From hybrid compounds to targeted drug delivery in antimalarial therapy

Oliveira, Rudi; Miranda, Daniela; Magalhães, Joana; Capela, Rúben A.; Perry, Maria de Jesus; Moreira, Rui; Lopes, Francisca

doi:10.1016/j.bmc.2015.04.017

Cited by 39 publications

(15 citation statements)

References 71 publications

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“…In this study, we employed one of the classical medicinal chemists’ tools—the combination of two pharmacophores in one molecule . The concept of hybrid drugs is also a valuable strategy to overcome the limitations of a combined therapy, as the resulting molecules could exhibit inhibitory activities on multiple targets .…”

Section: Introductionmentioning

confidence: 99%

“…[49,50] In this study,w ee mployed one of the classical medicinal chemists' tools-the combination of two pharmacophores in one molecule. [7,[51][52][53][54] The concept of hybridd rugs is also av aluable strategy to overcome the limitations of ac ombined therapy,a st he resulting molecules could exhibit inhibitory activities on multiple targets. [55] The hybridc ompounds described here, SAHAquines, combine motifs of SAHA, an anticancer agent with weak antiplasmodial activity,a nd PQ, an antimalarial drug with low antiproliferative activity.…”

Section: Introductionmentioning

confidence: 99%

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SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

et al. 2018

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We report the synthesis of SAHAquines and related primaquine (PQ) derivatives. SAHAquines are novel hybrid compounds that combine moieties of suberoylanilide hydroxamic acid (SAHA), an anticancer agent with weak antiplasmodial activity, and PQ, an antimalarial drug with low antiproliferative activity. The preparation of SAHAquines is simple, cheap, and high yielding. It includes the following steps: coupling reaction between primaquine and a dicarboxylic acid monoester, hydrolysis, a new coupling reaction with O‐protected hydroxylamine, and deprotection. SAHAquines 5 a–d showed significant reduction in cell viability. Among the three human cancer cell lines (U2OS, HepG2, and MCF‐7), the most responsive were the MCF‐7 cells. The antibodies against acetylated histone H3K9/H3K14 in MCF‐7 cells revealed a significant enhancement following treatment with N‐hydroxy‐N′‐{4‐[(6‐methoxyquinolin‐8‐yl)amino]pentyl}pentanediamide (5 b). Ethyl (2E)‐3‐({4‐[(6‐methoxyquinolin‐8‐yl)amino]pentyl}carbamoyl)prop‐2‐enoate (2 b) and SAHAquines were the most active compounds against both the hepatic and erythrocytic stages of Plasmodium parasites, some of them at sub‐micromolar concentrations. The results of our research suggest that SAHAquines are promising leads for new anticancer and antimalarial agents.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

et al. 2018

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“…Many hybrid molecules are under clinical evaluations for the treatment of various diseases including those caused by drug‐resistant organisms, so hybridization represents a promising strategy to develop new drugs . Hybridization of quinoline moiety with other antimalarial pharmacophores is prone to provide novel antimalarial candidates with high in vitro and in vivo potency against drug‐resistant P falciparum . There are four major types of quinoline hybrids reported during the last 10 years: Type I quinoline‐artemisinin (or its derivatives), Type II quinoline‐synthetic peroxide, Type III quinoline‐resistance reverse agents, and Type IV quinoline‐novel antimalarial pharmacophores (Figure ) …”

Section: Introductionmentioning

confidence: 99%

Hybrid molecules with potential in vitro antiplasmodial and in vivo antimalarial activity against drug‐resistant Plasmodium falciparum

Feng

Chang

et al. 2019

Medicinal Research Reviews

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Malaria is a tropical disease, leading to around half a million deaths annually. Antimalarials such as quinolines are crucial to fight against malaria, but malaria control is extremely challenged by the limited pipeline of effective pharmaceuticals against drug-resistant strains of Plasmodium falciparum which are resistant toward almost all currently accessible antimalarials. To tackle the growing resistance, new antimalarial drugs are needed urgently. Hybrid molecules which contain two or more pharmacophores have the potential to overcome the drug resistance, and hybridization of quinoline privileged antimalarial building block with other antimalarial pharmacophores may provide novel molecules with enhanced in vitro and in vivo activity against drug-resistant (including multidrug-resistant) P falciparum. In recent years, numerous of quinoline hybrids were developed, and their activities against a panel of drug-resistant P falciparum strains were screened. Some of quinoline hybrids were found to possess promising in vitro and in vivo potency. This review emphasized quinoline hybrid molecules with

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“…Plasmodium falciparum , the causative agent of the most malignant forms of malaria is particularly a resistant parasite, which is identified to have high adaptability as a result of mutation. This mutability makes it quite probable for the development of resistance to current chemotherapeutic regime . In the context, it was thought worth to develop hybrid molecules containing different pharmacophoric entities in single molecular frame work owing varied pharmacological properties.…”

Section: Introductionmentioning

confidence: 99%

Microwave‐Assisted Synthesis of Novel Pyrazole Clubbed Polyhydroquinolines in an Ionic‐Liquid and their Biological Perspective

et al. 2018

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A series of diarylpyrazole clubbed polyhydroquinoline derivatives (6a‐j, 7a‐j, 8a‐j) were synthesized by one pot multicomponent methodology using ionic liquid (Bbpy)(HSO4)2 as solvent as well as catalyst under microwave irradiation as energy source. The synthesized entities were further screened in vitro for their preliminary biocidal potency against group of pathogenic bacterial as well as fungal strains; against M. tuberculosis H37Rv strain for antituberculosis activity and against P. falciparum to evaluate antimalarial potency. A number of compounds were found to render antibacterial activity against bacterial strains as compared to standard drugs. Compounds 6b, 6 f, 8e and 8j were found to possess higher antibacterial potency as compared to ampicillin as well as comparable to ciprofloxacin and chloramphenicol. The compounds 6e, 6j, 7e, 7j and 8j (MIC: 100 μg/mL) were found to be highly potent as antifungal candidates against C. albicans as compared to griseofulvin. For antituberculosis activity, compounds 8e, 8 h and 8j were found to be potent candidates against M. tuberculosis H37Rv strain as compared to rifampicin. Compounds 7a, 7c, 7d, 7 f, 7 h, 8d and 8i were found to be highly potent as compared to quinine (0.268 μg/mL) and comparable activity as to chloroquine (0.020 μg/mL). The cytotoxicity of the synthesized compounds was evaluated against Vero cell proving their non‐toxic behavior.

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From hybrid compounds to targeted drug delivery in antimalarial therapy

Cited by 39 publications

References 71 publications

SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

Hybrid molecules with potential in vitro antiplasmodial and in vivo antimalarial activity against drug‐resistant Plasmodium falciparum

Microwave‐Assisted Synthesis of Novel Pyrazole Clubbed Polyhydroquinolines in an Ionic‐Liquid and their Biological Perspective

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