Design, synthesis and structure-activity relationship of dihydrobenzoquinolines as novel inhibitors against influenza A virus

• Published in: European journal of medicinal chemistry 2022-12, Vol.244, p.114799-114799, Article 114799
• Main Authors: Liao, Hui, Li, Yinyan, Yu, Luqiang, Wu, Zemin, Yang, Jie, Zhu, Qiuhua
• Format: Article
• Language: English
• Subjects: Design and synthesis; Dihydrobenzoquinolines; Influenza A virus; Multicomponent reaction; Structure-activity relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2022.114799

Novel dihydrobenzo[h]quinolines (DHBQs), the products of an efficient catalyst-free three-component reaction (3CR) recently developed by us, possess useful and strong aggregation-induced emission (AIE) characteristic. Here, a series of new dihydrobenzo[h]quinolines (h-DHBQs 4–1−34) and dihydrobenzo[f]quinolines (f-DHBQs 5a−e) were designed and synthesized by the 3CR to study their bioactivities as novel inhibitors against the influenza A (H1N1) virus. The structure-activity relationship (SAR) indicates that the antiviral activities of DHBQs depend on the combination of substituents and three of h-DHBQs (4–12, 4–25 and 4–27) show potent antiviral activity with IC50 = 2.52–3.79 μM. These potent h-DHBQs have low toxicity to MDCK and A549 cells (CC50 > 100 μM for 4–12 and > 50/100 μM for 4–25 and 4–27). The primary mechanism of the antiviral activities of DHBQs was studied using the most potent h-DHBQ 4–12, which indicated that 4–12 could efficiently inhibit virus-induced plaque formation and NP/PB2 protein expression in a dose-dependent way. DHBQs with simple synthetic method, useful AIE characteristic and antiviral activities are expected to be developed into potential inhibitors against influenza A virus, at the same time acting as chemical/biological fluorescent probe. [Display omitted] •39 DHBQs have been designed and synthesized by a three-component reaction.•The antiviral activities of DHBQs depend on the combination of substituents.•Three of h-DHBQs show potent inhibition effects on the influenza A (H1N1) virus.•h-DHBQ 4–12 dose-dependently inhibits the expressions of NP and PB2 proteins.