Antimicrobial resistance is an increasing problem for the global public health. One of the strategies to combat this issue is the synthesis of novel antimicrobials through rational drug design based on extensive structure-activity relationship studies. The thiazole nucleus is a prominent feature in the structure of many authorized antimicrobials, being clubbed with different heterocycles. The purpose of this review is to study the structure-activity relationship in antimicrobial thiazoles clubbed with various heterocycles reported in the literature between 2017 and 2022, in order to offer an overview of the last years in terms of antimicrobial research and provide a helpful instrument for future research in the field.

We have recently reported that a series of 1,3,4-oxadiazol-2-ylbenzenesulfonamides acts as potent and specific monoamine oxidase B (MAO-B) inhibitors with some compounds possessing potencies in the nanomolar range. While sulfonamide compounds (e.g., zonisamide) have been reported to inhibit the MAO enzymes, nanomolar MAO inhibition potencies for this class are not frequently observed. The present study expanded on these findings by replacing the 1,3,4-oxazole moiety with a 1,3-thiazole heterocycle. A series of 23 primary sulfonamides were synthesized by reaction of an α-haloketone with a substituted carbothioamide. The results of the MAO inhibition studies showed that the 1,3-thiazolylbenzenesulfonamides were specific inhibitors of human MAO-B. The most potent MAO-B inhibitor exhibited an in vitro IC50 value of 0.103 µM (3j). The derivatives were, however, weaker inhibitors of human MAO-A with the most potent compound exhibiting an IC50 value of 11.9 µM (3a). Examination of the structure-activity relationships (SARs) showed that the most potent MAO-B inhibition was obtained with substitution of the sulfonamide on the meta position of the phenyl rather than the para position. This study concludes that 1,3-thiazolylbenzenesulfonamides represent a class of potent and specific MAO-B inhibitors, which may serve as leads for the development of new treatments for disease states such as Parkinson’s disease.

The purpose of our work was the search for safe and effective biologically active substances of cardiotropic action among 1,3- thiazole derivatives. New derivatives of 1-[(2Z)-2-[R-imin]-4-methyl-3-R¹-2,3-dihydro-1,3-thiazole-5-yl]ethan-1-one and ethyl-(2Z)-2-[R-imin]-4-methyl-3-R¹-2,3-dihydro-1,3-thiazole-5-carboxylate were synthesized by the Hantzsch reaction. The structure of the compounds obtained was confirmed by ¹H NMR spectroscopy and by the elemental analysis. The pharmacological screening showed that the obtained substances possess cardiotropic activity. The cardiotropic properties of the new 1,3-thiazole derivatives were studied on the isolated rings of the thoracic aorta of laboratory rats. A prospective substance 1-[(2Z)-2-[(4-methoxyphenyl)imin]-4-methyl-3-(4-methylpiperazin-1-yl) -2,3-dihydro-1,3-thiazol-5-yl]ethan-1-one hydrochloride, which exhibits cardiotropic activity exceeding the activity of L-carnitine and meldonia has been revealed during pharmacological researches of the substances obtained.

Stabilization of a G-quadruplex (G4) in the promotor of the c-MYC proto-oncogene leads to inhibition of gene expression, and it thus represents a potentially attractive new strategy for cancer treatment. However, most G4 stabilizers show little selectivity among the many G4s present in the cellular complement of DNA and RNA. Intriguingly, a crescent-shaped cell-penetrating thiazole peptide, TH3, preferentially stabilizes the c-MYC G4 over other promotor G4s, but the mechanisms leading to this selective binding remain obscure. To investigate these mechanisms at the atomic level, we performed an in silico comparative investigation of the binding of TH3 and its analogue TH1 to the G4s from the promotors of c-MYC, c-KIT1, c-KIT2, and BCL2. Molecular docking and molecular dynamics simulations, combined with in-depth analyses of non-covalent interactions and bulk and per-nucleotide binding free energies, revealed that both TH3 and TH1 can induce the formation of a sandwich-like framework through stacking with both the top and bottom G-tetrads of the c-MYC G4 and the adjacent terminal capping nucleotides. This framework produces enhanced binding affinities for the c-MYC G4 relative to other promotor G4s, with TH3 exhibiting an outstanding binding priority. Van der Waals interactions were identified to be the key factor in complex formation in all cases. Collectively, our findings fully agree with available experimental data. Therefore, the identified mechanisms leading to specific binding of TH3 towards the c-MYC G4 provide valuable information to guide the development of new selective G4 stabilizers.

The synthesis and structure of the 4,4′-dipyridyl N,N′-donor ligand with a central thiazolo[5,4-d]thiazole (tztz) unit, named Dptztz is presented. With the linker Dptztz and isophthalate (benzene-1,3-dicarboxylate, 1,3-BDC²⁻) the mixed-linker, two-dimensional coordination network [Zn(1,3-BDC)Dptztz]·DMF could be obtained (DMF = dimethylformamide), which belongs to the class of coordination polymers with interdigitated structures (CIDs). The incorporated DMF solvent molecules can be removed through solvent exchange and evacuation such that the supramolecular 3D packing of the 2D networks retains porosity for CO₂ adsorption in activated [Zn(1,3-BDC)Dptztz]. The first sorption study of a tztz-functionalized porous metal-organic framework material yields a BET surface of 417 m²/g from CO₂ adsorption. The heat of adsorption for CO₂ exhibits a relative maximum with 27.7 kJ/mol at adsorbed CO₂ of about 4 cm³/g STP which is interpreted as a gate-opening effect.

The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4'-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies a focused library of 23 halide-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB, and [3H]DCVJ. The DABTAs gave an overall chemical yield of 15 – 71%, with a calculated lipophilicity of 2.5 – 5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1 – 4.9 nM and up to 20 – 3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in-silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo and translational research and for further in vitro experiments on human-derived protein aggregates.

Leishmaniasis remains a significant global health concern, with current treatments relying on outdated drugs associated with high toxicity, lengthy administration, elevated costs, and drug resistance. Consequently, the urgent need for safer and more effective therapeutic options in leishmaniasis treatment persists. Previous research has highlighted selenium compounds as promising candidates for innovative leishmaniasis therapy. In light of this, a library of 10 selenium-containing diverse compounds was designed and evaluated in this study. The compounds were subjected to screening against L. amazonensis promastigotes, and their cytotoxicity was assessed in NIH/3T3 cells. Among the tested compounds, MRK-106 and MRK-108 displayed the highest potency against L. amazonensis promastigotes while demonstrating reduced cytotoxicity. Notably, MRK-106 and MRK-108 exhibited IC50 values of 3.97 µM, 4.23 µM, respectively, and most of the tested compounds showed low cytotoxicity in NIH/3T3 cells (CC50 > 200 µM). Although these results are promising, additional investigations focusing on intracellular amastigotes are required to determine the antileishmanial activity of the compounds. In conclusion, the identified selenium-containing compounds hold considerable potential as antileishmanial drug candidates and warrant further exploration in subsequent studies. These findings represent a significant step towards the development of safer and more effective therapies for leishmaniasis, addressing the pressing need for novel and improved treatments.