Challenges Based on Antiplasmodial and Antiviral Activities of 7-Chloro-4-aminoquinoline Derivatives

We report the structural functionalization of the terminal amino group of N-1-(7-chloroquinolin-4-yl) butane-1,4-diamine, leading to a series of 7-chloro-4-aminoquinoline derivatives, and their evaluation as potent anti-malarial and anti-viral agents. Some compounds exhibited promising anti-malarial effects against the Plasmodium falciparum 3D7 (chloroquine-sensitive) and Dd2 (chloroquine-resistant) strains. In addition, these compounds were assayed in vitro against influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compound 5 h, bearing an N-mesityl thiourea group, displayed pronounced anti-infectious effects against malaria, IAV, and SARS-CoV-2. These results provide new insights into drug discovery for the prevention or treatment of malaria and virus co-infection.

Automated summary

We have modified the terminal amino group of N-1-(7-chloroquinolin-4-yl) butane-1,4-diamine to synthesize a series of 7-chloro-4-aminoquinoline derivatives and evaluated their potential as anti-malarial and anti-viral agents. Some of these compounds showed promising anti-malarial effects against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. In addition, they were tested in vitro against influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compound 5h, which contained an N-mesityl thiourea group, exhibited significant anti-infectious effects against malaria, IAV, and SARS-CoV-2. These findings provide new insights for the discovery of drugs for malaria prevention and treatment, as well as virus co-infection.