Abstract
AbstractImidazolidine-2-thione substructure represents a pharmaceutically attractive scaffold, being included in different antimicrobial, anticancer and pesticide agents. To further evaluate the pharmaceutical potential of this chemical moiety, imidazolidine-2-thione was reacted with atypical Vilsmeier adducts, obtained by the condensation between dimethylacetamide and various acyl chlorides endowed with different electronic and steric properties. The formation of mono-acylated or di-acylated thiourea derivatives emerged to be affected by the nature of the considered acyl chloride reagent. Computational semi-empirical simulations were carried out to rationalize the relevant factor influencing the outcome of the reaction. As acylthioureas are pharmacologically relevant compounds, the chemical versatility of mono-acylated derivatives were evaluated by reacting benzoyl imidazolidin-2-thione with acyl chlorides. A small library of asymmetric di-acylthioureas was prepared and the obtained derivatives did not show any cytotoxicity on SKOV-3 and MCF-7 cancer cell lines. Additionally, in silico studies predicted good pharmacokinetics properties and promising drug-like characteristics for mono- and di-acylated thioureas. These considerations further support the value of the prepared compounds as interesting non-cytotoxic chemical scaffold useful in the medicinal chemistry field.
Graphical abstract
Funder
Università degli Studi di Genova
Ministero della Salute
Publisher
Springer Science and Business Media LLC
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Drug Discovery,Molecular Biology,General Medicine,Information Systems,Catalysis
Reference35 articles.
1. Sun C, Huang H, Feng M, Shi X, Zhang X, Zhou P (2006) A novel class of potent influenza virus inhibitors: polysubstituted acylthiourea and its fused heterocycle derivatives. Bioorg Med Chem Lett 16:162–166. https://doi.org/10.1016/j.bmcl.2005.09.033
2. Saeed A, Batool M (2008) Synthesis and bioactivity of some new 1-tolyl-3-aryl-4-methylimidazole-2-thionesMed. Chem Res 16:143–154. https://doi.org/10.1007/s00044-007-9017-8
3. Toldy L, Solyom S, Kocka I, Toth G, Toth I (1971) Thiourea derivatives with tuberculostatic action. II. Acylthiocarbamides. Acta Chim Acad Sci Hung 69:221–227
4. Plutín AM, Alvarez A, Mocelo R, Ramos R, Castellano EE, da Silva MM, Villarreal W, Pavan FR, Meira C, Rodrigues FJS, Moreira DR, Soares MB, Batista AA (2017) Antitumor activity of Pd(II) complexes with N, S or O, S coordination modes of acylthiourea ligands. Polyhedron 132:70. https://doi.org/10.1016/j.poly.2020.114543
5. Misra VS, Pandey RN, Dua PR (1979) Synthesis of N-aryl-N’-[2-phenyl-3-quinazolino(3H)-4-one] acylthiourea derivatives as anticonvulsants. Pol J Pharmacol Pharm 31:161–167