Repositioning Salirasib as a new antimalarial agent

Porta, Exequiel O. J.; Verdaguer, Ignasi Bofill; Perez, Consuelo; Banchio, Claudia; Azevedo, Mauro Ferreira de; Katzin, Alejandro M.; Labadié, Guillermo R.

doi:10.1039/c9md00298g

Cited by 19 publications

(11 citation statements)

References 33 publications

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“…Therefore, special concern should be devoted to the development of new antimicrobial agents, possessing completely different chemical structures, and working with different modes of actions. The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction offers a versatile synthetic access to the 1,2,3-triazole heterocycle derivatives, which are associated with a wide spectrum of pharmacological activities, including antimycobacterial [18][19][20][21], antitubercular [22][23][24][25], anticancer [26][27][28][29], antiviral [30][31][32][33][34], antidiabetic [35][36][37][38], antifungal [39][40][41][42], anti-HIV [43][44][45][46], anti-inflammatory [47][48][49][50], antimalarial [51][52][53][54], anti-oxidant [55][56][57][58], anti-proliferative [59][60][61][62] properties. The 1...…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Antimicrobial Activities of 1,2,3-Triazole Glycoside Clickamers

et al. 2020

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Bacterial resistance remains a significant threat and a leading cause of death worldwide, despite massive attempts to control infections. In an effort to develop biologically active antibacterial and antifungal agents, six novel aryl-substituted-1,2,3-triazoles linked to carbohydrate units were synthesized through the Cu(I)-catalyzed azide-alkyne cycloaddition CuAAC of substituted-arylazides with a selection of alkyne-functionalized sugars. The chemical structures of the new derivatives were verified using different spectroscopic techniques. The novel clicked 1,2,3-triazoles were evaluated for in vitro antibacterial activity against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, and the obtained results were compared with the activity of the reference antibiotic “Ampicillin”. Likewise, in vitro antifungal activity of the new 1,2,3-triazoles was investigated against Candida albicans and Aspergillus niger using “Nystatin” as a reference drug. The results of the biological evaluation pointed out that Staphylococcus aureus was more susceptible to all of the tested compounds than other examined microbes. In addition, some tested compounds exhibited promising antifungal activity.

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Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Antimicrobial Activities of 1,2,3-Triazole Glycoside Clickamers

et al. 2020

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“…In this case, an average yield of 83% (Compounds C1 to D5, Table 1) was obtained. Our group has previously reported that geranylazide exists in solution as a mixture of inseparable regioisomers [24,25], which after the cycloaddition stage allows to generate the E and Z isomers in a 3:2 ratio [26,27]. Although in some cases it is possible to separate the E and Z triazoles obtained from this azide mixture, in this case, due to the polarity of both diasteroisomers, all attempts to obtain pure isomers by chromatographic separation were unsuccessful.…”

Section: Synthesismentioning

confidence: 99%

Systematic study of 1,2,3-triazolyl sterols for the development of new drugs against parasitic Neglected Tropical Diseases

Porta

Ballari

Carlucci

et al. 2023

European Journal of Medicinal Chemistry

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“…In general, statins compromised the pathogen's ability of immune evasion and survival, associated with a deficit of host-derived MVA pathway intermediates [103][104][105]. Similarly, the MEP-pathway has also been found to be an interesting drug target against Plasmodium falciparum [30,[106][107][108], Toxoplasma gondii [109], Babesia microti [110], or Mycobacterium tuberculosis [111]. Furthermore, fosmidomycin has already been evaluated in several clinical trials as a promising treatment for malaria, albeit with limited success [112].…”

Section: Infectious Diseasesmentioning

confidence: 99%

The Biomedical Importance of the Missing Pathway for Farnesol and Geranylgeraniol Salvage

et al. 2022

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Isoprenoids are the output of the polymerization of five-carbon, branched isoprenic chains derived from isopentenyl pyrophosphate (IPP) and its isomer, dimethylallyl pyrophosphate (DMAPP). Isoprene units are consecutively condensed to form longer structures such as farnesyl and geranylgeranyl pyrophosphate (FPP and GGPP, respectively), necessary for the biosynthesis of several metabolites. Polyprenyl transferases and synthases use polyprenyl pyrophosphates as their natural substrates; however, it is known that free polyprenols, such as farnesol (FOH), and geranylgeraniol (GGOH) can be incorporated into prenylated proteins, ubiquinone, cholesterol, and dolichols. Furthermore, FOH and GGOH have been shown to block the effects of isoprenoid biosynthesis inhibitors such as fosmidomycin, bisphosphonates, or statins in several organisms. This phenomenon is the consequence of a short pathway, which was observed for the first time more than 25 years ago: the polyprenol salvage pathway, which works via the phosphorylation of FOH and GGOH. Biochemical studies in bacteria, animals, and plants suggest that this pathway can be carried out by two enzymes: a polyprenol kinase and a polyprenyl-phosphate kinase. However, to date, only a few genes have been unequivocally identified to encode these enzymes in photosynthetic organisms. Nevertheless, pieces of evidence for the importance of this pathway abound in studies related to infectious diseases, cancer, dyslipidemias, and nutrition, and to the mitigation of the secondary effects of several drugs. Furthermore, nowadays it is known that both FOH and GGOH can be incorporated via dietary sources that produce various biological effects. This review presents, in a simplified but comprehensive manner, the most important data on the FOH and GGOH salvage pathway, stressing its biomedical importance The main objective of this review is to bring to light the need to discover and characterize the kinases associated with the isoprenoid salvage pathway in animals and pathogens.

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Repositioning Salirasib as a new antimalarial agent

Abstract: Repurposing strategies present an enormous advantage for drug discovery, especially in malaria, where resources are scarce.

Cited by 19 publications

References 33 publications

Design, Synthesis, and Antimicrobial Activities of 1,2,3-Triazole Glycoside Clickamers

Design, Synthesis, and Antimicrobial Activities of 1,2,3-Triazole Glycoside Clickamers

Systematic study of 1,2,3-triazolyl sterols for the development of new drugs against parasitic Neglected Tropical Diseases

The Biomedical Importance of the Missing Pathway for Farnesol and Geranylgeraniol Salvage

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