Design, synthesis, in silico molecular docking, and ADMET studies of quinoxaline-isoxazole-piperazine conjugates as EGFR-targeting agents.

In this paper, we report the synthesis of quinoxaline-isoxazole-piperazine conjugates. The anticancer activity was evaluated against three human cancer cell lines, including MCF-7 (breast), HepG-2 (liver), and HCT-116 (colorectal). The outcomes of the tested compounds 5d, 5e, and 5f have shown more potent activity when compared to the standard drug erlotinib. In a cell survivability test (MCF-10A), three potent compounds (5d, 5e, and 5f) were evaluated against the normal breast cell line, although neither of them displayed any significant cytotoxicity with IC50 values greater than 84 µM. Furthermore, the compounds 5d, 5e, and 5f were tested for tyrosine kinase EGFR inhibitory action using erlotinib as the reference drug and compound 5e was shown to be more potent in inhibiting the tyrosine kinase EGFR than sorafenib. In addition to this, molecular docking studies of compounds 5d, 5e, and 5f demonstrated that these compounds had more EGFR-binding interactions. The potent compounds 5d, 5e, and 5f were subjected to in silico pharmacokinetic assessment by SWISS, ADME, and pkCSM. While the compounds 5d, 5e, and 5f followed Lipinski, Veber, Egan, and Muegge rules without any deviation.

Design, Synthesis, and Molecular Docking Studies of Some New Quinoxaline Derivatives as EGFR Targeting Agents.

The synthesis of some new quinoxaline derivatives (IVa-n) and their structure determination using 1H NMR, 13C NMR and mass spectral analysis was described herein. The in vitro anti-cancer activity of the these compounds (IVa-n) revealed that the compound1-((1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(tetrazolo[1,5-a]quinoxalin-4-yl)pyrazolidine-3,5-dione (IVd) has shown promising activity, whereas, compounds 1-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-2-(tetrazolo[1,5-a]quinoxalin-4-yl)pyrazolidine-3,5-dione (IVa), 1-(tetrazolo[1,5-a]quinoxalin-4-yl)-2-((1-(m-tolyl)-1H-1,2,3-triazol-4-yl)methyl)pyrazolidine-3,5-dione (IVb), 1-((1-(3,5-dimethoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(tetrazolo[1,5-a]quinoxalin-4-yl)pyrazolidine-3,5-dione (IVh) and 1-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(tetrazolo[1,5-a]quinoxalin-4-yl)pyrazolidine-3,5-dione (IVi) exhibited good to moderate activity against four human cancer cell lines such as HeLa, MCF-7, HEK 293T, and A549 as compared to the doxorubicin. Predominantly, the compound displayed excellent activity over HeLa, MCF-7, HEK 293T, and A549 with IC50 values of 3.20 ± 1.32, 4.19 ± 1.87, 3.59 ± 1.34, and 5.29 ± 1.34 µM, respectively. Moreover, molecular docking studies of derivatives (IVa-n) on EGFR receptor suggested that the most potent compound strongly binds to protein EGFR (pdbid:4HJO) and the energy calculations of in silico studies were also in good agreement with the obtained IC50 values. Supplementary Information: The online version contains supplementary material available at 10.1134/S1068162022030220.

One-pot synthesis of 3-aminofurans using a simple and efficient recyclable CuI/[bmim]PF6 system.

A one-pot three-component reaction of several 2-ketoaldehydes, secondary amines and terminal alkynes to access 3-aminofurans proceeded well in [bmim][PF6] using a simple and cheap CuI catalyst. The resultant 3-aminofuran products were easily isolated using diethyl ether and the CuI/[bmim][PF6] system was reused six times with a slight decrease in the activity.

Pd-N-heterocyclic carbene catalyzed synthesis of piperidine alkene-alkaloids and their anti-cancer evaluation.

A facile synthesis of piperidine alkene-alkaloids including natural (+)-Caulophyllumine B in high yields has been developed by Heck cross-coupling reaction catalyzed by simple in situ formed palladium-N-heterocyclic carbenes (Pd-NHCs). Formation of Pd(0) nanoparticles has been noticed during the reaction course. The synthesized piperidine alkene-alkaloids were evaluated for in vitro anti-cancer activity against a panel of human tumor cell lines of lung, breast and ovarian. Several of these piperidine alkene-alkaloids were found to possess highest growth inhibition activity than the standard drug cisplatin and support the concept to modulate drug receptor interaction.