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Master's Dissertation
DOI
https://doi.org/10.11606/D.76.2024.tde-24042024-100455
Document
Author
Full name
Paulo Nunes de Souza
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Carlos, 2024
Supervisor
Committee
Mascarenhas, Yvonne Primerano (President)
Clavijo, Juan Carlos Tenorio
Júnior, Paulo de Sousa Carvalho
Title in Portuguese
Reposicionamento farmacêutico do fármaco Aciclovir: Novos sais
Keywords in Portuguese
COVID-19
Difração de raios X
Reposicionamento farmacêutico
Sais farmacêuticos
Abstract in Portuguese
Reposicionamento farmacêutico está se tornando uma excelente estratégia em termos de oferecer vantagens sobre o desenvolvimento tradicional de medicamentos, uma vez que a descoberta de fármacos é um processo caro, demorado e altamente arriscado. Com a chegada do coronavírus (COVID-19), declarada pela Organização Mundial da Saúde como uma patologia pandêmica, surgiu uma enorme necessidade de desenvolver agentes terapêuticos capazes de prevenir surtos de vírus. Concomitantemente, drogas conhecidas e usadas há muito tempo, como o aciclovir (ACV), foram testadas contra o COVID-19. ACV é uma droga antiviral análoga de guanosina, comumente usada para tratar o vírus herpes simplex (HSV), herpes genital e vírus varicela zoster (VZV). O testes clínicos realizados oportunamente mostraram que o ACV inibe a proteases virais, expressões genéticas múltiplas virais e RNA-dependente e RNA-polymerase, ajudando assim na recuperação de pacientes com COVID- 19. No entanto, o ACV é uma droga classe III/IV do Sistema de Classificação Biofarmacêutica, apresentando baixa permeabilidade e/ou solubilidade aquosa (dependente da concentração). Dentro deste contexto, neste trabalho são apresentadas quatro novos sais de ACV (um sal nitrato, dois sais brometo e um sal hidrogenosulfato), visando melhorar suas propriedades farmacocinéticas. Os novos sais foram avaliados por difração de raios X, análises térmicas, técnicas espectroscópicas, assim como estudos de solubilidade. O sal cloreto, já reportado na literatura, também foi caracterizado e utilizado para comparação.
Title in English
Drug repurposing of the drug Acyclovir: New salts
Keywords in English
COVID-19
Drug repurposing
Pharmaceutical salts
X-ray diffraction
Abstract in English
Drug repurposing is becoming a good strategy in terms of offering advantages over the traditional drug development, once drug discovery is a costly, time-consuming, and highly risky process. Particularly, with the Coronavirus disease (COVID-19), declared by World Health Organization as pandemic, there emerged a huge need to develop therapeutic agents capable of preventing virus outbreaks. Concomitantly, well known and long used drugs, such as acyclovir (ACV), were allowed to be tested against COVID-19. ACV is a well-known antiviral drug, guanosine analogue, commonly used to treat herpes simplex virus (HSV), genital herpes, and varicella zoster virus (VZV). ACV showed to inhibit viral proteases, multiple viral gene expressions, RNA-dependent and RNA-polymerase, helping toward COVID-19 patients recovery. However, ACV is a BCS class III/IV drug, with low permeability and/or slight water solubility (concentration dependent). Within this framework, in this work three new inorganic salts with this drug are presented (one nitrate, two bromides and one sulfate), aiming to improve its pharmacokinetics properties. The new salts were evaluated by X-ray diffraction, thermal, and spectroscopic analyses. A fifth salt, the chloride one, was also characterized and used for comparison.
 
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Publishing Date
2024-04-24
 
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