion complexes with β-cyclodextrin (βCD) and methyl-β-cyclodextrin (MβCD) were prepared by physical mixture (PM), kneading (KN) and rotary evaporation (RE), and their -SARS-CoV-2 and antichagasic potential was assessed. The formation of inclusion complexes led to a change in the physicochemical characteristics compared to IVS320 alone as well as a decrease in crystallinity degree that reached 74.44% for the IVS320-MβCD one prepared by RE. The IVS320 and IVS320-MβCD/RE system exhibited -SARS-CoV-2 activity, showing half maximal effective concentrations (EC) of 0.47 and 1.22 μg/mL, respectively. Molecular docking simulation suggested IVS320 ability to interact with the SARS-CoV-2 viral protein. Finally, the highest antichagasic activity, expressed as percentage of growth inhibition, was observed with IVS320-βCD/KN (70%) and IVS320-MβCD/PM (72%), while IVS320 alone exhibited only approximately 48% inhibition at the highest concentration (100 μg/mL).

摘要

化合物3,10 - 二氢 - 1 - 环戊[a]萘并[2,3 - b]呋喃 - 5,10 - 二酮（IVS320）是一种具有抗真菌和抗恰加斯病潜力的萘醌，但水溶性较低。为提高生物利用度，通过物理混合（PM）、捏合（KN）和旋转蒸发（RE）制备了与β - 环糊精（βCD）和甲基 - β - 环糊精（MβCD）的包合物，并评估了它们的抗SARS-CoV-2和抗恰加斯病潜力。与单独的IVS320相比，包合物的形成导致了物理化学特性的变化以及结晶度的降低，通过RE制备的IVS320 - MβCD包合物的结晶度降低至74.44%。IVS320和IVS320 - MβCD/RE体系表现出抗SARS-CoV-2活性，半数最大有效浓度（EC）分别为0.47和1.22μg/mL。分子对接模拟表明IVS320能够与SARS-CoV-2病毒蛋白相互作用。最后，观察到IVS320 - βCD/KN（70%）和IVS3-C20 - MβCD/PM（72%）具有最高的抗恰加斯病活性，以生长抑制百分比表示，而单独的IVS320在最高浓度（100μg/mL）时仅表现出约48%的抑制作用。