1,3-Oxazole derivatives as potential anticancer agents: Computer modeling and experimental study

Semenyuta, Ivan; Kovalishyn, Vasyl; Tanchuk, Vsevolod Yu.; Pilyo, Stepan; Zyabrev, V. S.; Blagodatnyy, V.N.; Trokhimenko, Olena; Броварец, В. С.; Metelytsia, Larysa

doi:10.1016/j.compbiolchem.2016.09.012

Cited by 33 publications

(17 citation statements)

References 23 publications

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“…To understand the connection between the chemical constitution of the 1,3‐oxazole derivatives and their biological activity, particularly, as potential anticancer agents, the detailed study of the qualitative structure‐activity relationship (QSAR) of the some substituted 2‐phenyl‐1,3‐oxazoles were early performed . It was a modeled formation of complex in the binding site of tubulin, and it showed the effective protein‐ligand interaction.…”

Section: Resultsmentioning

confidence: 99%

“…To understand the connection between the chemical constitution of the 1,3-oxazole derivatives and their biological activity, particularly, as potential anticancer agents, the detailed study of the qualitative structure-activity relationship (QSAR) of the some substituted 2-phenyl-1,3-oxazoles were early performed. [2,35] It was a modeled formation of complex in the binding site of tubulin, and it showed the effective protein-ligand interaction. So, the results of molecular docking have indicated the formation of the π-σ interaction between the conjugated systems of the 1,3-oxazole ligand and peptide fragment (σ is lone electron pair at nitrogen atom), which stabilizes the protein-ligand complex; the predicted binding affinity ≈ −7.7 kcal/mol.…”

Section: Quantum-chemical Modeling Of Donor/acceptor Property Of Sumentioning

confidence: 99%

“…1,3‐Oxazoles play a vital role in the manufacture of various biologically active drugs as brain‐derived neurotrophic factor inducers, analgesic, trypanocidal activity, antimitotic agents with pro‐apoptotic activity, antibacterial and antituberculosis properties, antifungal activity, anti‐inflammatory, antidepressant, antimicrobial, antidiabetic and antiobesity, antiviral, and analgesic effect . Thus, 1,3‐oxazole could be considered as perspective moiety in the design and further synthesis of novel biologically active agents that exert anticancer activity …”

Section: Introductionmentioning

confidence: 99%

“…The heterocyclic compounds with branched conjugated systems including oxazole, thiazole, or pyrazole moieties have shown themselfes as powerful scaffolds in drug design. [1][2][3][4][5][6][7][8][9][10] 1,3-Oxazoles play a vital role in the manufacture of various biologically active drugs as brain-derived neurotrophic factor inducers, [11] analgesic, [12] trypanocidal activity, [13] antimitotic agents with pro-apoptotic activity, [14] antibacterial and antituberculosis properties, [15] antifungal activity, [16] antiinflammatory, [17] antidepressant, [18] antimicrobial, [3] antidiabetic and antiobesity, [19][20][21][22] antiviral, and analgesic effect. [5,6] Thus, 1,3-oxazole could be considered as perspective moiety in the design and further synthesis of novel biologically active agents that exert anticancer activity.…”

Section: Introductionmentioning

confidence: 99%

“…[5,6] Thus, 1,3-oxazole could be considered as perspective moiety in the design and further synthesis of novel biologically active agents that exert anticancer activity. [1][2][3][4][23][24][25][26][27][28][29][30][31][32][33][34] So, the QSAR models were developed for wide site of 1,3-oxazole derivatives showing inhibitory effect on the NCI-60 cancer cell lines, [2,35] and the well correlation was established between many descriptors and biological activity. So, it was investigated the interaction of the azole derivatives with the tubulin inhibitors which significantly improve the clinical effectivity of novel proposed biological active molecules as anticancer agents.…”

Section: Introductionmentioning

confidence: 99%

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Dependence of the anticancer activity of 1,3‐oxazole derivatives on the donor/acceptor nature of his substitues

