Architecture of the rings of 5-arylidenerhodanine derivatives versus P-gp inhibition.

5-Arylidene derivatives of rhodanine show various biological activities. The new crystal structures of five derivatives investigated towards ABCB1 efflux pump modulation are reported, namely, 2-[5-([1,1'-biphenyl]-4-ylmethylidene]-4-oxo-2-thioxothiazolidin-3-yl)acetic acid dimethyl sulfoxide monosolvate, C 18 H 13 NO 3 S 2 ·C 2 H 6 OS (1), 4-[5-([1,1'-biphenyl]-4-ylmethylidene]-4-oxo-2-thioxothiazolidin-3-yl)butanoic acid, C 20 H 17 NO 3 S 2 (2), 5-[4-(benzyloxy)benzylidene]-2-thioxothiazolidin-4-one, C 17 H 13 NO 2 S 2 (3), 4-{5-[4-(benzyloxy)benzylidene]-4-oxo-2-thioxothiazolidin-3-yl}butanoic acid, C 21 H 19 NO 4 S 2 (4), and 5-[4-(diphenylamino)benzylidene]-2-thioxothiazolidin-4-one, C 22 H 16 N 2 OS 2 (5). Compounds 1 and 3-5 crystallize in the triclinic space group P\overline 1, while 2 crystallizes in the monoclinic space group P2 1 /n, where the biphenyl moiety is observed in two positions (A and B). Two molecules are present in the asymmetric unit of 5 and, for the other four compounds, there is only one molecule; moreover, 1 crystallizes with one dimethyl sulfoxide molecule. The packing of the molecules containing a carboxyl group (1, 2 and 4) is determined by O-H...O hydrogen bonds, while in the other two compounds (3 and 5), the packing is determined by N-H...O hydrogen bonds. Additionally, induced-fit docking studies have been performed for the active compounds to investigate their putative binding mode inside the human glycoprotein P (P-gp) binding pocket.