Design, synthesis, molecular docking and in silico ADMET profile of pyrano[2,3-d]pyrimidine derivatives as antimicrobial and anticancer agents

Bioorg Chem. 2021 Jul 22;115:105186. doi: 10.1016/j.bioorg.2021.105186. Online ahead of print.ABSTRACTPyrano[2,3-d]pyrimidine derivatives were synthesized by treating cyclic compounds containing active methylene group with aldehyde and malononitrile in butanol. The behavior of pyrano[2,3-d]pyrimidine towards some electrophlies namely triethylorthoformate followed by nitrogen nucleophiles as isobutylamine, urea, phenylthiourea, p-toluidine, o-phenylenediamine, o-aminophenol, 2-amino-4-methyl-pyridine and acetic acid with the aim of obtaining some interesting non-mixed heterocyclic compounds. All synthesized compounds to some extent have shown good antimicrobial activity against different microbial strains that had been extracted by inhibiting cell wall synthesis. Compound 5b showed the highest antibacterial activities against B. subtilis, S. aureus and E. coli. On the other hand compound 5 g exhibited the highest antibacterial and antifungal activities against P. aeruginosa and A. niger respectively. In addition, they explore cytotoxic potentialities against different cell lines via DNA intercalation and Top-II inhibition. The cytotoxic activities clarify the strong inhibitory activity of derivative 5a against HepG2 cells with IC50 = 2.09 μM, while HCT-116 cells were highly susceptible to derivative 5c with IC50 = 2.61 μM, in the meantime, derivative 5f showed pronounced negative impact against MCF-7 (IC50 = 2.43 μM) when compared with other prepared compounds. All derivati...
Source: Bioorganic Chemistry - Category: Chemistry Authors: Source Type: research