A series of N-(5-(alkylthio)-1,3,4-thiadiazol-2-yl)acetamides and their 2-chloro analogues were synthesized via the acylation of 2-alkylthio-5-amino-1,3,4-thiadiazoles using acetyl chloride and chloroacetyl chloride. Structural characterization was performed using spectroscopic methods, with selected derivatives further confirmed by single-crystal X-ray analysis. The in vitro cytotoxic activity of the synthesized compounds was evaluated against a panel of cancer cell lines (CCRF-CEM, HEp-2, HeLa, and HBL-100) and normal cells. While the parent compounds and acetyl derivatives exhibited negligible activity, the chloroacetyl-substituted derivatives showed significantly enhanced cytotoxicity. The most potent derivatives demonstrated IC50 values of approximately 10 μM against CCRF-CEM cells, comparable to the reference drug cytarabine. However, the compounds displayed low selectivity toward cancer cells over normal cell lines. These results indicate that the incorporation of a chloroacetyl moiety is critical for increasing the cytotoxic potency, although its high reactivity may reduce therapeutic selectivity. Therefore, further structural optimization is required to improve selectivity and therapeutic potential.

In this work, the synthesis of 6,6'-([2,2'-bi(1,3,4-oxadiazole)]-5,5'-diyl)bis(3-chloroaniline) (6a) and 5,5'-([2,2'-bi(1,3,4-oxadiazole)]-5,5'-diyl)bis(benzene-1,3-diamine) (6b) was carried out and characterized by spectral data from 1H NMR, ¹³C NMR, IR and mass spectrometry. The optical properties of these compounds were studied, in particular the evolution of reflectance, absorption and band gap energy, and a scanning electron microscopy (SEM) analysis was performed. A comparative in-silico study combining DFT-based reactivity analysis, ADMET prediction, and molecular docking were employed for compounds 6a and 6b. Both exhibited distinct reactivity profiles and strong binding affinities toward DNA Gyrase B (7C7N) and the DNA-ruthenium complex (4E7Y), highlighting their potential as antibacterial agents, as well their potential use in photovoltaic application and for near infrared light shielding basing on the optical results.

This study presents the synthesis and characterization of the novel compound 6,6'-(1,3,4-oxadiazole-2,5-diyl)bis(3-chloroaniline), using 1H NMR, 13C NMR, mass spectrometry and FTIR-ATR infrared spectroscopy. Density Functional Theory (DFT) calculations at the B3LYP/6-311G (d,p) level, were employed to optimize the molecular geometry and evaluate electronic properties. Frontier molecular orbital, molecular electrostatic potential, Parr function, and electron localization function analyses revealed an ambiphilic character, with electrophilic sites localized on the oxadiazole core and nucleophilic regions on the chloroaniline moieties. Molecular docking demonstrated high binding affinities toward Topoisomerase IV, Tubulin, and CDK2, surpassing standard ligands and indicating potential antibacterial and anticancer activities. ADME/Toxicity predictions suggested good pharmacokinetic behavior and low toxicity. Monte Carlo and molecular dynamics simulations confirmed strong and stable adsorption of the novel compound OBA on the Fe (110) surface, supporting its efficiency as a corrosion inhibitor.

Some new 2-(2H-chromen-3-yl)-[1,3,4]oxadiazole derivatives 8a-e using Huisgen synthesis of 1,3,4-oxadiazoles reaction. Their structures were verified by 1H NMR and and elemental analyses. Compounds 8a-e were tested against 60 human cancer cell lines for in vitro cytotoxic activities according to the international scientific programme of the US National Institute of Health – DTP (Developmental Therapeutics Program), National Cancer Institute (Bethesda, Maryland, USA). Compounds with moderate activity against certain cancer cell lines were identified. In addition, in collaboration with CO-ADD (The Community for Open Antimicrobial Drug Discovery), we have studied the antibacterial activity against the ESCAPE group of strains and the antifungal activity against C. Albicans ATCC 90028 and C. Neoformans ATCC 208821. The studies allowed us to identify 3-[5-(6-bromo-2H-chromen-3-yl)-[1,3,4]oxadiazol-2-yl]-pyridine as a compound with high antibacterial activity against E. Coli ATCC 25922 with MIC 8 μg/ml. Docking studies have shown high affinity of this compound for the bacterial DNA gyrase of Escherichia coli.

