Hybrid Compounds as Direct Multitarget Ligands: A Review
Michelle Oliveira Pedrosa, Rayssa Marques Duarte da Cruz, Jéssika de Oliveira Viana, Ricardo Olímpio de Moura, Hamilton Mitsugu Ishiki, José Maria Barbosa‐Filho, Margareth de Fátima Formiga Melo Diniz, Luciana Scotti, Luciana Scotti, Francisco Bezerra Mendonca · Current Topics in Medicinal Chemistry · 2016
Molecular Hybridization is an approach in rational drug design where new chemical entities are obtained by combining two or more pharmacophoric units from different bioactive compounds into a single molecule. Through this approach, medicinal chemists hope that the new hybrid derivative presents: better affinity and efficacy when compared to the parent drugs; a modified selectivity profile with improvement over pharmacokinetic and pharmacodynamic restrictions; dual or multiple modes of action; reduction of undesirable side effects; decreases in drug-drug interactions; reduced emergence or spread of drug resistance in microorganisms and protozoans; and lower cost. The approach has been successfully used by many research groups around the world and has had very promising results with diseases having multifactorial profiles, like Alzheimer´s, Parkinson´s disease, cancer, inflammation, and hypertension among others. The purpose of this paper is to conduct an updated review of molecular hybridization and multitarget profiling (a rational drug design approach), and its applications to the design and discovery of novel hybrid compounds with anti-inflammatory, antimicrobial, anticancer and antiprotozoal (leishmaniasis, malaria, and schistosomiasis) activities over the last six years.