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dc.contributor.authorShawish, Ihab
dc.contributor.authorBarakat, Assem
dc.contributor.authorAldalbahi, Ali
dc.contributor.authorMalebari, Azizah M.
dc.contributor.authorNafie, Mohamed S.
dc.contributor.authorBekhit, Adnan A.
dc.contributor.authorAlbohy, Amgad
dc.contributor.authorKhan, Alamgir
dc.contributor.authorUl-Haq, Zaheer
dc.contributor.authorHaukka, Matti
dc.contributor.authorde la Torre, Beatriz G.
dc.contributor.authorAlbericio, Fernando
dc.contributor.authorEl-Faham, Ayman
dc.date.accessioned2022-08-23T05:57:24Z
dc.date.available2022-08-23T05:57:24Z
dc.date.issued2022
dc.identifier.citationShawish, I., Barakat, A., Aldalbahi, A., Malebari, A. M., Nafie, M. S., Bekhit, A. A., Albohy, A., Khan, A., Ul-Haq, Z., Haukka, M., de la Torre, B. G., Albericio, F., & El-Faham, A. (2022). Synthesis and Antiproliferative Activity of a New Series of Mono- and Bis(dimethylpyrazolyl)-<i>s</i>-triazine Derivatives Targeting EGFR/PI3K/AKT/mTOR Signaling Cascades. <i>ACS Omega</i>, <i>7</i>(28), 24858-24870. <a href="https://doi.org/10.1021/acsomega.2c03079" target="_blank">https://doi.org/10.1021/acsomega.2c03079</a>
dc.identifier.otherCONVID_148907875
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/82760
dc.description.abstractHere, we synthesized a newseries of mono- and bis(dimethylpyrazolyl)-s-triazine derivatives. The synthetic methodology involved the reaction of different mono- and dihydrazinyl-s-triazine derivatives with acetylacetone in the presence of triethylamine to produce the corresponding target products in high yield and purity. The antiproliferative activity of the novel mono- and bis(dimethylpyrazolyl)-s-triazine derivatives was studied against three cancer cell lines, namely, MCF-7, HCT-116, and HepG2. N-(4-Bromophenyl)-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-morpholino-1,3,5-triazin-2-amine 4f, N-(4-chlorophenyl)-4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-amine 5c, and 4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-(4-methoxyphenyl)-1,3,5-triazin-2-amine 5d showed promising activity against these cancer cells: 4f [(IC50 = 4.53 ± 0.30 μM (MCF-7); 0.50 ± 0.080 μM (HCT-116); and 3.01 ± 0.49 μM (HepG2)]; 5d [(IC50 = 3.66 ± 0.96 μM (HCT-116); and 5.42 ± 0.82 μM (HepG2)]; and 5c [(IC50 = 2.29 ± 0.92 μM (MCF-7)]. Molecular docking studies revealed good binding affinity with the receptor targeting EGFR/PI3K/AKT/mTOR signaling cascades. Compound 4f exhibited potent EGFR inhibitory activity with an IC50 value of 61 nM compared to that of Tamoxifen (IC50 value of 69 nM), with EGFR inhibition of 83 and 84%, respectively, at a concentration of 10 μM. Interestingly, 4f showed remarkable PI3K/AKT/mTOR inhibitory activity with 0.18-, 0.27-, and 0.39-fold decrease in their concentration (reduction in controls from 6.64, 45.39, and 86.39 ng/mL to 1.24, 12.35, and 34.36 ng/mL, respectively). Hence, the synthetic 1,3,5-triazine derivative 4f exhibited promising antiproliferative activity in HCT-116 cells through apoptosis induction by targeting the EGFR and its downstream pathway.en
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherAmerican Chemical Society (ACS)
dc.relation.ispartofseriesACS Omega
dc.rightsCC BY-NC-ND 4.0
dc.titleSynthesis and Antiproliferative Activity of a New Series of Mono- and Bis(dimethylpyrazolyl)-<i>s</i>-triazine Derivatives Targeting EGFR/PI3K/AKT/mTOR Signaling Cascades
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-202208234298
dc.contributor.laitosKemian laitosfi
dc.contributor.laitosDepartment of Chemistryen
dc.contributor.oppiaineEpäorgaaninen ja analyyttinen kemiafi
dc.contributor.oppiaineEpäorgaaninen kemiafi
dc.contributor.oppiaineInorganic and Analytical Chemistryen
dc.contributor.oppiaineInorganic Chemistryen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.type.coarhttp://purl.org/coar/resource_type/c_2df8fbb1
dc.description.reviewstatuspeerReviewed
dc.format.pagerange24858-24870
dc.relation.issn2470-1343
dc.relation.numberinseries28
dc.relation.volume7
dc.type.versionpublishedVersion
dc.rights.copyright© 2022 The Authors. Published by American Chemical Society
dc.rights.accesslevelopenAccessfi
dc.format.contentfulltext
dc.rights.urlhttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.relation.doi10.1021/acsomega.2c03079
jyx.fundinginformationThe authors would like to extend their sincere appreciation to the Researchers Supporting Project (RSP-2021/64), King Saud University, Riyadh, Saudi Arabia. This work was partially funded by National Research Foundation (NRF) (Blue Sky’s Research Programme No. 120386).
dc.type.okmA1


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