title: Synthesis of Pyrazine-1,3-thiazine Hybrid Analogues as Antiviral Agent Against HIV-1, Influenza A (H1N1), Enterovirus 71 (EV71), and Coxsackievirus B3 (CVB3).
abstract: 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 (EV71); 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 (IC50 3.26 ± 0.2 μm). Moreover, the compound 3d was found to be the most potent analogue to inhibit the H1N1 virus with IC50 of 5.32 ± 0.4 μm together with inhibition of the neuraminidase enzyme (IC50 11.24 ± 1.1 μm). In regard to inhibitory activity against enterovirus 71 (EV71) and coxsackievirus B3 (CVB3), 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.
authors.affiliation: Department of Clinical Laboratory, Liaocheng People's Hospital of Taishan Medical University, Shandong, 252000, China.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, Liaocheng People's Hospital of Taishan Medical University, Shandong, 252000, China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory, Yucheng People's Hospital, Shandong, 251200, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, Liaocheng People's Hospital of Taishan Medical University, Shandong, 252000, China.|Shandong University School of Medicine, Shandong, 250012, China.
authors.forename: Yin-Guang
authors.initials: YG
authors.lastname: Cao
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004285:Dogs; D004770:Enterovirus / Q000187:drug effects; D029821:Enterovirus A, Human / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D061985:Madin Darby Canine Kidney Cells; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D013843:Thiazines
keywords: H1N1; HIV-1; antiviral activity; coxsackievirus B3; enterovirus 71 (EV71); synthesis