STRUCTURAL ANALYSIS OF TWISTED AMIDES BASED ON THE SPIROHYDANTOIN SCAFFOLD WITH THE ANTICANCER ACTIVITY

Abstract

Five spirohydantoin derivatives were synthesized and analyzed by single crystal X-ray diffraction and DFT calculations (Figure 1). Compounds 1–3 and 5 crystallize as a syn conformation with respect to the ureic part (N1–C2(=O)–N3) of the hydanoin moiety, while compound 4 crystallize as an anti conformation. All compounds feature a distorted exocyclic amide bond that results from the twisting and pyramidalization of the N3 atom (Figure 2). Compound 2 with τ = 86.9° (97% of theoretical maximum) contains one of the most twisted amide bonds reported so far. The anticancer effects of the investigated compounds were evaluated against selected human cancer cell lines, as well as human normal lung fibroblasts (MRC5) cell lines. It appears that moderately distorted twisted amides with highly lipophilic substituents are the most potent within the series.