4-thiadiazole Derivatives Research Articles

Synthesis, in silico and in vitro Evaluation of 1, 3, 4-Thiadiazole Derivatives Fused with Biphenyl Compound

Synthesis, in silico and in vitro Evaluation of 1, 3, 4-Thiadiazole Derivatives Fused with Biphenyl Compound

Utilization of Computational Tools for the Discovery of Schiff Base-based 1, 3, 4-thiadiazole Scaffold as SGLT2 Inhibitors

Background:: High or abnormal blood sugar levels are the hallmark of diabetes mellitus (DM), a metabolic disorder that will be one of the major causes of mortality in 2021. SGLT2 inhibitors have recently shown beneficial effects in the treatment of diabetes by reducing hyperglycemia and glucosuria. Objective:: Molecular docking and ADMET studies of Schiff base- based 1, 3, 4-thiadiazole scaffold as SGLT2 inhibitors. Methods:: Chem draw Ultra 16.0 software was used to draw the structures of newly designed molecules of Schiff base-based 1, 3, 4-thiadiazole, which were then translated into 3D structures. For the molecular docking study, AutoDock Vina 1.5.6 software was employed. Lazar in silico and Swiss ADME predictors were used to calculate in silico ADMET characteristics. Results:: We have designed 111 novel Schiff base-based 1, 3, 4-thiadiazole derivatives as SGLT2 inhibitors. A total of 10 compounds from the thiadiazole series were found to have higher binding affinity to the SGLT2 protein than dapagliflozin. SSS 56 had the best docking scores and binding affinities, with -10.4 Kcal/mol, respectively. In silico ADMET parameters demonstrated that the best binding compounds were found to be non-carcinogenic with LogP = 2.53-4.02. Conclusion:: Novel Schiff base-based 1, 3, 4-thiadiazole were designed and binding affinity was assessed against SGLT2 protein, which resulted in a new lead molecule with a maximal binding affinity and estimated to be noncarcinogenic with an optimal partition coefficient (iLogP = 2.53- 4.02).

DEVELOPMENT OF NOVEL 1, 3, 4-THIADIAZOLES AS ANTITUBERCULAR AGENTS-SYNTHESIS AND IN VITRO SCREENING

Objective: Tuberculosis, known in short as TB, is considered to be a global crisis caused by Myco bacterium tuberculosis, and which continues to be a serious challenge to public health world wide especially in the developing countries. A serious problem related to tuberculosis is the development of drug resistant strains.
 Methods: Present study describes the synthesis of eight novel derivatives of 1,3,4-thiadiazole derivatives and in vitro evaluation of their anti tubercular activity against Mycobacterium tuberculosis H37 Rv strain by alamar blue assay. Pyrazinamide and Streptomycin were the standards, used for the evaluation.
 Results: Among the eight compounds synthesized one derivative was found to be active against the strain tested. All the other derivatives tested exhibited negligible activity against the strain.
 Conclusion: It can be concluded that novel 1, 3, 4-thiadiazole derivatives can be developed as novel agents in the fight against TB.

New thiadiazol azo disperse dyes derivatives and their application as a colored material for silk screen-printing ink for printing on polyester fabric

PurposeThis paper aims to synthesize new screen-printing ink formula based on new derivatives of azo thiadiazol disperse dyes and evaluate their characteristics after being printed on polyester fabric substrates.Design/methodology/approachNew dispersed dyes based on 1, 3, 4-Thiadiazole derivatives (dyes 1 and 2) were prepared and confirmed by different analyses, infrared (IR), mass and nuclear magnetic resonance (NMR) spectroscopy, and then formulated as colored materials in the screen-printing ink formulations. Printing pastes containing the prepared dyestuffs and other ingredients were used for printing polyester using screen-printing or traditional printing. The characteristics of printed polyester fabric substrates were measured by color measurements such as a*, b*, L*, C*, E, Ho, R% and color strength, as well as light, washing, crock and alkali perspiration fastness, and finally, the depth of penetration was evaluated.FindingsThe prepared 1, 3, 4-Thiadiazole derivatives (dyes 1 and 2) were obtained from the reaction of 5,5’-(1,4-phenylene)bis(1,3,4-Thiadiazole-2-amine) with resorcinol and m-toluidine as a coupling component. The suitability of the prepared dyestuffs for silk screen-printing on polyester fabrics has been investigated. The prints obtained from a formulation containing dye 1 possess high color strength as well as good overall fastness properties if compared to those obtained using dye 2.Practical implicationsThe method of synthesis of the new dyestuffs and screen-printing ink provides a simple and practical solution to prepare some new heterocyclic disperse azo dyes, and they are formulated in the screen-printing inks for printing on a polyester fabric substrate.Originality/valueThe prepared disperse dyes based on 1,3,4-Thiadiazole derivatives (dyes 1 and 2) could be used in textile printing of polyester on an industrial scale.

