Computer-Aided Drug Design Using Sesquiterpene Lactones as Sources of New Structures with Potential Activity against Infectious Neglected Diseases

Abstract

This review presents an survey to the biological importance of sesquiterpene lactones (SLs) in the fight against four infectious neglected tropical diseases (NTDs)—leishmaniasis, schistosomiasis, Chagas disease, and sleeping sickness—as alternatives to the current chemotherapies that display several problems such as low effectiveness, resistance, and high toxicity. Several studies have demonstrated the great potential of some SLs as therapeutic agents for these NTDs and the relationship between the protozoal activities with their chemical structure. Recently, Computer-Aided Drug Design (CADD) studies have helped increase the knowledge of SLs regarding their mechanisms, the discovery of new lead molecules, the identification of pharmacophore groups and increase the biological activity by employing in silico tools such as molecular docking, virtual screening and Quantitative-Structure Activity Relationship (QSAR) studies.

Treatment of Leishmania (Leishmania) Amazonensis-Infected Mice with a Combination of a Palladacycle Complex and Heat-Killed Propionibacterium acnes Triggers Protective Cellular Immune Responses

“…Although oral administration of sitamaquine has shown efficacy in the treatment of visceral leishmaniasis, the drug induces undesirable adverse effects (Jha et al, 2005). Therefore, the development of new leishmanicidal drugs continues to be a priority for the control of leishmaniasis and several compounds including synthetic and natural products extracted from plants and marine sources have exhibited different degrees of efficacy in the treatment of experimental leishmaniasis (Sen and Chatterjee, 2011; Tempone et al, 2011; Coa et al, 2015; Ortiz et al, 2016; Acevedo et al, 2017). …”

Efflux pumps and antimicrobial resistance: Paradoxical components in systems genomics

“…Melarsoprol used against Trypanosoma brucei may be lethal in chronic cases. In the past decade, there has been a sudden increase in the cases of resistance of Schistosoma to praziquantel (Acevedo et al, 2017). Peptides like magainin for Paramecium caudatum and cathelicidin for Caenorhabditis elegans have been designed (Bahar and Ren, 2013).…”

Sesquiterpenes evaluation on Schistosoma mansoni : Survival, excretory system and membrane integrity

“…This fact highlights the importance to research new treatment alternatives. In the last few years, some natural compounds isolated from the Terpenes group, have already shown schistosomicidal activity and against others infectious neglected tropical diseases (NTDs) Eg: the monoterpenes, carvacryl acetate, dihydro citronellol and sesquiterpene lactones [5][6][7].…”