Efficient One‐Pot Synthesis of 2‐Amino‐4H pyran‐3‐carbonitriles Using Ionic Liquid: Reactions, Quantum‐Chemical Calculations, and Antiproliferative Activity

Author:

Saleh Mariziq Al‐Sarhani Mjd1,Abdelgayed Ahmed Arafa Wael12ORCID,Atef Ghoneim Amira3,Althobaiti Ibrahim O.4,Farok Hussein Modather15,Kamal Mourad Asmaa2

Affiliation:

1. Department of Chemistry College of Science Jouf University Sakaka 72341, Aljouf Saudi Arabia

2. Chemistry Department Faculty of Science Fayoum University P.O. Box 63514 Fayoum Egypt

3. Chemistry Department Faculty of Science Zagazig University Zagazig Egypt

4. Chemistry Department College of Science and Arts Jouf University Gurayat 77217 Saudi Arabia

5. Chemistry Department Faculty of Science Al-Azhar University Asyut branch Asyut 71524 Egypt

Abstract

AbstractA new highly efficient and eco‐friendly protocol utilizing ultrasonic irradiation was established for the assembly of 2‐amino‐4H‐pyran‐3‐carbonitriles series. Outstanding yields (97–99 %) and better reaction profiles were accessible utilizing the atom‐economical approach. Further, three fused pyrimidines were accessible through cyclization reactions of 2‐amino‐5‐oxo‐4‐(thiophen‐2‐yl)‐5,6,7,8‐tetrahydro‐4H‐chromene‐3‐carbonitrile (8 l) with various reagents under sustainable conditions. Moreover, the anti‐proliferative activity of the assembled imidazopyrimidines was in vitro evaluated against three human cancer cell lines, MCF7 (breast cancer), HepG2 (liver cancer), and A549 (lung cancer), and one normal human cell line, MCF‐10 A (human mammary cell line). In comparison to Doxorubicin, the criterion drug, all of the tested compounds exhibited potent cytotoxic effects. The relationship between activity and structure was also addressed. Noteworthy, the quantum chemical investigations of the assembled molecules using Density Functional Theory (DFT) have been studied and found to agree with the observed anti‐proliferative activities. In addition, the docking studies demonstrated that the studied compounds possess low binding energies towards three selected proteins (6ENV‐MCV‐7, 4b3z‐Lung, and HepG2‐2JW2). Finally, the electron distribution on the surface of the assembled compounds has been evaluated by ESP.

Publisher

Wiley

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