Thiosemicarbazide Derivatives Research Articles

Synthesis, characterization, computational study, and screening of novel 1-phenyl-4-(2-phenylacetyl)-thiosemicarbazide derivatives for their antioxidant and antimicrobial activities

Condensation reaction of phenyl acetyl isothiocyanate (1) and phenyl hydrazine was performed to obtain 1-phenyl-4-(2-phenylacetyl) thiosemicarbazide (2). Compound (2) was utilized as starting material for synthesis of different fused 1,2,4-triazole compounds. Reaction of (2) with hydrazine hydrate, anthranilic acid and ethyl glycinate under microwave irradiation and traditional thermal conditions afforded 1,2,4-traizol derivatives (4, 5 and 6) respectively. On the other hand, cyclization reaction of compound (2) under microwave irradiation gave 1,2,4-triazole-3-thione derivative (3). The microwave assessed reaction produced higher yield reaction and purity than the traditional thermal reaction. The chemical structures of the synthesized compounds were elucidated using elemental analysis, FTIR, 1H NMR, and GC/MS spectroscopy. The synthesized compounds (2–7) were evaluated for their antimicrobial and antioxidant potentials. Density functional theory (DFT) was evaluated at B3LYP/3-21G level to study the electronic and geometric characteristics of (4–6) compounds including the optimized structures, relative binding energies, atomic charges, position of HOMO and LUMO of the molecules.

Synthesis, Molecular Docking Studies and In Silico ADMET Screening of New Heterocycles Linked Thiazole Conjugates as Potent Anti-Hepatic Cancer Agents.

Thiazoles are important scaffolds in organic chemistry. Biosynthesis of thiazoles is considered to be an excellent target for the design of novel classes of therapeutic agents. In this study, a new series of 2-ethylidenehydrazono-5-arylazothiazoles 5a–d and 2-ethylidenehydrazono-5-arylazo- thiazolones 8a–d were synthesized via the cyclocondensation reaction of the appropriate hydrazonyl halides 4a–d and 7a–d with ethylidene thiosemicarbazide 3, respectively. Furthermore, the thiosemicarbazide derivative 3 was reacted with different bromoacetyl compounds 10–12 to afford the respective thiazole derivatives 13–15. Chemical composition of the novel derivatives was established on bases of their spectral data (FTIR, 1H-NMR, 13C-NMR and mass spectrometry) and microanalytical data. The newly synthesized derivatives were screened for their in vitro anti-hepatic cancer potency using an MTT assay. Moreover, an in silico technique was used to assess the interaction modes of the compounds with the active site of Rho6 protein. The docking studies of the target Rho6 with the newly synthesized fourteen compounds showed good docking scores with acceptable binding interactions. The presented results revealed that the newly synthesized compounds exhibited promising inhibition activity against hepatic cancer cell lines (HepG2).

Thiosemicarbazide-modified/ion-imprinted phenolic resin for selective uptake of cadmium ions

Cd(II)-imprinted Cd(II) resin obtained from a thiosemicarbazide derivative of salicylic acid was prepared and evaluated for selective uptake of Cd(II) ions. In the beginning, the thiosemicarbazide derivative of salicylic acid (H2TCS) was developed as a functional ligand that was then coordinated with Cd(II) ions to obtain the Cd-complex [CdTCS(H2O)3]. After the full investigation of the ligand and its complex, they copolymerized with resorcinol in presence of formalin, and the obtained resinous material was eluted with 0.1 M HNO3 solution to extract the polymer incorporated Cd(II) ions and finally produce the Cd(II) ions selective Cd-RTCS sorbent. The maximum cadmium ions capacity by the Cd-RTCS reached 164 ± 1 mg/g, which could be a relatively high and promising value. Also, the adsorption isotherms were interpreted better with the Langmuir model. In addition, the Cd(II) sorption using Cd-RTCS was tested in a competitive medium of Pb(II), Ni(II), Zn(II), and, Cu(II) ions and the results indicated a considerable selectivity toward the Cd(II) ions over the coexisted metals.

Synthesis and antioxidant evaluation of some heterocyclic candidates from 3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-(4-oxo-4H-benzo[d][1,3]oxazin-2-yl)propenonitrile

A new series of quinazoline derivatives bearing a 1,3-diphenylpyrazole core was synthesized starting from 3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-(4-oxo-4H-benzo[d][1,3]oxazin-2yl)propenonitrile (4) through reactions with some nitrogen nucleophiles. Hydrazinolysis of 4 furnished the biquinazoline and diheterylazine derivatives depending on the reaction conditions. Noteworthy, the benzimidazole derivatives were obtained via treatment with 2-aminoaniline under different reaction conditions. Inspect of the reactions of 4 with hydrazinecarbothioamide and hydrazinecarbothiohydrazide provided thiosemicarbazide, triazepinoquinazoline, and mercaptotetrazine derivatives. The antioxidant screening disclosed that some of these compounds such as 3, 5, 11, 12, and 13 exhibited significant potency.

