Síntese e avaliação de chalconas O-preniladas contra os vírus Oropouche e Mayaro.
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Data
2021-10-25
Autores
Lemos, Rodrigo Raposo de
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Universidade Estadual Paulista (Unesp)
Resumo
Os vírus Oropouche (OROV) e Mayaro (MAYV) são vírus envelopados causadores da febre oropouche e mayaro, respectivamente. Ambas as infecções podem ser consideradas como zoonoses emergentes e possuem sintomas semelhantes a outras arboviroses, o que dificulta o diagnóstico clínico, causando uma consequente ampla subnotificação nos países da América Latina e Caribe. Não existem vacinas e fármacos disponíveis para a profilaxia e tratamento das infecções por OROV e MAYV. Dessa forma, torna-se necessária a busca e o desenvolvimento de novas substâncias, capazes de interromper o ciclo replicativo desses vírus. Nesse contexto, chalconas podem ser um grupo químico de partida promissor para essa investigação, uma vez que apresentam atividade antiviral contra vários vírus, incluindo o vírus da dengue (DENV), vírus da imunodeficiência humana tipo I (HIV-1), vírus do mosaico do tabaco (TMV) e citomegalovírus (CMV). Nesse presente trabalho foram sintetizadas dez chalconas O-preniladas por meio de duas etapas; (i) reação de O-prenilação do seringaldeído e (ii) reação de Claisen-Schmidt entre os seringaldeído O-prenilado e respectivas acetofenonas. Os rendimentos globais dessas reações variaram de 3% a 17%. As substâncias foram purificadas utilizando cromatografia em coluna de fase normal e de permeação em gel. As estruturas das substâncias foram confirmadas por meio da análise dos espectros de Ressonância Magnética Nuclear de Hidrogênio. Os procedimentos químicos permitiram a obtenção dos produtos isolados em quantidades e pureza adequadas aos ensaios de toxicidade contra células Vero E6 e antiviral. Sete chalconas O-preniladas demonstraram toxicidade contra células Vero E6 na maioria das concentrações testadas e ausente ou fraca inibição da replicação de OROV e MAYV. A chalcona 17, substituída por um grupo amina na posição 2’ do anel A colaborou com uma viabilidade celular em 50% das células Vero E6 infectadas por OROV a 4,7 μM e 9,4 μM.
Oropouche (OROV) and Mayaro (MAYV) are enveloped virus, which are able to cause Oropouche and Mayaro fevers, respectively. Both infections are emergent zoonosis and possess similar symptoms to other arbovirosis, avoiding their clinical diagnosis and subnotifications in Latin America and Caribbean countries. There are not vaccines and drugs to prophylaxis and treatment of OROV and MAYV infections. Thus, the search and development of new compounds is necessary, which are able to finish the replicative cycle of these virus. In this context, chalcones can be starting and promising chemical group to this investigation, considering their antiviral activity against other viruses, including DENV, HIV- 1, TMV and CMV. In this current work, 10 O-prenylated chalcones were synthesized in two steps; (i) O-prenylation reaction of syringaldehyde and (ii) Claisen-Schmidt reaction between O-prenylated syringaldehyde and respective acetophenones. Global yields of these reactions ranged from 3% to 17%. Compounds were purified by chromatographic column separations over normal and gel permeation phases. Structure of compounds were confirmed by Nuclear Magnetic Resonance spectral analyses. Chemical procedures led to isolated products in adequate amounts and purity to toxicity assays against vero E6 cells and antiviral assays. Seven O-prenylated chalcones demonstrated toxicity against Vero E6 cells in tested concentrations and absence or weak inhibition of OROV and MAYV replication. Chalcone 17, which is substituted by amino group at position 2’ on ring A, exhibted 50% cell viability of vero E6 cells infected by OROV at 4.7 µM and 9.4 µM.
Oropouche (OROV) and Mayaro (MAYV) are enveloped virus, which are able to cause Oropouche and Mayaro fevers, respectively. Both infections are emergent zoonosis and possess similar symptoms to other arbovirosis, avoiding their clinical diagnosis and subnotifications in Latin America and Caribbean countries. There are not vaccines and drugs to prophylaxis and treatment of OROV and MAYV infections. Thus, the search and development of new compounds is necessary, which are able to finish the replicative cycle of these virus. In this context, chalcones can be starting and promising chemical group to this investigation, considering their antiviral activity against other viruses, including DENV, HIV- 1, TMV and CMV. In this current work, 10 O-prenylated chalcones were synthesized in two steps; (i) O-prenylation reaction of syringaldehyde and (ii) Claisen-Schmidt reaction between O-prenylated syringaldehyde and respective acetophenones. Global yields of these reactions ranged from 3% to 17%. Compounds were purified by chromatographic column separations over normal and gel permeation phases. Structure of compounds were confirmed by Nuclear Magnetic Resonance spectral analyses. Chemical procedures led to isolated products in adequate amounts and purity to toxicity assays against vero E6 cells and antiviral assays. Seven O-prenylated chalcones demonstrated toxicity against Vero E6 cells in tested concentrations and absence or weak inhibition of OROV and MAYV replication. Chalcone 17, which is substituted by amino group at position 2’ on ring A, exhibted 50% cell viability of vero E6 cells infected by OROV at 4.7 µM and 9.4 µM.
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Vírus Oropouche, Vírus Mayaro, Antivirais, Arboviroses, Chalcone, Arbovirosis, Oropouche virus, Mayaro virus, Antiviral,