Molecular Docking, Synthesis, Characterization, and Preliminary Cytotoxic evaluation of new 1, 3, 4-Thiadiazole Derivatives as Αlpha-Estrogen Receptor Modulator

Objective: This study concluded that these newly synthesized analogs may be represented as an exploitable source of new anticancer agents to fight breast cancer
 Methods: Using The crystal structure of Human α Estrogen Receptor (α-ER) with a 4-HYDROXYTAMOXIFEN(standard) as a co-crystalized ligand was gained from the protein data-bank (PDB code 3ERT) as a result of docking the 1,3,4-thiadiazole derivatives compounds(M1-M3) give good docking scores compared to the standard. Compounds M1-M3 was synthesized by multistep procedures from the reaction of intermediate (benzyloxy)phenyl)-1,3,4-thiadiazole-2(3H)-thione derivatives (D1, D2) and the 4-bromo-1-(cyclic amine1-yl)butan-1-one derivatives intermediate (A1, A2). The chemical structures of the target compounds and their intermediates were confirmed by FT-IR, 1H NMR, and 13C NMR.
 Results: The in-vitro cytotoxicity assay (MTT assay) demonstrated that compounds M1-M3 showed good inhibition ratios in Breast cancer cell line (MCF-7) comparable with drug control Tamoxifen
 Conclusion: From the docking study, it was concluded that piperidine and methyl-piperazine moiety were very successful to bind tightly to alpha estrogen receptors by making numerous interaction modes.

Microwave Assisted Synthesis and Antibacterial Evaluation of 1, 3, 4-Thiadiazole Derivatives

1,3,4-Thiadiazole is an important heterocyclic moiety, forms an integral core structural component of different categories of drugs such as antimicrobial, antitubercular, anti-inflammatory, antiepileptic, antiviral, antineoplastics, and analgesic agents. It is a key moiety in current discovery and designing of new drugs. The compounds were synthesised by both conventional method and microwave method. The targeted derivatives can be synthesised in a shorter time under microwave condition than under conventional reaction condition. Their structures were confirmed by FT-IR and NMR Spectroscopy. Antibacterial property of two synthesised analogs were evaluated by Agar well diffusion method against Escherichia coli and Staphylococcus aureus. The results of antibacterial activity showed that both the compounds were active against Staphylococcus aureus and inactive against Escherichia coli. Results of invitro studies showed that modifications in SB-2-PHB and SB-8-PHB will make it as a promising lead molecule for further research.

Design, Synthesis, Molecular Docking and In silico Analysis of Some Novel 2-Amino-1, 3, 4-Thiadiazole Derivatives as Potent DNA Gyrase B Inhibitors

Introduction: Thiadiazole derivatives have been reported as a potent antimicrobial agent and the discovery of drug molecules for antimicrobial-resistant strains of Escherichia coli is still a vital challenge in the modern world. Objective: The objective of the present study is to design, synthesize and perform molecular docking studies and in-silico analysis of some novel 2-amino-1, 3, 4-thiadiazole derivatives with the aim of developing potential DNA gyrase B inhibitors. Materials and Methods: The compound 5-substituted-1, 3,4-thiadiazol-2-amine derivatives [compound 1a-1c] ; 5,6-Diphenyl- 2-[5-(substituted)-1,3,4-thiadiazol-2-yl amino]-2H -1,2,4-triazine- 3-thione derivatives [compound 2a-2c]; and propyl 3,4,5-trihydroxy-2,6-bis [5-(substituted)- 1,3,4-thiadiazol-2-yl amino] benzoate derivatives [compound 3a -3c] were synthesised by temperature- controlled microwave-assisted method. The structures of the synthesized compounds were drawn in ChemSketch. Further, molecular docking and in-silico studies for the prediction of druglikeness, pharmacokinetic parameters and prediction of toxicity were carried out . The structures of the synthesized compounds were characterized by FT-IR, 1H NMR and mass spectral analysis. Results: The synthesized compounds had a better yield.The docking studies of the synthesized compounds had a better docking score with a good binding affinity towards the protein molecule. The synthesized compounds also comply with the in-silico prediction of drug-likeness, pharmacokinetic parameters and prediction of toxicity. Conclusion: The present study reveals that the 5-substituted-1, 3,4-thiadiazol-2-amine derivatives can serve as a better lead as potent DNA gyrase B inhibitor in further drug discovery.

