Great attention has been paid to cyclopropenones as they are present in many natural sources.

Spiro-heterocycles have received special attention in medicinal chemistry because of their promising biological activity.

In an attempt to develop effective and safe antibacterial agents, we synthesized novel thiazinanones by combining the quinolone scaffold and the 1,3-thiazinan-4-one group by reaction between ((4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)methylene)hydrazinecarbothioamides and 2,3-diphenylcycloprop-2-enone in refluxing ethanol in the presence of triethyl amine as a catalyst. The structure of the synthesized compounds was characterized by spectral data and elemental analysis, IR, MS, ¹H and ¹³C NMR spectroscopy which showed two doublet signals for CH-5 and CH-6 and four sharp singlets for the protons of thiazinane NH, CHN, quinolone NH and OH, respectively. Also, the ¹³C NMR spectrum clearly showed the presence of two quaternary carbon atoms which were assigned to thiazinanone-C-5 and C-6. All the 1,3-thiazinan-4-one/quinolone hybrids were screened for antibacterial activity. Compounds 7a, 7e and 7g showed broad spectrum antibacterial activity against most of the tested strains either G +ve or G −ve. Compound 7e is the most potent antibacterial agent against MRSA with the minimum inhibitory concentration against MRSA found to be 48 μg mL⁻¹ compared to the drug ciprofloxacin (96 μg mL⁻¹). Additionally, a molecular docking study was performed to understand the molecular interaction and binding mode of the compounds on the active site of S. aureus Murb protein. In silico docking assisted data strongly correlated with the experimental approach of antibacterial activity against MRSA.

Our investigation includes the synthesis of new naphthalene-bis-triazole-bis-quinolin-2(1H)-ones 4a–e and 7a–e via Cu-catalyzed [3 + 2] cycloadditions of 4-azidoquinolin-2(1H)-ones 3a–e with 1,5-/or 1,8-bis(prop-2-yn-1-yloxy)naphthalene (2) or (6). All structures of the obtained products have been confirmed with different spectroscopic analyses. Additionally, a mild and versatile method based on copper-catalyzed [3 + 2] cycloaddition (Meldal–Sharpless reaction) was developed to tether quinolinones to O-atoms of 1,5- or 1,8-dinaphthols. The triazolo linkers could be considered as anti and syn products, which are interesting precursors for functionalized epidermal growth factor receptor (EGFR) inhibitors with potential apoptotic antiproliferative action. The antiproliferative activities of the 4a–e and 7a–e were evaluated. Compounds 4a–e and 7a–e demonstrated strong antiproliferative activity against the four tested cancer cell lines, with mean GI₅₀ ranging from 34 nM to 134 nM compared to the reference erlotinib, which had a GI₅₀ of 33 nM. The most potent derivatives as antiproliferative agents, compounds 4a, 4b, and 7d, were investigated for their efficacy as EGFR inhibitors, with IC₅₀ values ranging from 64 nM to 97 nM. Compounds 4a, 4b, and 7d demonstrated potent apoptotic effects via their effects on caspases 3, 8, 9, Cytochrome C, Bax, and Bcl2. Finally, docking studies show the relevance of the free amino group of the quinoline moiety for antiproliferative action via hydrogen bond formation with essential amino acids.

An efficient synthesis of a series of pyridazino[4,3-c:5,6-c′]diquinolines was achieved via the autoxidation of 4-hydrazinylquinolin-2(1H)-ones. IR, NMR (¹H and ¹³C), mass spectral data, and elemental analysis were used to fit and elucidate the structures of the newly synthesized compounds. X-ray structure analysis and theoretical calculations unequivocally proved the formation of the structure. The possible mechanism for the reaction is also discussed.