The 1,3,4-thiadiazole nucleus is one of the most important and well-known heterocyclic nuclei, which is a common and integral feature of a variety of natural products and medicinal agents. Thiadiazole nucleus is present as a core structural component in an array of drug categories such as antimicrobial, anti-inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, and antitubercular agents. The broad and potent activity of thiadiazole and their derivatives has established them as pharmacologically significant scaffolds. In this study, an attempt has been made with recent research findings on this nucleus, to review the structural modifications on different thiadiazole derivatives for various pharmacological activities.
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http://dx.doi.org/10.1111/cbdd.12125 | DOI Listing |
Molecules
January 2025
Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
MDM2 and MDM4 are major negative regulators of tumor suppressor p53. Beyond regulating p53, MDM2 possesses p53-independent activity in promoting cell cycle progression and tumorigenesis via its RING domain ubiquitin E3 ligase activity. MDM2 and MDM4 form heterodimer polyubiquitin E3 ligases via their RING domain interaction.
View Article and Find Full Text PDFCommun Biol
January 2025
Obsidian Therapeutics, Cambridge, MA, USA.
Adoptive cell therapies (ACT) have shown reduced efficacy against solid tumor malignancies compared to hematologic malignancies, partly due to the immunosuppressive nature of the tumor microenvironment (TME). ACT efficacy may be enhanced with pleiotropic cytokines that remodel the TME; however, their expression needs to be tightly controlled to avoid systemic toxicities. Here we show T cells can be armored with membrane-bound cytokines with surface expression regulated using drug-responsive domains (DRDs) developed from the 260-amino acid protein human carbonic anhydrase 2 (CA2).
View Article and Find Full Text PDFJ Med Chem
January 2025
Shanghai Applied Radiation Institute, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, P. R. China.
The prevalence of drug-resistant bacteria is a major challenge throughout the world, especially with respect to Gram-negative bacteria, such as drug-resistant , which are regarded as the greatest bacterial threat to human health by the World Health Organization (WHO). In this work, 1,3,4-thiadiazole was introduced into the main skeleton of the classical peptidomimetic peptide deformylase (PDF) inhibitor in pursuit of highly efficient and broad-spectrum bacteriostatic drugs. Upon detailed structure-activity relationship study, PDF inhibitors that possess satisfactory activity against both Gram-positive and Gram-negative bacteria as well as a lower potential for methemoglobin toxicity were screened out.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
This study explores the design, synthesis, and evaluation of a novel series of isobenzofuran-based imidazo[2,1-b][1,3,4]thiadiazole derivatives, targeting their antimicrobial and anticancer properties. These compounds integrate the pharmacologically significant 1,3,4-thiadiazole and imidazole moieties, which are known for their potential in drug development, although imidazo[2,1-b][1,3,4]thiadiazole-based drugs are not yet available on the market. Therefore, the aim of this study is to develop novel derivatives that could serve as promising candidates for future therapeutic applications.
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December 2024
Department of Biophysics, Faculty of Environmental Biology, University of Life Sciences in Lublin, Akademicka 13, 20-950, Lublin, Poland.
We present a comprehensive spectroscopic study supported by theoretical quantum chemical calculations conducted on a molecular system (4-(5-methyl-1,3,4-thiadiazol-2-yl)benzene-1,3-diol (C1) and the antibiotic Amphotericin B (AmB)) that exhibits highly synergistic properties. We previously reported the strong synergism of this molecular system and now wish to present related stationary measurements of UV-Vis absorption, fluorescence, and fluorescence anisotropy in a polar, aprotic solvent (DMSO and a PBS buffer), followed by time-resolved fluorescence intensity and anisotropy decay studies using different ratios of the selected 1,3,4-thiadiazole derivative to Amphotericin B. Absorption spectra measured for the system revealed discrepancies in terms of the shapes of absorption bands, particularly in PBS.
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