Synthesis and Evaluation the Activity of 1, 3, 4-Thiadiazole Derivatives as Antibacterial Agent Against Common Pathogenic Bacteria

Schiff base compound 5-(benzylideneamino)-1,3,4-thiadiazole-2-thiol was prepared from condensation reaction of 2-amino-5-mercapto-1,3,4-thiadiazole with benzaldehyde. Schiff bases react with Copper(ӀӀ), Ferric(ӀӀӀ), Cobalt(ӀӀ) and Zinc(ӀӀ) to form four complexes. The Schiff base complexes were identification by using FTIR and UV-VIS. The antibacterial activity of complexes (Copper(ӀӀ), Ferric(ӀӀӀ), Cobalt(ӀӀ) and Zinc(ӀӀ)) were studied against S. aureus and S . epidermidis as a model of Gram positive, E. coli, P. mirabilis, C. freundii and P. aeruginosa as a Gram negative model to determine activity of synthesized complexes, after subjected them to some tests to confirm the identity of the pathogenic bacteria. Ten antibiotics (Ampicillin and Amoxicillin) have been chosen to investigate the ability of bacterial isolates to resistant the conventional antibiotic. Imipenem have been selected to contrast its efficiency with those of the new compounds because of its high efficiency. The results exhibited higher activity of the new compounds proportional to the chosen antibiotics.

MOLECULAR DOCKING STUDIES ON THIADIAZOLE DERIVATIVES AS PROTEIN KINASE INHIBITORS

Objective: In the present study, a novel series of 1, 3, 4-thiadiazole derivatives were docked against the mycobacterium tuberculosis protein kinase G. 1, 3, 4–thiadiazole derivatives with a modified primary amine group at 5th position were used for docking studies.Methods: The three-dimensional structure of the protein was obtained from PDB, and its active sites were predicted. The structures of all the compounds were drawn using chemdraw software version 8.0. The docking studies were done by using schrödinger software against the enzyme protein kinase G. Totally eighteen compounds was synthesized based on glide scoreResults: In this Docking study the thiadiazole analogues were showing good binding energy. The amino acids residues GLU588, SER412, GLY410 and GLU 628 in the kinase domain active site form hydrogen bonds with the ligand.Conclusion: The compounds D34, D16, D7, D25, D15, and D27 showed better interaction with protein kinase G (pknG) more than the other drug molecules

Synthesis, theoretical, spectroscopic and electrochemical DNA binding investigations of 1, 3, 4-thiadiazole derivatives of ibuprofen and ciprofloxacin: Cancer cell line studies

Two new 1,3,4-thiadiazole derivatives of ibuprofen and ciprofloxacin namely {(5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine)} 1 and {(3-(5-amino-1,3,4-thiadiazol-2-yl)-1-cyclopropyl-6-fluoro-7-(piperazin-1-yl)quinolin-4(1H)-one)} 2 were synthesized and characterized by spectroscopic and elemental analysis. DFT and molecular docking were done initially for theoretical binding possibilities of the investigated compounds. In vitro DNA binding investigations were carried out with UV–visible spectroscopic, fluorescence spectroscopic, cyclic voltammetric (CV) experiments under physiological conditions of the stomach (4.7) and blood (7.4) pH and at normal body temperature (37 °C). Both theoretical and experimental results suggested spontaneous and significant intercalative binding of the compounds with DNA. Kinetic and thermodynamic parameters (Kb, ΔG) were evaluated greater for compound 2 which showed comparatively more binding and more spontaneity of 2 than 1 to bind with DNA at both pH values. Binding site sizes were found greater (n > 1) and revealed the possibility of other sites for interactions along with intercalation. Overall results for DNA binding were found more significant for 2 at Stomach (4.7) pH. Viscometric studies further verified intercalation as a prominent binding mode for both compounds. IC50 values obtained from human hepatocellular carcinoma (Huh-7) cell line studies revealed 2 as potent anticancer agent than 1 as value found 25.75 μM (lesser than 50 μM). Theoretical and experimental DNA binding studies showed good correlation with cancer cell (Huh-7) line activity of 1 and 2 and further suggested that these compounds could act as potential anti-cancer drug candidates.

Synthesis, Characterization of New1, 3, 4-thiadiazole Derivatives with Studying their Biological Activity

In this work, thiadiazole derivatives were prepared by taking advantage of active sites in (2-amino-5-mercapto-1,3,4-thiadiazole) as base. The main hetrocyclic compounds (1,3,4-thiadiazole, oxazole) etc. 2-amino-5-mercapto-1,3,4-thiadiazole compound [1] was prepared by cyclic closure of thiosemicarbazide compound with anhydrous sodium carbonate and carbon disulfide. Oxidation of [1] via hydrogen peroxide, to have [2] which was treat with chloro acetyl chloride to get [3]. Preparation of oxazole ring [4] obtained from reacting of [3] with urea. Schiff bases [5 – 7] prepared by reacting [3] with different benzyl aldehyde. And Preparation of derivative [8 – 11], from reaction [3] with of hydrazine derivatives. Full characterization of the synthesized compounds was done by using of spectroscopic analysis such as FT-IR, 1H-NMR and C.H.N.S,

A study on Antitumor Effect of 1, 2, 4-Thiadiazole Derivatives in Liver and Breast Cancer Cell Lines Hep G2 by Using (HCS) Technique

Multi-parametric investigation of composite poisoning at the level of specific cells, by using cellular and pour cytometry showing constructed tactics for example high-content screening, play key roles to find the poisoning and arrangement of components deepened on notice forms reversible and irreversible cellular disadvantage. To probe the effect of 1,2,4-triazole derivative cultured cellular model (liver carcinoma cell line) using HCS, this work was achieved. By an induction of apoptosis, with cells then was tested by Annexing V spotting and cell decrease as demonstrated .The products indicated that the derivative lead in the disturbance of membrane mitochondrial potential (MMP), cell tissue perviousness, nuclear abbreviation, shatter and freedom for cytochrome c of the mitochondrial addicted on cytosol. This finding suggests that derivative is a potential liver carcinoma inhibitor matched to doxorubicin as affirmative control. Also the data indicated that 1,2,4-triazole derivative possibly will have therapeutic importance in liver cancer treatment which value more development.

A Review on Antidiabetic Activity of Substituted 1, 3, 4-Thiadiazole Derivatives.

A Review on Antidiabetic Activity of Substituted 1, 3, 4-Thiadiazole Derivatives.

Synthesis and Characterization of New Heterocyclic Compounds from 2, 5- dimercapto -1, 3, 4-Thiadiazole and Their Resins

In this research, a new 1, 3, 4-Thiadiazole derivatives have been synthesized by many heterocyclic reactions. Starting from (2, 5 – dimercapto -1, 3, 4-Thiadiazole) a variety of derivatives have been synthesis. Compound (1) was synthesized by the reaction of hydrazine hydrate with carbon disulphide in absolute ethanol. The compound (1) was reacted with 1, 2-dibromoethane in presence of alkali ethanol to give the compound (2). The compound (3) was formed from the reaction of compound (2) with hydrazine hydrate. Schiff base (4) was obtained by reacting of compound (3) with the compound (p-hydroxybenzaldehyde) in absolute ethanol. A variety of phenolic Schiff base (Methylolic, Etheric, and Epoxy) derivatives have been synthesized. Methylolic derivative was synthesized by the reaction of Schiff base (4) with formaldehyde in tetrahydrofuran (THF). Etheric derivative was formed from the reaction of a methylolic Schiff base (5) with saturated alcohol (Methanol).Epoxy derivative was synthesized by the reaction of epichlorohydrine with etheric derivative (6) .The last step of this research was the preparation of a composite material from mixing the Epoxy resin derivative(7), TiO2and morpholine via ring opening. All these derivatives were verified by using (FT-IR, UV) spectra photometer and 1H-NMR spectra. Also, these derivatives were characterized using elemental analysis (C.H.N.S) .

Synthesis and Biological Evaluation of Novel 1, 3, 4-Thiadiazole Heterocyclic Derivatives as Novel Anti-Microbial Agents

Heterocyclic compounds are commonly used Scaffolds on which pharmacophores are arranged to provide potent and selective drugs. This is especially true for five-membered ring heterocyclic compounds, which serve as the core components of many substances that possess a wide range of interesting biological activities. New series of 1, 3, 4-Thiadiazole derivatives were synthesized From Benzyl Isocynate and Acid hydrazide, by using P-TsCl in NMP, The Novel Derivatives have been screened for their antimicrobial activity.

Synthesis and Characterization of New Heterocyclic Compounds from 2, 5- dimercapto -1, 3, 4-Thiadiazole and Their Resins

In this research, a new 1, 3, 4-Thiadiazole derivatives have been synthesized by many heterocyclic reactions. Starting from (2, 5 – dimercapto -1, 3, 4-Thiadiazole) a variety of derivatives have been synthesis. Compound (1) was synthesized by the reaction of hydrazine hydrate with carbon disulphide in absolute ethanol. The compound (1) was reacted with 1, 2-dibromoethane in presence of alkali ethanol to give the compound (2). The compound (3) was formed from the reaction of compound (2) with hydrazine hydrate. Schiff base (4) was obtained by reacting of compound (3) with the compound (p-hydroxybenzaldehyde) in absolute ethanol. A variety of phenolic Schiff base (Methylolic, Etheric, and Epoxy) derivatives have been synthesized. Methylolic derivative was synthesized by the reaction of Schiff base (4) with formaldehyde in tetrahydrofuran (THF). Etheric derivative was formed from the reaction of a methylolic Schiff base (5) with saturated alcohol (Methanol).Epoxy derivative was synthesized by the reaction of epichlorohydrine with etheric derivative (6) .The last step of this research was the preparation of a composite material from mixing the Epoxy resin derivative(7), TiO2and morpholine via ring opening. All these derivatives were verified by using (FT-IR, UV) spectra photometer and 1H-NMR spectra. Also, these derivatives were characterized using elemental analysis (C.H.N.S) .

Tautomerism of 2-Azido-1, 3, 4-Thiadiazole Studied by Theoretical Methods in Gas Phase and Solution

The tautomeric equilibrium of 2-azido-1, 3,4-thiadiazole and [1,3,4] thiadiazolo [3,2-e] tetrazole derivatives (5-H, 5-F, 5-Cl, 5-CH3, 5-CH2CH3, 5-NO2, 5-CN) has been investigated using HF, B3LYP and MP2 level of calculation with the 6-311G (d, p) in the gas phase and solution with full geometry optimization. The calculation results demonstrate 2-azido-1, 3, 4-thiadiazole derivatives are more stable. In addition variation of dipole moments, charges on atoms, HOMO, LUMO and the interfrontier molecular orbital energy gap are studied.

Review article on 2, 5-Disubstituted-1, 3, 4-Thiadiazole Derivatives and its Pharmacological Activities

Heterocyclic compounds are the nucleus of the compound that provides life to the compound. It occupies the central position. In recent years it has been found that 1,3,4-thiadiazole and derivatives had gained many importance because of having extensive pharmacological activities, possibly due to the presence of toxophoric N2C2S moiety. It possess unique anti-inflammatory, analgesic, antimicrobial, anticonvulsant, antidiabetic, antitumor, antiviral activities. In the pursuit and design of new drugs, the development of hybrid molecules through the combination of different molecules in one frame may lead to compounds with interesting biological profiles. This review presents the recently synthesized 1,3,4-thiadiazole derivatives having important biological activities.

Comparative studies on Synthesis of 2-Chloro-N-(2, 5-Dihydro-1, 3, 4-Thiadiazol-2-Yl) Acetamide using Microwave irradiation and Conventional techniques and their Antioxidant activity

The advantages of Microwave irradiation technology in the field of organic chemistry have been long known as it facilitates accelerated reaction rates, higher yields with relatively less power consumption than classical techniques. The presented study compares aspects like reaction time and percentage yield of various 2- amino-1, 3, 4-thiadiazole derivatives when synthesized by both, conventional as well by microwave irradiation along with their characterization using techniques such as FTIR and HPLC. They have a very promising role in the field of medicinal chemistry owing to their anti-cancer and anti-fungal properties The study also aims to evaluate biological activity of the compounds a simple and inexpensive technique making use of 2,2-Diphenyl-1- picrylhydrazyl(DPPH) to establish their worth as potential anti-oxidants . Thus this combination of faster synthesis and cost effectiveness can significantly reduce the cost of production of various pharmaceutical products containing thiadiazole and/or its derivatives which are known to be clinically potent.

Design and synthesis of conformationally restricted capsaicin analogues based in the 1, 3, 4-thiadiazole heterocycle reveal a novel family of transient receptor potential vanilloid 1 (TRPV1) antagonists

4-hydroxy-3-methoxybenzaldehyde was used as starting material to obtain a number of 1, 3, 4-thiadiazole alkylamide derivatives. The pharmacological properties of these conformationally restricted capsaicin analogues were evaluated on HEK-293T cells transiently expressing TRPV1 receptor. By means of a highthroughput calcium imaging assay we find that 1, 3, 4-thiadiazoles (compounds 8–15) act as potent antagonists of the capsaicin receptor, inhibiting both, the capsaicin- and temperature-dependent activation. Docking studies suggested a different binding orientation on the vanilloid binding site when compared with capsaicin analogues, such as 5-iodononivamide. Overall, our studies suggest that 1, 3, 4-thiadiazoles interact with capsaicin's binding region of the receptor, although using a different set of interactions within the vanilloid binding pocket.