Within the current challenges in medicinal chemistry, the development of new and better therapeutic agents effective against infectious diseases produced by bacteria, fungi, viruses, and parasites stands out. With chemotherapy as one of the main strategies against these diseases focusing on the administration of organic and inorganic drugs, the latter is generally based on the synergistic effect produced by the formation of metal complexes with biologically active organic compounds. In this sense, Schiff bases (SBs) represent and ideal ligand scaffold since they have demonstrated a broad spectrum of antitumor, antiviral, antimicrobial, and anti-inflammatory activities, among others. In addition, SBs are synthesized in an easy manner from one-step condensation reactions, being thus suitable for facile structural modifications, having the imine group as a coordination point found in most of their metal complexes, and promoting chelation when other donor atoms are three, four, or five bonds apart. However, despite the wide variety of metal complexes found in the literature using this type of ligands, only a handful of them include on their structures tridentate SBs ligands and their biological evaluation has been explored. Hence, this review summarizes the most important antimicrobial activity results reported this far for pincer-type complexes (main group and d-block) derived from SBs tridentate ligands.
Fluorination of pharmaceutical agents has afforded crucial modifications to their pharmacological profiles, leading to important advances in medicinal chemistry. On the other hand, metallodrugs are considered to be valuable candidates in the treatment of several diseases, albeit with the caveat that they may exhibit pharmacological disadvantages, such as poor water solubility, low bioavailability and short circulating time. To surmount these limitations, two approaches have been developed: one based on the design of novel metallodrug-delivering carriers and the other based on optimizing the structure of the ligands bound to the metal center. In this context, fluorination of the ligands may bring beneficial changes (physicochemical and biological) that can help to elude the aforementioned drawbacks. Thus, in this review, we discuss the use of fluorinated ligands in the design of metallodrugs that may exhibit potential anticancer activity.
16 February 2021 in PLOS Neglected Tropical Diseases
Identifying the Mycobacterium tuberculosis resistance mutation patterns is of the utmost importance to assure proper patient’s management and devising of control programs aimed to limit spread of disease. Zoonotic Mycobacterium bovis infection still represents a threat to human health, particularly in dairy production regions. Routinary, molecular characterization of M. bovis is performed primarily by spoligotyping and mycobacterial interspersed repetitive units (MIRU) while next generation sequencing (NGS) approaches are often performed by reference laboratories. However, spoligotyping and MIRU methodologies lack the resolution required for the fine characterization of tuberculosis isolates, particularly in outbreak settings. In conjunction with sophisticated bioinformatic algorithms, whole genome sequencing (WGS) analysis is becoming the method of choice for advanced genetic characterization of tuberculosis isolates. WGS provides valuable information on drug resistance and compensatory mutations that other technologies cannot assess. Here, we performed an analysis of the most frequently identified mutations associated with tuberculosis drug resistance and their genetic relationship among 2,074 Mycobacterium bovis WGS recovered primarily from non-human hosts. Full-length gene sequences harboring drug resistant associated mutations and their phylogenetic relationships were analyzed. The results showed that M. bovis isolates harbor mutations conferring resistance to both first- and second-line antibiotics. Mutations conferring resistance for isoniazid, fluoroquinolones, streptomycin, and aminoglycosides were identified among animal strains. Our findings highlight the importance of molecular surveillance to monitor the emergence of mutations associated with multi and extensive drug resistance in livestock and other non-human mammals.
1 March 2008 in Current Topics in Medicinal Chemistry
This review focuses in the role that antioxidant enzymes play in protection and other important physiological functions such as signal transduction, cell differentiation, growth and apoptosis. Parasites use these enzymes to evade ROS produced by the host immune response and for development inside the host. In the cestoda Taenia solium, three antioxidant enzymes have been studied: a cystosolic Cu,Zn superoxide dismutase that is a target of cestocidal drugs (bencimidazoles); a 2-Cys peroxiredoxin that is a regulatory enzyme of H2O2, molecule essential for several physiological functions; and two isoforms of glutathione transferases that are immunological targets, since they protect immunized mice against cysticercosis. Moreover, all these enzymes are present in all stages of the parasite. These findings suggest that antioxidant enzymes have an important role in T. solium physiology and infection, therefore they might represent the Achilles heel of the parasite.