Synthetic Approaches for Sulfur Derivatives Containing 1,2,4-Triazine Moiety: Their Activity for &lt;i&gt;in Vitro&lt;/i&gt; Screening towards Two Human Cancer Cell Lines

Karczmarzyk, Zbigniew; Wysocki, Waldemar; Urbańczyk‐Lipkowska, Zofia; Kalicki, Przemysław; Bielawska, Anna; Bielawski, Krzysztof; Ławecka, Justyna

doi:10.1248/cpb.c15-00153

Cited by 17 publications

(8 citation statements)

References 19 publications

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“…Therefore, the secondary amine group in 3a was alkylated to The most commonly used method to synthesize sulfonamide involves the reaction of sulfonyl chlorides with ammonia and amines in an alkaline environment [16,17]. This kind of synthesis has also been studied scientifically by our group, but the low yields prompted us to use the sulfenamide derivatives that are widely known for their medical applications [18][19][20].…”

Section: Synthesismentioning

confidence: 99%

1,2,4-Triazine Sulfonamides: Synthesis by Sulfenamide Intermediates, In Vitro Anticancer Screening, Structural Characterization, and Molecular Docking Study

et al. 2020

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In this study, we synthesized novel sulfonamides with a 1,2,4-triazine moiety according to pharmacophore requirements for biological activity. All the synthesized compounds were tested in vitro to verify whether they exhibited anticancer activity against the human breast cancer cell lines MCF-7 and MDA-MB-231. Among them, two most active ones, having IC50 values of 50 and 42 µM, respectively, were found to show higher anticancer activity than chlorambucil used as the reference in the in vitro tests. In addition, two other compounds, which had IC50 values of 78 and 91 µM, respectively, exhibited a similar level of activity as chlorambucil. X-ray analysis carried out for two of the compounds confirmed their synthesis pathway as well as their assumed molecular structures. Furthermore, a conformational analysis was performed, and electronic parameters of molecules were characterized using theoretical calculations at AM1 and DFT level. Moreover, molecular docking revealed the mode of binding of the investigated 1,2,4-triazine sulfonamides with the human estrogen receptor alpha (ERα).

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Section: Synthesismentioning

confidence: 99%

1,2,4-Triazine Sulfonamides: Synthesis by Sulfenamide Intermediates, In Vitro Anticancer Screening, Structural Characterization, and Molecular Docking Study

et al. 2020

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“…Recently, we have reported a series of sulfur 1,2,4-triazine derivatives and evaluated their as anticancer activity compounds against two human breast cancer cell line (MCF-7 and MDA-MB-231) [ 27 ]. The most effective compound was 5,5′,6,6′-tetraphenylbis(1,2,4-triazin-3-yl)disulfane acting as low micromolar inhibitors with IC 50 = 25 µM.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of unsymmetrical disulfanes bearing 1,2,4-triazine scaffold and their in vitro screening towards anti-breast cancer activity

et al. 2018

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A new series of 1,2,4-triazine unsymmetrical disulfanes were prepared and evaluated as anticancer activity compounds against MCF-7 human breast cancer cells with some of them acting as low micromolar inhibitors. Evaluation of the cytotoxicity using an MTT assay, the inhibition of [3H]-thymidine incorporation into DNA demonstrated that these products exhibit cytotoxic effects on breast cancer cells in vitro. The most effective compounds with 59 and 60 µM compared to chlorambucil with 47 µM were disulfanes bearing methyl and methoxy substituent in an aromatic ring. Furthermore, all new 14 compounds were obtained with 22–74% yield via mild and efficient synthesis of the sulfur–sulfur bond formation from thiols and symmetrical disulfanes using 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ). The molecular structure of the newly obtained compounds was confirmed by X-ray analysis. The conformational preferences of disulfide system were characterized using theoretical calculations at DFT level and statistical distributions of C–S–S–C torsion angle values based on the Cambridge Structural Database (CSD). The DFT calculations and CSD searching show two preferential conformations for C–S–S–C torsion angle close to ± 90° and relatively large freedom of rotation on S–S bond in physiological conditions. The molecular docking studies were performed using the human estrogen receptor alpha (ERα) as molecular target to find possible binding orientation and intermolecular interactions of investigated disulfanes within the active site of ERα. The S…H–S and S…H–C hydrogen bonds between sulfur atoms of bisulfide bridge and S–H and C–H groups of Cys530 and Ala350 as protein residues play crucial role in interaction with estrogen receptor for the most anticancer active disulfane.Graphical abstract Electronic supplementary materialThe online version of this article (10.1007/s00706-018-2206-y) contains supplementary material, which is available to authorized users.

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“…1 ), showed potential antitumor activity against breast cancer cells ( 19 ). Karczmarzyk, et al reported the synthesis and anticancer activity evaluation of a series of sulfur 1,2,4-triazine analogs and introduced 5,5′,6,6′-tetraphenyl-bis-(1,2,4-triazine)-3,3′-disulfide (2) as the most cytotoxic derivative ( 20 )…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, cytotoxicity evaluation and docking studies of 1,2,4-triazine derivatives bearing different arylidene-hydrazinyl moieties as potential mTOR inhibitors

et al. 2018

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Mammalian target of rapamycin (mTOR) is a phosphoinositide 3-kinase-related protein kinase which controls cell growth and is frequently deregulated in many cancers. Therefore, mTOR inhibitors are used as antineoplastic agents for cancer treatment. In this study, 1,2,4-triazine derivatives containing different arylidene-hydrazinyl moieties were designed and synthesized. Cytotoxicity of the compounds was evaluated on HL-60 and MCF-7 cell lines by MTT assay. S1, S2 and S3 exhibited good cytotoxic activity on both cell lines with an IC50 range of 6.42 - 20.20 μM. In general, substitution of a five-membered heterocyclic ring containing NO2, such as 5-nitrofuran-2-yl, resulted in the best potency. Molecular docking analysis was performed to study the possible interactions and binding modes of all the triazine derivatives with mTOR receptor. The most promising compound, S1, was well accommodated within the active site and had the least estimated free energy of binding (even less than the inherent ligand of the protein, PDB ID: 4JT6). It is concluded from both MTT assay and docking studies that the arylidene moiety linked to the hydrazinyl part of the structure had a prominent role in cytotoxicity and mTOR inhibitory activity.

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Synthetic Approaches for Sulfur Derivatives Containing 1,2,4-Triazine Moiety: Their Activity for <i>in Vitro</i> Screening towards Two Human Cancer Cell Lines

Cited by 17 publications

References 19 publications

1,2,4-Triazine Sulfonamides: Synthesis by Sulfenamide Intermediates, In Vitro Anticancer Screening, Structural Characterization, and Molecular Docking Study

1,2,4-Triazine Sulfonamides: Synthesis by Sulfenamide Intermediates, In Vitro Anticancer Screening, Structural Characterization, and Molecular Docking Study

Synthesis of unsymmetrical disulfanes bearing 1,2,4-triazine scaffold and their in vitro screening towards anti-breast cancer activity

Design, synthesis, cytotoxicity evaluation and docking studies of 1,2,4-triazine derivatives bearing different arylidene-hydrazinyl moieties as potential mTOR inhibitors

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