Current Drug Targets - Volume 25, Issue 9, 2024

Neglected diseases are a group of infectious diseases, many of them parasitic, that mainly affect the poorest populations with limited access to health services, especially those living in remote rural areas and slums. According to the World Health Organization (WHO), neglected diseases put the lives of more than 200 million people at risk, and treatment is made difficult by the occurrence of resistance to existing medications, as well as the high level of toxicity. In this way, the potential of multitarget compounds is highlighted, defined as compounds designed to modulate multiple targets of relevance to disease, with the overall goal of enhancing efficacy and/or improving safety. Thus, the objective of our study is to evaluate existing multitarget compound approaches for neglected diseases, with an emphasis on Leishmaniasis, Chagas Disease, and Arboviruses. A literature review was performed by searching the database “Web of Sciences”. In relation to the diseases covered in this work, Leishmaniasis, individually, was the one that presented the largest number of articles (11) that dealt with the topic, which can be justified by the high prevalence of this disease in the world, the second most common disease was Dengue, followed by Chagas disease, Chikungunya virus, and Zika virus. Furthermore, the multitarget potential of phenolic compounds was observed in all diseases under study, with the mechanisms related to the nucleus and transcription being the most reported mechanisms. From this perspective, it is worth highlighting the effectiveness of approaches related to multitarget drugs in discovering new therapeutic agents for neglected diseases.

Multi-target drug treatment has become popular as a substitute for traditional monotherapy. Monotherapy can lead to resistance and side effects. Multi-target drug discovery is gaining importance as data on bioactivity becomes more abundant. The design of multi-target drugs is expected to be an important development in the pharmaceutical industry in the near future. This review presents multi-target compounds against trypanosomatid parasites (Trypanosoma cruzi, T. brucei, and Leishmania sp.) and tuberculosis (Mycobacterium tuberculosis), which mainly affect populations in socioeconomically unfavorable conditions. The article analyzes the studies, including their chemical structures, viral strains, and molecular docking studies, when available. The objective of this review is to establish a foundation for designing new multi-target inhibitors for these diseases.

The increasing demand for novel antitubercular agents has been the main 'force' of many TB research efforts due to the uncontrolled growing number of drug-resistant strains of M. tuberculosis in the clinical setting. Many strategies have been employed to address the drug-resistant issue, including a trend that is gaining attention, which is the design and discovery of Mtb inhibitors that are either dual- or multitargeting. The multiple-target design concept is not new in medicinal chemistry. With a growing number of newly discovered Mtb proteins, numerous targets are now available for developing new biochemical/cell-based assays and computer-aided drug design (CADD) protocols. To describe the achievements and overarching picture of this field in anti- infective drug discovery, we provide in this review small molecules that exhibit profound inhibitory activity against the tubercle bacilli and are identified to trace two or more Mtb targets. This review also presents emerging design methodologies for developing new anti-TB agents, particularly tailored to structure-based CADD.

Introduction: Chikungunya fever is a disease caused by infection with the Chikungunya virus, transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Despite its self-limited character, more than 60% of patients have chronic recurrent arthralgia with debilitating pain that lasts for years. Aim: The objective of this review was to gather and analyze evidence from the literature on potential therapeutic strategies with molecules from natural products for the treatment of Chikungunya fever. Methods: A search was performed for clinical trials, observational studies, in vitro or in vivo, without restriction of the year of publication or language in electronic databases (Medline/PubMed, EMBASE, Google Scholar, The Cochrane Library, LILACS (BVS), clinical trial registries (Clinical Trials.gov), digital libraries from CAPES theses and dissertations (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil) and conference abstracts. A quality assessment of the selected studies was performed using the SYRCLE, RoB2 and SciRAP tools. Results: 42 studies were included, which showed molecules with potential antiviral pharmacological activity or with activity in reducing the joint complications caused by CHIKV infection. Conclusions: Among the molecules found in the survey of references, regarding the class of secondary metabolites, flavonoids stood out and for this reason, the molecules may be promising candidates for future clinical trials. Overall, evidence from in vitro studies was of acceptable quality; in vivo and intervention studies showed a high risk of bias, which is a limitation of these studies.