The anti-cancer potential of 2,4,6 tris-methyphenylamino1,3,5-triazine compound against mammary glands cancer: Via down-regulating the hormonal, inflammatory mediators, and oxidative stress

Mehmood, Yumna; Anwar, Fareeha; Saleem, Uzma; Hira, Sundas; Ahmad, Bashir; Bashir, Manal; Imtiaz, Muhammad Tayyab; Najm, Saima; Ismail, Tariq

doi:10.1016/j.lfs.2021.119994

Cited by 5 publications

(1 citation statement)

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“…The widespread importance of the synthesis and modification of anticancer agents has given rise to many numbers of medicinal chemistry programs. In this regard, s -triazine derivatives have attracted attention due to their remarkable activity against a wide range of cancer cells. − Hexalen, also known as Altretamine (Figure , compound I ), which was first approved by the U.S. Food and Drug Administration (U.S. FDA) in 1990, is an example of an antineoplastic drug based on an s -triazine privileged structure, and it is used for the treatment of refractory ovarian cancer . Other examples of commercial drugs based on the s -triazine moiety include Enasidenib (Idhifa) (Figure , compound II ), which is used to treat IDH2-positive acute leukemia and was first approved by the U.S. FDA in 2017, and Gedatolisib (Figure , compound III ), a first-in-class PI3K/mTOR inhibitor used to treat breast cancer .…”

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confidence: 99%

Synthesis and Antiproliferative Activity of a New Series of Mono- and Bis(dimethylpyrazolyl)-s-triazine Derivatives Targeting EGFR/PI3K/AKT/mTOR Signaling Cascades

et al. 2022

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Here, 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-1 H -pyrazol-1-yl)-6-morpholino-1,3,5-triazin-2-amine 4f , N -(4-chlorophenyl)-4,6-bis(3,5-dimethyl-1 H -pyrazol-1-yl)-1,3,5-triazin-2-amine 5c , and 4,6- bis (3,5-dimethyl-1 H -pyrazol-1-yl)- N -(4-methoxyphenyl)-1,3,5-triazin-2-amine 5d showed promising activity against these cancer cells: 4f [(IC 50 = 4.53 ± 0.30 μM (MCF-7); 0.50 ± 0.080 μM (HCT-116); and 3.01 ± 0.49 μM (HepG2)]; 5d [(IC 50 = 3.66 ± 0.96 μM (HCT-116); and 5.42 ± 0.82 μM (HepG2)]; and 5c [(IC 50 = 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 IC 50 value of 61 nM compared to that of Tamoxifen (IC 50 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.

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