The Azoles in Pharmacochemistry: Perspectives on the Synthesis of New Compounds and Chemoinformatic Contributions

Abstract

: Due to their versatile biological activity, Azoles are widely studied in pharmacochemistry. It is possible to use them in many applications and in studies aimed at discovering antiparasitic, antineoplastic, antiviral, antimicrobial compounds; and in the production of materials for treatment of varied pathologies. Based on their biological activity, our review presents several studies that involve this class of organic compounds. A bibliographic survey of this type can effectively contribute to pharmaceutical sciences, stimulating the discovery of new compounds, and structural improvements to biological profiles of interest. In this review, articles are discussed involving the synthesis of new compounds and chemoinformatic contributions. Current applications of azoles in both the pharmaceutical and agri-business sectors are well known, yet as this research highlights, azole compounds can also bring important contributions to the fight against many diseases. Among the heterocyclics, azoles are increasingly studied by research groups around the world for application against tuberculosis, HIV, fungal and bacterial infections; and against parasites such as leishmaniasis and trypanosomiasis. Our hope is that this work will help arouse the interest of research groups planning to develop new bioactives to fight against these and other diseases.

Stereoselective Synthesis and Application of Gibberellic Acid-Derived Aminodiols

“…As azoles are known to be endowed with a variety of biological activities [ 41 ], we have tried to perform the azole-mediated ring-opening of 3 with a variety of azoles ( Table 2 ). Likewise amines, the oxirane ring could only be opened in the presence of K 2 CO 3 owing to the lower reactivity of N -containing heterocycles.…”

Evaluation and discovery of novel benzothiazole derivatives as promising hits against Leishmania infantum

“…Therefore, important research efforts from public organizations (DNDi, 2023b), pharmaceutical companies (Peña et al., 2015) and academic research groups (Cassiano Martinho et al., 2022; Ferreira et al., 2021; Jacques Dit Lapierre et al., 2023; Koovits, Dessoy, Matheeussen, Maes, Caljon, Ferreira, et al., 2020; Lal et al., 2023; McNamara et al., 2022) have been performed over the last decades, in order to identify clinical candidates which might overcome the shortcomings of the current treatments (Chatelain, 2015; Field et al., 2017; Koovits, Dessoy, Matheeussen, Maes, Caljon, Mowbray, et al., 2020). Among the resulting literature from such works, benzothiazole‐containing compounds can be encountered in numerous studies targeting diverse parasites, in which the inclusion of a benzothiazole fragment provides compounds active against Trypanosoma brucei (Berg et al., 2001; Brown et al., 2020; de Oliveira Viana et al., 2019; Linciano et al., 2019), T. cruzi (Berg et al., 2001; Cuevas‐Hernández et al., 2020; Fleau et al., 2019; Martínez‐Cerón et al., 2021), L. infantum (de Oliveira Viana et al., 2019), Plasmodium falciparum (Berg et al., 2001), and Cryptosporidium parvum (Oboh et al., 2023), among others. Thus, we selected as initial hit for this work the acylaminobenzothiazole 1 , of which the antitrypanosomal activity was identified in a primary HTS screening of the NIH compound collection against T. cruzi performed by the Broad Institute (bioassay number AID 1885) (P. B.…”

2-(Nitroaryl)-5-Substituted-1,3,4-Thiadiazole Derivatives with Antiprotozoal Activities: In Vitro and In Vivo Study

“…Natural and synthetic heterocyclic compounds, particularly the azole heterocycles, showed antiprotozoal activity [ 15 , 16 ]. Due to the straightforward synthetic approaches and easy ring functionalization, such scaffolds attract attention in the design of trypanocidal agents [ 17 , 18 ]. Antifungal azoles, such as posaconazole and ravuconazole, were repositioned as potential anti-trypanosomal agents in recent years.…”