Efficient synthesis and molecular docking studies of new pyrimidine-chromeno hybrid derivatives as potential antiproliferative agents

Abstract

Various novel heterocyclic compounds containing pyrimidine nuclei 5H-chromeno[4,3-d]pyrimidine (4a–c, e–h, l–r, t) and pyrimidine-5-yl-(2-hydroxyphenyl)methanone (5a, c, d, f–k, m–o, r, s, u) were synthesized from the reaction of guanylhydrazones (2a–u) and 3-formylchromone (3). These compounds were tested against human liver hepatocellular carcinoma cell line (HepG2) and human breast adenocarcinoma cell line (MDA-MB-231) using the MTT assay method. Furthermore, molecular docking calculations were performed to compare the biological activities of various novel heterocyclic compounds against cancer proteins. In these calculations, the protein used are crystal structure of the BRCT repeat region from the breast cancer associated protein, 1JNX, crystal structure of VEGFR kinase (liver cancer) protein, 3WZE, and crystal structure of an allosteric Eya2 phosphates inhibitor (lung cancer) protein, 5ZMA, respectively. After molecular docking calculations, absorption, distribution, metabolism, and excretion/toxicity analysis was performed to examine the properties of various novel heterocyclic compounds for their future use as drugs.

Graphical Abstract

Keywords:

• Antiproliferative activity
• HepG2
• MDA-MB-231
• pyrimidine
• molecular docking

Acknowledgments

This work was financially supported by the Research Fund of Erciyes Üniversitesi [FDK-2016-6664]. The authors acknowledge the Scientific and Technological Research Application and Research Center, Sinop University, Turkey, for the use of the Bruker D8 QUEST diffractometer. This research was made possible by TUBITAK ULAKBIM, High Performance and Grid Computing Center (TR-Grid e-Infrastructure).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was financially supported by Erciyes University Research Fund [FDK-2016-6664].