Synthetic chalcones as efficient inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase PtpA

Chiaradia, Louise Domeneghini; Mascarello, Alessandra; Purificação, Marcela; Vernal, Javier; Cordeiro, Mabel Mariela Rodríguez; Zenteno, María Emilia; Villarino, Andréa; Nunes, Ricardo José; Yunes, Rosendo A.; Terenzi, Hernán

doi:10.1016/j.bmcl.2008.09.105

Cited by 101 publications

(79 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Figure 6 shows that PtpB activity is optimum at 37 o C and pH of 6.0. These findings are in agreement to the previous reports (Mascarello et al, 2013;Chiaradia et al, 2008). Thus the recovered PtpB produced by this approach is ready to be utilized in the further study, such as screening of novel inhibitors for PtpB.…”

Section: Determination Of Optimum Ptpb Activitysupporting

confidence: 92%

Expression of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B in Escherichia coli and Its Recovery from Inclusion Body

et al. 2017

View full text Add to dashboard Cite

The present study aims at expressing and partially purifying PtpB in active form. To achieve this, Mtb PtpB gene has been cloned into pET30a vector and overexpressed in Escherichia coli BL 21(DE3) under IPTG induction in the form of an inclusion body. Following resolubilization by urea and dialysis, the resulted PtpB has been shown to be active against para-Nitrophenyl phosphate. It is concluded that the resulted PtpB has had been recovered from inclusion body to give the active form of the enzyme, and thus the success in overexpressing PtpB provides the required material to investigate the biochemical properties of the pathogen virulence factor further.

show abstract

Section: Determination Of Optimum Ptpb Activitysupporting

confidence: 92%

Expression of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B in Escherichia coli and Its Recovery from Inclusion Body

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The 110 assayed synthetic compounds (Table S1, Supplementary information), were prepared as described in our previous reports [19][20][21][22][23][24][25][26][27][28][29] . Reagents were obtained from Sigma-Aldrich Õ (St. Louis, MO) and solvents from Vetec (Duque de Caxias, RJ, Brazil).…”

Section: Synthesis and Purification Of The Compoundsmentioning

confidence: 99%

Synthetic compounds from an in house library as inhibitors of falcipain-2 from Plasmodium falciparum

Bertoldo¹,

Chiaradia-Delatorre²,

Mascarello³

et al. 2014

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Falcipain-2 (FP-2) is a key cysteine protease from the malaria parasite Plasmodium falciparum. Many previous studies have identified FP-2 inhibitors; however, none has yet met the criteria for an antimalarial drug candidate. In this work, we assayed an in-house library of non-peptidic organic compounds, including (E)-chalcones, (E)-N'-benzylidene-benzohydrazides and alkylesters of gallic acid, and assessed the activity toward FP-2 and their mechanisms of inhibition. The (E)-chalcones 48, 54 and 66 showed the lowest IC 50 values (8.5 ± 0.8 mM, 9.5 ± 0.2 mM and 4.9 ± 1.3 mM, respectively). The best inhibitor (compound 66) demonstrated non-competitive inhibition, and using mass spectrometry and fluorescence spectroscopy assays, we suggest a potential allosteric site for the interaction of this compound, located between the catalytic site and the hemoglobin binding arm in FP-2. We combined structural biology tools and mass spectrometry to characterize the inhibition mechanisms of novel compounds targeting FP-2.

show abstract

“…Anticancer potential of A novel quinazolinone-chalcone derivative 2- 4, was determined through MTT assay, colony formation assay, Wound healing assay, Cell cycle and Western Blot Analysis in Mia paca-2 cells treated with 8b.…”

Section: Methodsmentioning

confidence: 99%

“…They are considered to be precursors of flavonoids and isoflavonoids which serve in plant defense mechanisms to counteract reactive oxygen species (free radicals) and prevent molecular damage and damage by microorganisms, insects and animals. Chalcones possess multifarious biological activities like anti-inflammatory [2] , antioxidant [3] , antimicrobial [4] , anti-HIV [5] , anti-malarial [6] , anti-allergic [7] and anticancer [8] .…”

mentioning

confidence: 99%

Anticancer activity of a novel quinazolinone-chalcone derivative through cell cycle arrest in pancreatic cancer cell line

Wani¹,

Pathania²,

Mahajan³

et al. 2015

JST

View full text Add to dashboard Cite

Background: Genotoxic effects of many of clinically useful anticancer drugs are due to their interaction with the amino groups of nucleic acids. Literature reveals that the chalcones however may be devoid of this important side effect. With this view in mind, we synthesized a novel quinazolinone-chalcone derivative and evaluated its anticancer potential. Methods:Anticancer potential of A novel quinazolinone-chalcone derivative 2- 4, was determined through MTT assay, colony formation assay, Wound healing assay, Cell cycle and Western Blot Analysis in Mia paca-2 cells treated with 8b. Results:The cytotoxicity studies showed a concentration dependent decrease in cell viability of HCT-116, HL-60, PC-3, A-549, Mia pacca-2 and MCF-7 cell lines with IC 50 values ranging from 5.5 to 8.5 µM. The motility of Mia paca-2 cells treated with 8b was found inhibited in a dose dependent manner. Cell cycle studies revealed a concentration dependent rise in G2/M phase of cell cycle from 1% to 52%. Decreased expression of cyclins regulating G2/M transition of the cell cycle (cyclin B1 and cdk1) was recorded after treatment of Mia Paca-2 cells with 8b. Mitochondrial membrane potential was also significantly lost in cultures exposed to 8b. However, nuclear morphology of 8b treated Mia paca-2 cells revealed no significant changes. 8b significantly inhibited the growth of Ehrlich ascites carcinoma, Sarcoma-180 (ascites), Ehrlich tumor (solid) and Sarcoma-180 (solid). Conclusion:The findings are indicative of 8b exerting anticancer activity through cell cycle arrest at G2/M phase and not through apoptosis. Reduction in the motility of Mia paca-2 cells indicates anti-metastatic potential of 8b.

show abstract

Synthetic chalcones as efficient inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase PtpA

Cited by 101 publications

References 31 publications

Expression of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B in Escherichia coli and Its Recovery from Inclusion Body

Expression of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B in Escherichia coli and Its Recovery from Inclusion Body

Synthetic compounds from an in house library as inhibitors of falcipain-2 from Plasmodium falciparum

Anticancer activity of a novel quinazolinone-chalcone derivative through cell cycle arrest in pancreatic cancer cell line

Contact Info

Product

Resources

About