Efficient synthesis and molecular docking studies of new pyrimidine-chromeno hybrid derivatives as potential antiproliferative agents
Date
26 May 202Metadata
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aDepartment of Chemistry, Faculty of Science, Erciyes University, Kayseri, Turkey; bDepartment of Veterinary Science, S¸efaatli Vocational School, Yozgat Bozok University, Yozgat, Turkey; cDepartment of Basic Pharmaceutical Sciences, Faculty of Pharmacy, S€uleyman Demirel University, Isparta, Turkey; dDepartment of Chemistry, Faculty of Science, Sivas Cumhuriyet University, Sivas, Turkey; eScientific and Technological Research Application and Research Center, Sinop University, Sinop, TurkeyAbstract
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.