This study presents the synthesis and characterization of the compound 5,5'-(methylenebis(1,3,4-oxadiazole-5,2-diyl))bis(benzene-1,3-diamine), by ¹H NMR, ¹³C NMR and FTIR-ATR infrared spectroscopy and mass spectrometry. A theoretical study was carried out by a comprehensive and hierarchical methodology in order to evaluate the inhibitory behavior of the molecule 5,5'-(methylenebis(1,3,4-oxadiazole-5,2-diyl))bis(benzene-1,3-diamine) with respect to the corrosion of a Fe(110) type metal surface. Thus, examination of non-covalent interactions by NCI analysis. In addition, the study of adsorption on the metal surface was carried out by the Monte Carlo method.

This study presents the synthesis and characterization of a novel 1,3,4-oxadiazole derivative compound, 2,5-bis(2-(trifluoromethyl)-1H-benzimidazol-5-yl)-1,3,4-oxadiazole, using ¹H NMR, ¹³C NMR, mass spectrometry and FTIR-ATR infrared spectroscopy. Reactivity, ADME/toxicity and docking to therapeutic targets were investigated revealed that 2,5-bis(2-(trifluoromethyl)-1H-benzimidazol-5-yl)-1,3,4-oxadiazole (BTBO) exhibits excellent intestinal absorption, limited solubility and CNS penetration, and restained clearance. It interacts with key cytochromes and transporters, suggesting possible drug–drug interactions. Toxicity evaluations indicated mutagenic potential and moderate oral toxicity, with no hepatotoxicity or skin sensitization. Molecular docking demonstrated strong binding affinities to targets in six therapeutic areas, often outshining reference ligands, supporting its auspicious pharmacokinetic and therapeutic potential.

Triazolo[3,4-b][1,3,4]thiadiazole molecules are found to be important tools in modern bioorganic and medicinal chemistry. This condensed system successfully combines two pharmacologically significant five-membered heterocycles – 1,2,4-triazole and 1,3,4-thiadiazole, which causes much more interest in the enhanced activity profile of its analogs than their parent separate constituents. It’s considered that the triazoles fused to thiadiazoles exhibit various therapeutically important properties, probably due to the existence of N-C-S fragments in their structures. In this review, we presented the summarized literature data about the diversity of pharmacological effects of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole based compounds as promising objects for the rational design of drug-like molecules.

Triazolo[3,4-b]thiadiazoles are a class of heterocyclic compounds, which have attracted great interest in medicinal chemistry owing to their wide range of pharmacological activities. A number of triazoles fused to thiadiazoles are incorporated into a wide variety of therapeutically important compounds possessing a broad spectrum of biological activities. Considering such a significant pharmacological potential, as well as wide synthetic possibilities triazolo-thiadiazoles have received considerable attention from scientific community and are extensively used for construction of prospective drug-likes molecules. In this review, we summarized the literature data about the main synthetic approaches for obtaining condensed heterocyclic compounds based on triazolo[3,4-b][1,3,4]thiadiazole scaffold as promising objects for modern bioorganic and medicinal chemistry.

A series of new 4-(1,3,4-thiadiazol-2-yl)-containing polysubstituted pyrroles 3 a-k has been synthesized by a preparative convenient method from ethyl 5-chloro-4-formyl-1H-pyrrole-3-carboxylates 1 a-e, which were selectively transformed into the corresponding polysubstituted pyrrole-4-carboxylic acids 2 а-е using sodium hypochlorite as an oxidizer. Further, they were transformed into the target compounds with a high yield using the cyclocondensation with N-mono- or N,N-disubstituted thiosemicarbazides in the boiling phosphorus trichloroxide. As seen from the screening of antimicrobial activity, the synthesized compounds exhibit the inhibiting and bactericide activity against some bacteria and fungi. The highest activity has been established for the compounds 3 a, c, e-h, j against the strain Klebsiella pneumoniae (МІС=31.25 µg/mL). The calculated HOMO energy level proves that the compound 3 с is the most reactive ligand for the interaction with a protein receptor. The molecular docking data show that the compound 3 h has the highest affinity to the ThiM Klebsiella pneumoniae kinase.

3-aryl-6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines were obtained with good yields (81-95%) via the heterocyclization reaction of 1-phenyl-2-((5-aryl-1,3,4-oxadiazole-2-yl)thio)ethane-1-ones in acetic acid. The physicochemical characteristics of the synthesized compounds were established, the structures were confirmed by the data of IR, ¹H and ¹³C NMR spectra, as well as the results of X-ray diffraction analysis. The cytotoxic, antibacterial and antifungal properties of these compounds were evaluated. In vitro screening results showed that compounds 8, 9 and 12 significantly inhibit (54-65%) the growth of HeLa, HBL-100 and CCRF-CEM cancer cell lines. It was found that the cytotoxicity of the synthesized compounds increases in the series of oxadiazoltiones (1-4) - S-derivatives (5-8) - triazolothiadiazines (9-12). Compounds 5-16 do not exhibit antimicrobial properties.