Introduction

Arthropod-borne viruses (arboviruses) constitute a major group of emerging and re-emerging pathogens transmitted primarily by mosquitoes of the Aedes and Culex genera [1]. These viruses are widely distributed in tropical and subtropical regions and have become an increasing global public health concern due to their expanding geographic range and rising incidence [2]. Among them, dengue virus (DENV), Zika virus (ZIKV), chikungunya virus (CHIKV), and Mayaro virus (MAYV) are of particular relevance, as they are responsible for large outbreaks associated with fever, rash, and severe musculoskeletal symptoms, often leading to long-term morbidity [3–5].

Despite their clinical and epidemiological importance, there are currently no specific antiviral therapies approved for most arboviral infections, and treatment remains largely supportive [6–8]. The continued emergence and co-circulation of these viruses highlight the urgent need to identify and develop novel antiviral agents with improved efficacy and safety profiles. In this context, small synthetic molecules have played a central role in drug discovery, offering structural diversity and opportunities for rational optimization [6–8].

Quinoline and its derivatives represent a privileged scaffold in medicinal chemistry, exhibiting a broad spectrum of biological activities, including well documented antiviral effects [9]. Structural modifications of the quinoline core have led to compounds with activity against several RNA viruses, supporting their potential as templates for the development of new antiviral agents. In particular, 4-aminoquinoline derivatives have attracted attention due to their pharmacological versatility and favorable drug like properties.

In the present study, we report the synthesis and in vitro evaluation of novel 4-amino-7-chloroquinoline derivatives against CHIKV, ZIKV, and MAYV. Furthermore, mechanistic insights into the antiviral activity of the most active compound were investigated through cytopathic effect inhibition assays, virucidal assays, and viral load quantification by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). This work aims to identify promising lead compounds and contribute to the development of new therapeutic strategies against medically relevant arboviruses.