Design and synthesis of pyrimidinyl acyl thioureas as novel Hsp90 inhibitors in invasive ductal breast cancer and its bone metastasis

Koca, İrfan; Özgür, Aykut; Er, Muhammet; Gümüş, Mehmet; Coşkun, Kübra Açıkalın; Tutar, Yusuf

doi:10.1016/j.ejmech.2016.06.032

Cited by 40 publications

(26 citation statements)

References 37 publications

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“…The IR spectra of compounds 1 and 2 have C=O, C=S and N-H stretching bands of acylthiourea group at 1674-1675 cm , and 3256-3274 cm -1 , respectively (7,43). In the 1 H-NMR spectra of compound 2, resonances assigned to the N 1 -H and N 2 -H protons of thiourea were detected between 8.83-13.28 ppm as three broad singlets, which are supported by the literature (7,44,45).…”

Section: Whensupporting

confidence: 65%

Tiyoüreler, açiltiyoüreler ve 4-tiyazolidinonların sentezi, karakterizasyonu ve antikanser ve antiviral etkilerinin değerlendirilmesi

Kulabaş¹,

Özakpınar²,

Özsavcı³

et al. 2017

Marmara Pharmaceutical Journal

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In this study, thiourea derivatives [1][2][3][4] were synthesized by using 2-amino-4-substituted pyridine compounds and these compounds have been used as the starting materials for synthesis of 2-imino-1,3-thiazolidin-4-one ring [5,6]. Two different procedures for 4-thiazolidinone ring closure and synthesis method were optimized. The synthesized compounds were identified by the help of elemental analysis, IR, 1 H-NMR, 13 C-NMR and mass spectral data while the purities of them were proved with TLC. Synthesized compounds were evaluated for their antiviral and anticancer activity. Antiviral activity against Murine norovirus, Yellow fever, Enterovirus and Chikungunya strains of the test compounds were investigated and EC 50 values of these compounds were determined higher than 0,3 µM. Cytotoxicity of test compounds was examined on NIH3T3 cell line. When the anticancer activity of test compounds was examined against PC-3, A549, HeLa, HT-29, MCF-7, SJSA1 and K562 cell lines, the percent proliferation values of these compounds were observed over 61% for all cell lines.

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Section: Whensupporting

confidence: 65%

Tiyoüreler, açiltiyoüreler ve 4-tiyazolidinonların sentezi, karakterizasyonu ve antikanser ve antiviral etkilerinin değerlendirilmesi

Kulabaş¹,

Özakpınar²,

Özsavcı³

et al. 2017

Marmara Pharmaceutical Journal

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“…We began our investigation with the reaction of ethyl benzoyl acetate and oxalyl chloride. The synthesis reactions in the first four steps had been indicated in our previous study . In the last step, treatment of pyrimidinyl carbonyl chloride ( 4 ) with aromatic amines in xylene in the presence of pyridine resulted in the synthesis of target compounds.…”

Section: Resultsmentioning

confidence: 99%

“…Pyrimidine compounds are found in a variety of naturally occurring compounds and biologically active molecules . They have been reported to have various biological activities acting as antitumor, antiviral, anti‐inflammatory, anti‐anxiety or antimicrobial agents. Among the pyrimidine derivatives, pyrimidine carboxamides represent a promising class of bioactive substances and are of particular interest in the medical fields.…”

Section: Introductionmentioning

confidence: 99%

“…In our previous work, we evaluated anticancer properties of pyrimidinyl acylthiourea compounds on human invasive ductal breast (MCF‐7) and human bone osteosarcoma (Saos‐2) cell lines . Considering the potential biological activity of pyrimidine carboxamides and our earlier work we decided to prepare novel pyrimidine‐5‐carboxamide derivatives.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Experimental and Theoretical Characterization of Novel Pyrimidine‐5‐Carboxamides

Gümüş

Sert

Yalkın³

et al. 2019

ChemistrySelect

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Eight series of pyrimidine‐5‐carboxamides were synthesized and characterized by FT‐IR, 1H NMR, 13C NMR spectroscopies, HR‐MS and elemental analysis. To encourage experimental confirmations, molecular electronic structure calculations and harmonic vibrational frequencies of compounds (theoretical computations) were carried out with the DFT/B3LYP method at the 6–311G++(d,p) basis set. The selected important assignments‐computed harmonic vibrational wavenumbers of compounds were defined by using potential energy distribution (PED) analysis. The molecular electrostatic potential (MEP) surface analysis was examined to bring into the open nucleophilic and electrophilic reactive areas of the compounds. The highest occupied molecular orbitals and lowest unoccupied molecular orbitals (HOMOs and LUMOs) analyses were theoretically used for definition of electronic transitions corresponding to UV‐Vis. electronic absorption wavelengths. Additionally, for these series non‐linear optical properties (NLO) were investigated based on urea. Finally, in this manuscript molecular docking studies between macromolecule (receptor) and ligand interactions were carried out by using AutoDock Vina program. Obtained all outputs of new compounds were explained in different sections in‐depth.

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“…The activity of Hsp90 is regulated by the binding and hydrolysis of ATP to ADP (adenosine diphosphate) at the Nterminal domain. Thus, tremendous efforts have recently been performed to find inhibitors capable of binding to the ATP-binding cavity to arrest the function of Hsp90 [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Insight into the Interaction of Cationic Porphyrin-Anthraquinone Hybrids with Hsp90: In Silico Analysis

et al. 2018

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Heat shock protein 90 (Hsp90) is responsible for the correct folding of many cellular proteins. Several Hsp90 inhibitors have been developed for cancer treatment. The present in silico study aimed to evaluate the potential of several porphyrin derivatives conjugated with anthraquinone groups as Hsp90 inhibitors by using simulation of molecular docking and molecular dynamics. The binding mode of porphyrin hybrids to Hsp90, which was examined by using AutoDock 4.2, showed that all six porphyrin compounds fit well in the binding pocket of Hsp90. The pi-cationic interactions with Lys58 were exclusively observed in the interaction of each porphyrin hybrid. Stabilities of porphyrin-Hsp90 complexes were confirmed by 40-ns MD simulation, which was carried out with the help of AMBER16. Prediction of ligand affinity by using the MM-PBSA method showed that all complexes were energetically favorable as indicated by a negative binding free energy. The predicted affinities of tris−H 2 PyP−AQ, tris−H 2 PzP−AQ, bis−H 2 PzP−AQ, and mono−H 2 PzP−AQ are better than those of geldanamycin, a known inhibitor of Hsp90, which shows the importance of the electrostatic and van der Waals energies for ligand binding.

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Design and synthesis of pyrimidinyl acyl thioureas as novel Hsp90 inhibitors in invasive ductal breast cancer and its bone metastasis

Cited by 40 publications

References 37 publications

Tiyoüreler, açiltiyoüreler ve 4-tiyazolidinonların sentezi, karakterizasyonu ve antikanser ve antiviral etkilerinin değerlendirilmesi

Tiyoüreler, açiltiyoüreler ve 4-tiyazolidinonların sentezi, karakterizasyonu ve antikanser ve antiviral etkilerinin değerlendirilmesi

Synthesis, Experimental and Theoretical Characterization of Novel Pyrimidine‐5‐Carboxamides

Insight into the Interaction of Cationic Porphyrin-Anthraquinone Hybrids with Hsp90: In Silico Analysis

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