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Synthesis of Pyrazine‐1,3‐thiazine Hybrid Analogues as Antiviral Agent Against HIV ‐1, Influenza A (H1N1), Enterovirus 71 ( EV 71), and Coxsackievirus B3 ( CVB 3)
Author(s) -
Wu HongMin,
Zhou Kuo,
Wu Tao,
Cao YinGuang
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12769
Subject(s) - neuraminidase , coxsackievirus , virology , neuraminidase inhibitor , virus , chemistry , influenza a virus , enzyme , enterovirus , entry inhibitor , microbiology and biotechnology , biology , viral entry , viral replication , biochemistry , medicine , covid-19 , disease , pathology , infectious disease (medical specialty)
A novel series of pyrazine‐1,3‐thiazine hybrid conjugates were synthesized in excellent yield. These derivatives were subsequently tested against human immunodeficiency virus ( HIV ‐1); hemagglutinin type 1 and neuraminidase type 1—'influenza' A (H1N1) virus; enterovirus 71 ( EV 71); and coxsackievirus B3. The effect of these conjugates on the key enzymes responsible for the progression of these viral infections was also illustrated via enzyme‐based assay, such as HIV ‐1 reverse transcriptase ( RT ) and neuraminidase, where entire tested molecules showed considerable inhibition. Particularly, among the tested derivatives, compound 3k was identified as most promising inhibitor of HIV ‐1 with 94% of inhibition ( IC 50 3.26 ± 0.2 μ m ). Moreover, the compound 3d was found to be the most potent analogue to inhibit the H1N1 virus with IC 50 of 5.32 ± 0.4 μ m together with inhibition of the neuraminidase enzyme ( IC 50 11.24 ± 1.1 μ m ). In regard to inhibitory activity against enterovirus 71 ( EV 71) and coxsackievirus B3 ( CVB 3), the tested derivatives showed considerable inhibition of infection. Molecular docking studies were also performed for the most promising inhibitors with their corresponding target protein to exemplify the structural requirement for better inhibitory activity. The results of inhibitory assay showed that designed molecules possess considerable inhibitory activity against the virus tested.