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

• Published in: Acta crystallographica. Section C, Crystal structure communications Vol. 79; no. 9; pp. 334 - 343
• Main Authors: Nitek, Wojciech, Szymańska, Ewa, Tejchman, Waldemar, Żesławska, Ewa
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2023
• Subjects: Acetic acid; Binding; Butyric acid; Carboxyl group; Chemical bonds; Dimethyl sulfoxide; Efflux; Glycoproteins; Hydrogen bonds; Sulfoxides; crystal structure; hydrogen bonding; induced-fit docking; efflux pump inhibitor; 5-arylidenerhodanine derivatives
• ISSN: 0108-2701; 2053-2296; 1600-5759
• DOI: 10.1107/S2053229623006502

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 H NO S ·C H OS (1), 4-[5-([1,1'-biphenyl]-4-ylmethylidene]-4-oxo-2-thioxothiazolidin-3-yl)butanoic acid, C H NO S (2), 5-[4-(benzyloxy)benzylidene]-2-thioxothiazolidin-4-one, C H NO S (3), 4-{5-[4-(benzyloxy)benzylidene]-4-oxo-2-thioxothiazolidin-3-yl}butanoic acid, C H NO S (4), and 5-[4-(diphenylamino)benzylidene]-2-thioxothiazolidin-4-one, C H N OS (5). Compounds 1 and 3-5 crystallize in the triclinic space group P\overline 1, while 2 crystallizes in the monoclinic space group P2 /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.