1621164-56-4Relevant academic research and scientific papers
Docking of anti-HIV-1 oxoquinoline-acylhydrazone derivatives as potential HSV-1 DNA polymerase inhibitors
Yoneda, Julliane Diniz,Albuquerque, Magaly Gir?o,Leal, Kátia Zaccur,Santos, Fernanda Da Costa,Batalha, Pedro Netto,Brozeguini, Leonardo,Seidl, Peter R.,De Alencastro, Ricardo Bicca,Cunha, Anna Cláudia,De Souza, Maria Cecília B.V.,Ferreira, Vitor F.,Giongo, Viveca A.,Cirne-Santos, Cláudio,Paix?o, Izabel C.P.
, p. 263 - 270 (2014)
Although there are many antiviral drugs available for the treatment of herpes simplex virus (HSV) infections, still the synthesis of new anti-HSV candidates is an important strategy to be pursued, due to the emergency of resistant HSV strains mainly in human immunodeficiency virus (HIV) co-infected patients. Some 1,4-dihydro-4-oxoquinolines, such as PNU-183792 (1), show a broad spectrum antiviral activity against human herpes viruses, inhibiting the viral DNA polymerase (POL) without affecting the human POLs. Thus, on an ongoing antiviral research project, our group has synthesized ribonucleosides containing the 1,4-dihydro-4-oxoquinoline (quinolone) heterocyclic moiety, such as the 6-Cl derivative (2), which is a dual antiviral agent (HSV-1 and HIV-1). Molecular dynamics simulations of the complexes of 1 and 2 with the HSV-1 POL suggest that structural modifications of 2 should increase its experimental anti-HSV-1 activity, since its ribosyl and carboxyl groups are highly hydrophilic to interact with a hydrophobic pocket of this enzyme. Therefore, in this work, comparative molecular docking simulations of 1 and three new synthesized oxoquinoline-acylhydrazone HIV-1 inhibitors (3-5), which do not contain those hydrophilic groups, were carried out, in order to access these modifications in the proposition of new potential anti-HSV-1 agents, but maintaining the anti-HIV-1 activity. Among the docked compounds, the oxoquinoline-acylhydrazone 3 is the best candidate for an anti-HSV-1 agent, and, in addition, it showed anti-HIV-1 activity (EC50 = 3.4 ± 0.3 μM). Compounds 2 and 3 were used as templates in the design of four new oxoquinoline-acylhydrazones (6-9) as potential anti-HSV-1 agents to increase the antiviral activity of 2. Among the docked compounds, oxoquinoline-acylhydrazone 7 was selected as the best candidate for further development of dual anti-HIV/HSV activity.
Effects of novel acylhydrazones derived from 4-quinolone on the acetylcholinesterase activity and Aβ42 peptide fibrils formation
da Silva, Gisele S.,Figueiró, Micheli,Tormena, Claudio F.,Coelho, Fernando,Almeida, Wanda P
, p. 1464 - 1470 (2016/10/09)
Acetylcholinesterase inhibitors and compounds that trigger Aβ amyloid oligomerization and fibrillization represent an opportunity to discover new drug candidates to treat Alzheimer’s disease. In this work, we synthesized nine new acylhydrazones and a known one, both employing 3-carboethoxy-4-quinolone derivatives as starting materials with chemical yields ranging from 63% to 90%. We evaluated the effect of these compounds on the acetylcholinesterase (AChE) activity and the fibrillization of Aβ42 peptide. Except for one acylhydrazone, the compounds exhibited good inhibitory effect on AChE (1.2 μM 50 values a significant decrease in the thioflavin-T fluorescence emission, suggesting an inhibitory effect on the Aβ42 fibril formation.
