Abstract
The molecular hybridization approach has been used to develop compounds with improved efficacy by combining two or more pharmacophores of bioactive scaffolds. In this context, hybridization of various relevant pharmacophores with phenothiazine derivatives has resulted in pertinent compounds with diverse biological activities, interacting with specific or multiple targets. In fact, the development of new drugs or drug candidates based on phenothiazine system has been a promising approach due to the diverse activities associated with this tricyclic system, traditionally present in compounds with antipsychotic, antihistaminic and antimuscarinic effects. Actually, the pharmacological actions of phenothiazine hybrids include promising antibacterial, antifungal, anticancer, anti-inflammatory, antimalarial, analgesic and multi-drug resistance reversal properties. The present review summarizes the progress in the development of phenothiazine hybrids and their biological activity.
Highlights
In complex diseases there are many factors at play, such as genetic, lifestyle, and environmental factors that interact and lead to an observed phenotype [1]
As multiple factors are involved in these diseases, its cure or effective treatment frequently depends on achieving multiple targets and the use of a single drug with a single target may not be appropriate [3]
Therapies with single drugs are available for some diseases, their efficacy can decrease due to several reasons, such as multidrug resistance [4]
Summary
In complex diseases there are many factors at play, such as genetic, lifestyle, and environmental factors that interact and lead to an observed phenotype [1]. The use of combined therapeutic approaches has been highlighted due to its ability to act on multiple targets and as a strategy to overpass the reduction of drug efficacy This is based on the concomitant use of at least two different bioactive molecules with complementary pharmacological activity and different modes of action, which in turn can lead to enhanced therapeutic effects by different pathways, namely as a result of synergism [3]. Molecules 2022, 27, 276 molecular hybridization is based on coupling two or more pharmacophores, haptop2hoof r3e2s or entire drugs with different biological functions in one molecule using or not a linker chain [6] These compounds should have additive or, preferentially, synergistic effects wwhhilielebbeeaarirninggththeeeexxppeectceteddpphhaarmrmaacocolologgiciacal lpprorofiflielsesfofor rclcilniniciaclaluusese[7[7].].HHyybbrirdidmmooleleccuuleless ccaannaalslsoommininimimizizeeththeerirsikskoof fddrurugg-d-druruggininteteraractcitoionnssaannddththeeppootetenntitaial lddeevveeloloppmmeennttooff ddruruggrerseissitsatnancec.eI.nInadadidtiotino,nt,htihsirsartaiotinoanladlrdurgudgedsiegsnigsntrsattreagtyegcyancaanlloawllofworfaoreadruecdtiuocntiionn dionsdagoesaagsewaesllwaesllinasadinveardsveedrsreugdrueagcrtieoancsti.oSnusc.cSeusscfcuelslsyfumllayrkmeaterdkedterudgdhruybgrhidysb(rriedlsev(raenlet evxanmtpelxeasminpleFsiginurFeig1u)rien1c)luindcel,udame,oanmgonogthoetrhse, rzsi,pzriapsriadsoidnoen(ea(natniptispyscyoctohtihci)c, )d, duuloloxxeetitninee (a(anntitdideepprersesasannt)t,),aannddlalpapataitninibib(u(usesdedtototrteraetatbrberaesatsct acnacnecrerovoevreerxepxrpersessisnigngErEbrBb2B)2[)4[]4.]. Tohleecruefloarre,htyhbirsisdciazfaftoioldn. hTahs ebreeefnorsee,letchtiesdsfcoarffhoylbdrihdaizsatbieoennwsiethleocttehder fmorolhecyublreisdtizoasttiroenngwthitehn tohteheerffemctoivleecnuelsessotfo thsteremnugltthiteanrgtehteaepfpfercotaivchenesesosrotof tohbetaminuolttihtaerrgpeot taepnptiraollaychreelsevoarntot boibotaacitnivoittiheesr[4p]o. tentially relevant bioactivities [4]
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