Thioureas are widely used as intermediates in organic synthesis, and it is commonly used in several classes of heterocycles. There has been an escalating interest in the development of heterocyclic employing thioureas as building blocks. Furthermore, thioureas can be utilized as reagent in a synthesis of a large number of therapeutic agents. In addition, substituted thioureas have recently gained much interest in the preparation of wide variety of biologically active compounds. This review highlights the status of thiourea scaffold in the drug development and heterocyclic synthesis described in the literature since 2010.

An original and focused library of two sets of dihydropyrimidin-2-thiones (DHPMs) substituted with N-1 aryl groups derived from monastrol was designed and synthesized in order to discover a more effective Eg5 ligand than the template. Based on molecular docking studies, four ligands were selected to perform pharmacological investigations against two glioma cell lines. The results led to the discovery of two original compounds, called 20h and 20e, with an anti-proliferative effects, achieving IC₅₀ values of about half that of the IC₅₀ of monastrol in both cell lines. As with monastrol, flow cytometry analyses showed that the 20e and 20h compounds induced cell cycle arrest in the G₂/M phase, and immunocytochemistry essays revealed the formation of monopolar spindles due to Eg5 inhibition without any toxicity to Caenorhabditis elegans.

The discovery of a new drug requires over a billion dollars and around 12 years of research efforts, and toxicity is the leading reason for the failure to approve candidate drugs. Many alternative methods have been validated to detect toxicity as early as possible to diminish the waste of resources and efforts in medicinal chemistry research, and in vivo alternative methods are especially valuable for the amount of information they can provide at little cost and in a short time. In this work, we present a review of the literature published between the years 2000 and 2021 on in vivo alternative methods of toxicity screening employed in medicinal chemistry, which we believe will be useful because, in addition to shortening the research time, these studies provide much additional information aside from the toxicity of drug candidate compounds. These in vivo models include zebrafish, Artemia salina, Galleria mellonella, Drosophila melanogaster, planarians, and Caenorhabditis elegans. The most published ones in the last decade were zebrafish, D. melanogaster, and C. elegans due to their reliability, ease, and cost-effectiveness in implementation and flexibility. Special attention is given to C. elegans because of its rising popularity, a wide range of uses, including toxicity screening, and active effects measurement, from antioxidant effects to anthelmintic and antimicrobial activities, and its fast and reliable results. Over time, C. elegans also became a viable high-throughput (HTS) automated drug screening option. Additionally, this manuscript lists briefly the other screening methods used for the initial toxicological analyses and the role of alternative in vivo methods in these scenarios, classifying them as in silico, in vitro and alternative in vivo models that have been receiving a growing increase in interest in recent years.