Synthesis and Structure of Novel Hybrid Compounds Containing Phthalazin-1(2H)-imine and 4,5-Dihydro-1H-imidazole Cores and Their Sulfonyl Derivatives with Potential Biological Activities

A novel hybrid compound-2-(4,5-dihydro-1<i>H</i>-imidazol-2-yl)phthalazin-1(2<i>H</i>)-imine (<b>5</b>) was synthesized and converted into di-substituted sulfonamide derivatives <b>6a</b>-<b>o</b> and phthalazine ring opening products-hydrazonomethylbenzonitriles <b>7a</b>-<b>m</b>. The newly prepared compounds were characterized using elemental analyses, IR and NMR spectroscopy, as well as mass spectrometry. Single crystal X-ray diffraction data were collected for the representative compounds <b>5</b>, <b>6c</b>, <b>6e</b>, <b>7g</b>, and <b>7k</b>. The antiproliferative activity of compound <b>5</b>, sulfonyl derivatives <b>6a</b>-<b>o</b> and benzonitriles <b>7a</b>-<b>m</b> was evaluated on approximately sixty cell lines within nine tumor-type subpanels, including leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate, and breast. None of the tested compounds showed any activity against the cancer cell lines used. The antioxidant properties of all compounds were assessed using the DPPH, ABTS, and FRAP radical scavenging methods, as well as the β-carotene bleaching test. Antiradical tests revealed that among the investigated compounds, a moderate ABTS antiradical effect was observed for sulfonamide <b>6j</b> (IC₅₀ = 52.77 µg/mL). Benzonitrile <b>7i</b> bearing two chlorine atoms on a phenyl ring system showed activity in a β-carotene bleaching test (IC₅₀ = 86.21 µg/mL). Finally, the interaction AGE/RAGE in the presence of the selected phthalazinimines <b>6a</b>, <b>6b</b>, <b>6g</b>, <b>6m</b>, and hydrazonomethylbenzonitriles <b>7a</b>, <b>7c</b>-<b>g</b>, and <b>7i</b>-<b>k</b> was determined by ELISA assay. A moderate inhibitory potency toward RAGE was found for hydrazonomethylbenzonitriles-<b>7d</b> with an electron-donating methoxy group (R = 3-CH₃O-C₆H₄) and <b>7f</b>, <b>7k</b> with an electron-withdrawing substituent (<b>7f</b>, R = 2-Cl-C₆H₄; <b>7k</b>, R = 4-NO₂-C₆H₄).