RESUMO

A possible inhibitor of proteases, which contains an indole core and an aromatic polar acetylene, was designed and synthesized. This indole derivative has a molecular architecture kindred to biologically relevant species and was obtained through five synthetic steps with an overall yield of 37% from the 2,2'-(phenylazanediyl)di(ethan-1-ol). The indole derivative was evaluated through docking assays using the main protease (SARS-CoV-2-Mpro) as a molecular target, which plays a key role in the replication process of this virus. Additionally, the indole derivative was evaluated as an inhibitor of the enzyme kallikrein 5 (KLK5), which is a serine protease that can be considered as an anticancer drug target.

Assuntos

Acetileno/química , Antivirais/química , Antivirais/síntese química , Indóis/química , Inibidores de Proteases/química , Inibidores de Proteases/síntese química , SARS-CoV-2/enzimologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antivirais/farmacologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Descoberta de Drogas , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Calicreínas/antagonistas & inibidores , Modelos Moleculares , Simulação de Acoplamento Molecular , Inibidores de Proteases/farmacologia , SARS-CoV-2/efeitos dos fármacos , Tratamento Farmacológico da COVID-19

RESUMO

Excellent quadratic non-linear optical (ONL-2) properties of the poly(2,5-bis(but-2-ynyloxy) benzoate, containing a polar diacetylene as a chromophore, were found. According with the Maker fringes method, oriented polymer films showing an order parameter of ∼0.23 can display outstanding and stable Second Harmonic Generation (SHG) effects under off-resonant conditions (SHG-532 nm). Also, the macroscopic non-linear optical (NLO)-coefficients were evaluated under the rod-like molecular approximation, obtaining: χzzz(2) and χzxx(2) in the order of 280 ± 10 and 100 ± 10 pm V-1, respectively. The mechanical and chemical properties, in addition to the large ONL-2 coefficients exhibited by this polymer, make it a promising organic material in the development of optoelectronic/photonic devices.