Synthesis and Antiproliferative Activity of a New Series of Mono- and Bis(dimethylpyrazolyl)-s-triazine Derivatives Targeting EGFR/PI3K/AKT/mTOR Signaling Cascades was written by Shawish, Ihab;Barakat, Assem;Aldalbahi, Ali;Malebari, Azizah M.;Nafie, Mohamed S.;Bekhit, Adnan A.;Albohy, Amgad;Khan, Alamgir;Ul-Haq, Zaheer;Haukka, Matti;de la Torre, Beatriz G.;Albericio, Fernando;El-Faham, Ayman. And the article was included in ACS Omega in 2022.Computed Properties of C9H6Cl2N4 The following contents are mentioned in the article:
Here, we synthesized a newseries of mono- and bis(dimethylpyrazolyl)-s-triazine derivatives The synthetic methodol. 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 ± 0.30μM (MCF-7); 0.50 ± 0.080μM (HCT-116); and 3.01 ± 0.49μM (HepG2)]; 5d [(IC50 = 3.66 ± 0.96μM (HCT-116); and 5.42 ± 0.82μM (HepG2)]; and 5c [(IC50 = 2.29 ± 0.92μM (MCF-7)]. Mol. 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%, resp., at a concentration of 10μM. 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, resp.). 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. This study involved multiple reactions and reactants, such as 4,6-Dichloro-N-phenyl-1,3,5-triazin-2-amine (cas: 2272-40-4Computed Properties of C9H6Cl2N4).
4,6-Dichloro-N-phenyl-1,3,5-triazin-2-amine (cas: 2272-40-4) belongs to organic chlorides. Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids. Organochlorine compounds are lipophylic, meaning they are more soluble in fat than in water. This gives them a high tenancy to accumulate in the food chain (biomagnification).Computed Properties of C9H6Cl2N4
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics