Triazolothiadiazole Derivatives Research Articles

Synthesis, antimicrobial and cytotoxicity studies of novel undecenoic acid-based triazolothiadiazole derivatives

In the present study, synthesis, antimicrobial and cytotoxic activity studies of 3,6-disubstituted-[1,2,4]triazolo [3,4-b][1,3,4]thiadiazole series compounds have been carried out. Compounds 6d , 6i , 6k , 6p , 6q , 6r , 6s and 6t exhibit promising activity with MIC value of 3.9 µg/mL against some of the tested bacterial strains. Compounds 6r and 6s consistently show promising minimum bactericidal concentration activity with MBC value of 7.8 µg/mL against Staphylococcus aureus MTCC 96 strain. Cytotoxic evaluation study claims that most of the compounds exhibit significant cytotoxicity against all the studied cancer cell lines. Particularly, compounds 6c , 6k , 6l , 6n and 6t against HeLa cell line and compounds 6c and 6h against B16-F10 cell line exhibit promising activities with IC 50 values ranging from 6.34 to 9.99 μM. Further, most of the compounds are non-toxic against Chinese hamster ovary cell (CHO-K1) normal cell.

Design, Synthesis and Biological Evaluation of Novel Triazolothiadiazoles Derived from NSAIDs as Anticancer Agents.

Although transplantation, surgical resection, and tumor ablation are treatment options available following early diagnosis of HCC, poor prognosis and high recurrence rates restrict the efficacy of these approaches. Hence, small molecules with high selectivity and bioactivity are urgently required. This study presents the synthesis of a series of new triazolothiadiazole derivatives (1a-3j) with NSAID moieties and their cytotoxic bioactivities. The new synthetic derivatives (1-3; 1a-3j) and NSAIDs ibuprofen, naproxen, and flurbiprofen that commonly used in clinics were screened against human liver (Huh7), breast (MCF7), and colon (HCT116) carcinoma cell lines under in vitro conditions via NCI-sulforhodamine B assay. The 4-methoxyphenyl substituted condensed derivatives 1h, 2h, and 3h were the most active compounds. Based on its high potency, compound 3h was selected for the further biological evaluation of hepatocellular carcinoma cell lines, and the mechanisms underlying cell death induced by 3h were determined. The results revealed that compound 3h induced apoptosis and cell cycle arrest in the sub G1 phase in human liver cancer cells. These new small molecules may be used for the development of new lead compounds.

In silico Investigation and Molecular Docking Study of Triazolo-thiadiazole Derivatives for Antimicrobial, Anti-inflammatory and Anti-diabetic Activity

Abstract: Triazolo-thiadiazole and connected fused ring in heterocyclic compounds are of highly interest in potential bioactive molecules. Triazolo-thiadiazole derivatives have lead of organic chemists due to their good biological and chemotherapeutic significance. Research in the field of anti-mycobacterium, anti-inflammatory, anti-diabetic and anti- microbial therapies are ongoing and studies are seeking. Therefore, the discovery of new effective anti-mycobacterium, anti-inflammatory, anti-diabetic and antimicrobial agents are imperative. Swiss programs are used to predict Triazolo-thiadiazole derivatives properties that are important for drug profile. Later, all of them were docked into the active sites of enzymes namely Ribosomal RNA large subunit methyltransferase (1P91), PeriplasmicOligopeptide-Binding Protein (1B05) and Protein-tyrosine phosphatase, non-receptor type 1 (1q6s), those were considered in Antidiabetic studies of triazolo- thiazazole derivative. Docking study when compared with Triazolo-thiadiazole derivatives with standard drug, derivative docking result is better. Ciprofloxacin, ibuprofen, and acarbose have been used as standard drugs for antimicrobial, anti-inflammatory and anti- diabetic activity in comparative docking studies. Key words: Triazolo-thiodizole, Antibacterial, Anti-diabetic, Antitubercular, Anti-inflammatory.

Anticancer Activity of Triazolo-Thiadiazole Derivatives and Inhibition of AKT1 and AKT2 Activation

The fusion of 1,2,4-triazole and 1,3,4-thiadiazole rings results in a class of heterocycles compounds with an extensive range of pharmacological properties. A series of 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles was synthesized and tested for its enzyme inhibition potential and anticancer activity. The results show that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles display potent anticancer properties in vitro against a panel of cancer cells and in vivo efficacy in HT-29 human colon tumor xenograft in CB17 severe combined immunodeficient (SCID) mice. Preliminary mechanistic studies revealed that KA25 and KA39 exhibit time- and concentration-dependent inhibition of Akt Ser-473 phosphorylation. Molecular modeling experiments indicated that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles bind well to the ATP binding site in Akt1 and Akt2. The low acute toxicity combined with in vitro and in vivo anticancer activity render triazolo[3,4-b]thiadiazoles KA25, KA26, and KA39 promising cancer therapeutic agents.

In vitro Anti-cancer Evaluation and Molecular Docking studies of Pyrazole substituted triazolo-thiadiazole derivatives

In vitro Anti-cancer Evaluation and Molecular Docking studies of Pyrazole substituted triazolo-thiadiazole derivatives

Microwave-assisted synthesis and pharmacological screening of some triazolothiadiazole derivatives

In this study, twenty-two new [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles (5a-n, 6a-h) were synthesized under microwave irradiation (MWI). The chemical structures of the compounds were elucidated by their IR, 1 H-NMR, LC-MS, and elemental analysis. The compounds were tested for antinociceptive activity by using the tail clip, tail flick, hot plate, and writhing methods in mice. The varying levels of antinociceptive activity of the compounds were compared with those of aspirin. Among these compounds, compound 5g and 5j were found to be significantly more active than the other compounds and the standard in the tests. Also, inhibitory effects of the test compounds on COX-1 and COX-2 activities were investigated. DuP-697 for COX-2 and SC-560 for COX-1 were used as reference standards.

Structural Modifications of the Triazolo-thiadiazole Derivatives as DOT1L Inhibitors and Their Activities

Structural Modifications of the Triazolo-thiadiazole Derivatives as DOT1L Inhibitors and Their Activities

Design, Synthesis, and Biological Activities of Novel Triazolothiadiazole Derivatives Linked with Amino Side Chain Containing Urea Group as DOT1L Inhibitors

Design, Synthesis, and Biological Activities of Novel Triazolothiadiazole Derivatives Linked with Amino Side Chain Containing Urea Group as DOT1L Inhibitors

Microwave-assisted synthesis of 3-substituted-6-ferrocene methylene-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles

A series of triazolo-thiadiazole derivatives containing ferrocene were synthesized under microwave assistance. Compared with the phosphorus oxychloride method, the microwave method has the advantages of simple operation, short reaction time, fast reaction rate and high yield. The effects of different reaction conditions were explored, and under the optimized conditions, the products were obtained in good yields (up to 80%).

Synthesis and biological activities of 3,6-disubstituted-1,2,4-triazolo-1,3,4- thiadiazole derivatives

Twelve novel triazolothiadiazole derivatives were synthesized from 4-amino-5-substituted-4H-1,2,4-triazole-3-thiols with various aromatic carboxylic acids by cyclization in the presence of phosphorous oxychloride. All the newly synthesized compounds were characterized by FTIR, 1H NMR, mass spectroscopy and elemental analysis. The antimicrobial activities of the title compounds were examined by disc diffusion method against Escherichia coli, Staphylococcus aureus, Pyricularia oryzae and Rhizoctnia solani. The bioassay indicated all synthesized triazolothiadiazole derivatives possessed moderate to good antibacterial and antifungal activities against the tested organisms. Especially, compounds 2e and 2k exhibited excellent antibacterial and antifungal activities among these triazolothiadiazole derivatives. KEY WORDS: Triazolothiadiazole, Triazole, Thiadiazole, Antimicrobial activity Bull. Chem. Soc. Ethiop. 2017, 31(3), 481-489.DOI: http://dx.doi.org/10.4314/bcse.v31i3.12

Synthesis and Cell Division Cycle 25B Phosphatase and Protein Ty-rosine Phosphatase 1B Inhibitory Activity Evaluation of Novel 3,6-Disubstituted Triazolothiadiazole Derivatives

Synthesis and Cell Division Cycle 25B Phosphatase and Protein Ty-rosine Phosphatase 1B Inhibitory Activity Evaluation of Novel 3,6-Disubstituted Triazolothiadiazole Derivatives

Investigations on Molecular Structure, Electronic Properties, NLO Properties and Comparison of Drug-Likeness of Triazolothiadiazole Derivatives by Quantum Methods and QSAR Analysis

Investigations on Molecular Structure, Electronic Properties, NLO Properties and Comparison of Drug-Likeness of Triazolothiadiazole Derivatives by Quantum Methods and QSAR Analysis

Exploiting the Role of Molecular Electrostatic Potential, Deformation Density, Topology, and Energetics in the Characterization of S···N and Cl···N Supramolecular Motifs in Crystalline Triazolothiadiazoles

A detailed analysis of the molecular and crystal packing of a series of pharmaceutically active triazolothiadiazole derivatives is reported. The most notable feature from the analysis of the supramolecular motifs is the presence of inversion dimers due to the formation of strong S···N chalcogen bonds. This has been unequivocally established via inputs from energy calculations from PIXEL, the topological analysis using the approach of QTAIM from AIMALL, an analysis of the molecular electrostatic potentials plotted on Hirshfeld surfaces, and the analysis of the 3D-deformation densities obtained using Crystal Explorer. The total interaction energy for this contact is in the range of 28–33 kJ/mol in the molecules under investigation, and the electrostatic (Coulombic + polarization) contribution toward the total stabilization energy is more than 70%, indicating that such interactions are principally electrostatic in origin. The results from the analysis of the molecular ESP depict that this interaction exists ...

Acetylcholinesterase inhibition activity of some quinolinyl substituted triazolothiadiazole derivatives

Acetylcholinesterase inhibition activity of some quinolinyl substituted triazolothiadiazole derivatives

Syntheses and Biological Activities of V-Shaped Symmetrical Triazolothiazine Oxadiazole Derivatives†

To build V-shaped symmetrical structure thiadiazole derivatives,isophthalic acid and 5-aminoisophthalic acid condensed with 3-aliphatic-1,2,4-triazole( 1) respectively. In POCl3 presence,fourteen symmetrical V-shaped triazolo-thiadiazole derivatives( 2a—2g and 3a—3g) were synthesized,wherein thirteen of them were first synthesized,and the structures of compounds 2 and 3 were characterized by infrared( IR),nuclear magnetic resonance( NMR) and high resolution mass spectrometer( HRMS). The inhibitory activities of the target compounds were screened for Cdc25 B and PTP1 B. The results showed that some compouds exhibited inhibitory activities against Cdc25 B,compounds 3b and 3f may be used as potential Cdc25 B inhibitors in the treatment of cancer. Compouds 3b—3g exhibited inhibitory activities against PTP1 B. Compounds 3b and 3e may be used as potential PTP1 B inhibitors in the treatment of diabetes.

Synthesis, characterization and photophysical properties of novel azole derivatives.

This paper concerns the design, synthesis, structural characterization, thermal stability evaluation and fluorescence properties of novel triazolothiadiazole derivatives. The target compounds 6a-e were synthesized by condensing 4-amino-3-(4-methoxybenzyl)-1H-1,2,4-triazole-5 (4H)-thione (5) with biphenyl, naphthyl, p-terphenyl, pyrenyl and ferrocenyl carboxylic acid in the presence of phosphorous oxychloride. The structures of newly synthesized compounds were characterized by IR, (1)H NMR and (13)C NMR analysis. The photophysical properties of synthesized compounds were measured in a variety of organic solvents of variable polarities. Spectral properties of the compounds were highly dependent on the nature of the substituent and coupling components attached to the triazolothiadiazole skeleton as well as slightly affected by the solvent polarities. Correlation of the absorption spectra and fluorescence emission response of 6a-e with the substituent revealed that the fluorescent properties can easily be tuned by varying conjugation length of side coupled groups. The newly synthesized derivatives represent a new type of fluorescent materials with efficient visible absorption and surpassing brightness which could be a promising candidate for bioimaging, photonic applications, organic light emitting diodes and dye sensitized solar cells.

ACETYLCHOLINESTERASE INHIBITION ACTIVITY OF SOME QUINOLINYL SUBSTITUTED TRIAZOLOTHIADIAZOLE DERIVATIVES.

A series of aralkanoic acids was converted into aralkanoic acid hydrazides through their esters formation. The aralkanoic acid hydrazides upon treatment with carbon disulfide and methanolic potassium hydroxide yielded potassium dithiocarbazinate salts, which on refluxing with aqueous hydrazine hydrate yielded 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles. The target compounds, 3-aralkyl-6-(substitutedquinolinyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, were synthesized by condensing various quinolinyl substituted carboxylic acids with 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles in phosphorus oxychloride. The structures of the newly synthesized triazolothiadiazoles were characterized by IR, 1H NMR, 13C NMR, and elemental analysis studies. The structure of one of the 5-aralkyl-4-amino-3-mercapto-1,2,4-triazoles was unambiguously deduced by single crystal X-ray diffraction analysis. All the synthesized compounds were screened for their acetylcholinesterase inhibition activities. Four of the triazolothiadiazoles exhibited excellent acetylcholinesterase inhibition activities as compared to the reference inhibitor.

ChemInform Abstract: Unprecedented Conversion of (Z)‐3‐Chloro‐3‐arylacrylic Acids to Benzoic Acids: Synthesis of s‐Triazolo[3,4‐b][1,3,4]thiadiazoles.

AbstractTreatment of 3‐arylacrylic acids with POCl3 results in the formation of benzoic acids which undergo in situ condensation with triazoles (II) to afford triazolothiadiazole derivatives.

ChemInform Abstract: Synthesis and Anticonvulsant Activities of Some Triazolothiadiazole Derivatives.

AbstractSynthesis and anticonvulsant activity of 6‐substituted [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazole derivatives (III) and (V) are described.

Synthesis and Anticonvulsant Activities of Some Triazolothiadiazole Derivatives

The present study describes the synthesis and anticonvulsant activity evaluation of 6-substituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (4a-4x) and their partially dehydrogenated products 5,6-dihydro-6-substituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (5a-5n). The bioevaluation demonstrated that most compounds in the series of 4a-4x exhibited potent anticonvulsant activity in the maximal electroshock test. Among which, 6-(4-chlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (4h) emerged as the most promising candidate on the basis of its favorable ED(50) value of 23.7 mg/kg and PI value of 10.8. In addition, the potency of compound 4h against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline in the chemical-induced seizure tests suggested that compound 4h displayed broad-spectrum activity in several models, and it may exert its anticonvulsant activity through affecting the GABAergic system.