Kachaeva

Hodyna

Obernikhina

et al. 2019

Journal of Heterocyclic Chem

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A series of new 1,3‐oxazole derivatives, containing in position 5 both donor and acceptor substituents were synthesized. These substances were considered as potentially active anticancer pharmacophores in the human tumor cell line panel derived from nine cancer types, including lung, colon, melanoma, renal, ovarian, brain, leukemia, breast, and prostate. Primary in vitro one‐dose anticancer screening was shown that compounds with acceptor substituents (such as –C(O)OMe, –CN) in the position 5 inhibit the growth of most cell lines, and compounds with donor substituents (such as –NHR, −SR) in the position 5 do not practically inhibit the growth of cancer cell lines. It can be assumed that the pharmacological activity of 1,3‐oxazole derivatives depends on donor/acceptor nature of the substituents in position 5. It was proposed to evaluate the donor/acceptor ability of 1,3‐oxazole derivatives using the special parameter φ0, which takes into account the relative position of the boundary levels (HOMO end LUMO). The quantum‐chemical modeling was performed; the special parameter φ0 for 1,3‐oxazole derivatives correlates with the experimental results. Quantum‐chemical calculations of the special parameter φ0 allow modeling the pharmacological activity of 1,3‐oxazole derivatives by introducing donor or acceptor substituents at position 2 or 5. This work may be useful for chemists to develop a target synthesis of potential biologically active compounds.

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Section: Resultsmentioning

confidence: 99%

Section: Quantum-chemical Modeling Of Donor/acceptor Property Of Sumentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dependence of the anticancer activity of 1,3‐oxazole derivatives on the donor/acceptor nature of his substitues

Kachaeva

Hodyna

Obernikhina

et al. 2019

Journal of Heterocyclic Chem

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Diphenylphosphoryl Azide (DPPA)‐Mediated One‐Pot Synthesis of Oxazolo[4,5‐c][1,8]naphthyridin‐4(5 H)‐ones, Oxazolo[4,5‐c]quinoline‐4(5 H)‐ones, and Tosyloxazol‐5‐yl Pyridines

et al. 2017

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An operationally facile and efficient protocol has been developedf or the construction of various 1,3-oxazolecontaining heterocycles with excellent yields of up to 94 %. This protocol proceeds through ad iphenylphosphoryl azide (DPPA)-mediatedr eactionc ascade on substituted 2-aminonicotinic acids/2-aminoanthranilic acids with ethyl isocyanoacetate/p-toluenesulfonylmethyl isocyanides by forming CÀC, CÀO, andC ÀNb onds in as ingle operation. The synthetic utility of this transformation is also extendedt hrough as caled-up synthesisa nd CÀHa ctivation.T he salient features such as metal-free, mild reaction conditions, higher yields, and clean reactions make the protocol auseful contribution to the synthesis of medicinally useful heterocycles.

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Synthesis, characterization of novel N‐(4‐cyano‐1,3‐oxazol‐5‐yl)sulfonamide derivatives and in vitro screening their activity against NCI‐60 cancer cell lines

Severin,

Pilyo,

Kachaeva

et al. 2024

ChemMedChem

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A novel series of N‐(4‐cyano‐1,3‐oxazol‐5‐yl)sulfonamides have been synthesized and characterized by IR, 1H NMR, 13C NMR spectroscopy, elemental analysis and chromato‐mass‐spectrometry. The anticancer activities of all newly synthesized compounds were еvaluated via a single high‐dose assay (10 µM) against 60 cancer cell lines by the National Cancer Institute (USA) according to its screening protocol. Among them, compounds 2 and 10 exhibited the highest activity against the 60 cancer cell lines panel in the one‐dose assay. Compounds 2 and 10 showed inhibitory activity within the GI50 parameter and in five dose analyses. However, their cytostatic activity was only observed against some cancer cell lines, and cytotoxic concentration was outside the maximum used, i.e., > 100 µM. The COMPARE analysis showed that the average graphs of the tested compounds have a moderate positive correlation with compounds with the L‐cysteine analog and vinblastine (GI50) as well as paclitaxel (TGI), which target microtubules. Therefore, disruption of microtubule formation may be one of the mechanisms of the anticancer activity of the tested compounds, especially since among tubulin inhibitors with antitumor activity, compounds with an oxazole motif are widely represented. Therefore, N‐(4‐cyano‐1,3‐oxazol‐5‐yl)sulfonamides may be promising for further functionalization to obtain more active compounds.

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1,3-Oxazole derivatives as potential anticancer agents: Computer modeling and experimental study

Cited by 33 publications

References 23 publications

Dependence of the anticancer activity of 1,3‐oxazole derivatives on the donor/acceptor nature of his substitues

Dependence of the anticancer activity of 1,3‐oxazole derivatives on the donor/acceptor nature of his substitues

Diphenylphosphoryl Azide (DPPA)‐Mediated One‐Pot Synthesis of Oxazolo[4,5‐c][1,8]naphthyridin‐4(5 H)‐ones, Oxazolo[4,5‐c]quinoline‐4(5 H)‐ones, and Tosyloxazol‐5‐yl Pyridines

Synthesis, characterization of novel N‐(4‐cyano‐1,3‐oxazol‐5‐yl)sulfonamide derivatives and in vitro screening their activity against NCI‐60 cancer cell lines

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