Acryloyl isothiocyanate skeleton as a precursor for synthesis of some novel pyrimidine, triazole, triazepine, thiadiazolopyrimidine and acylthiourea derivatives as antioxidant agents

ABSTRACT The reactions of 2-cyano-3-pyrazolylpropenoyl isothiocyanate derivative 2 with some mono- and bidentate nucleophiles namely, dodecan-1-amine, 6-aminothiouracil, hydrazine, phenylhydrazine, phenylurea, semicarbazide, and thiosemicarbazide, in addition to some derivatives of hydrazides, have been investigated to obtain some valuable heterocyclic skeletons gathering with a pyrazole core, viz. pyrimidine, triazole, triazepine, thiadiazolopyrimidine as well as acylthiourea derivatives. Hydrazinolysis of 2 was found to provide a mixture of thiosemicarbazide, diheterylazine, and triazepine derivatives. Treatment of 2 with phenylhydrazine was mainly dependent on the reaction conditions to produce a mixture of pyrimidinethione and triazole derivatives at room temperature or the triazepine derivative at heating conditions. The antioxidant activity screening of these compounds disclosed that pyrimidinethione derivatives 9 and 13 exhibited the most potency.

Synthesis, Characterization and antioxidant activities of Semicarbazide and Thiosemicarbazide Derivatives

In this research work Semicarbazide, thiosemicarbazide derivatives 3 to 25 were synthesized by conventional methods with high percentage yield and reaction rate. 1H-NMR and EIMS spectroscopic techniques were used to elucidate the structure of the synthesized compounds. The effect of thiosemicarbazide and semicarbazide derivatives as an antioxidant agents were studied by DPPH free radical scavenging, ferric ion reducing, ferrous ion chelating assays. Higher DDPH radical scavenging activity exhibited by most of the compounds as compared to standard vitamin C. Excellent ferric ion reducing activity was indicated by compounds of theseriesas compared to standard vitamin C. However most of the compounds generally showed average ferrous ion chelating activity than standard EDTA.

Synthesis, Characterization and antioxidant activities of Semicarbazide and Thiosemicarbazide Derivatives

In this research work Semicarbazide, thiosemicarbazide derivatives 3 to 25 were synthesized by conventional methods with high percentage yield and reaction rate. 1H-NMR and EIMS spectroscopic techniques were used to elucidate the structure of the synthesized compounds. The effect of thiosemicarbazide and semicarbazide derivatives as an antioxidant agents were studied by DPPH free radical scavenging, ferric ion reducing, ferrous ion chelating assays. Higher DDPH radical scavenging activity exhibited by most of the compounds as compared to standard vitamin C. Excellent ferric ion reducing activity was indicated by compounds of theseriesas compared to standard vitamin C. However most of the compounds generally showed average ferrous ion chelating activity than standard EDTA.

An Updated Review on Synthesis and Biological Activities of Thiosemicarbazide Analogs

This review paper focuses on the different synthetic methodologies that researchers have adopted to synthesize various thiosemicarbazide derivatives with different biological activities of synthesized compounds in the last 20 years. Most of the investigations available in the literature are directed to the biological activities of thiosemicarbazide derivatives with less discussion on its synthetic schemes. This review article presents various reaction scheme, which has been adopted for thiosemicarbazide derivative synthesis along with the reported pharmacological activities of synthesized analogs. The available literature in the article aims to encourage more studies on the synthesis of thiosemicarbazide derivatives, which will help for drug discovery having thiosemicarbazide nucleus.

Anticorrosion effect of thiosemicarbazide derivative on mild steel in 1 M hydrochloric acid and 0.5 M sulfuric Acid: Gravimetrical and theoretical studies

The worldwide economic challenge of metal corrosion is crucial. The use of inhibitors, particularly organic inhibitors, is one of the greatest strategies to protect metal surfaces against corrosion. This research evaluates anti-corrosive characteristics of inhibitor compound (EOPT) namely 4-ethyl-1-(4-oxo-4-phenylbutanoyl)thiosemicarbazide on mild steel (MS) in 1 M HCl and 0.5 M H2SO4 solutions. The inhibition efficiency of EOPT was investigated utilizing weight loss measurements (WL), adsorption isotherm, and theoretical investigation utilizing density functional theory (DFT) within the concentration range of 100 to 600 ppm at the solution Temperature 303, 313, 323 and 333 K for the exposure period 1, 5, 10, and 24 h. The experimental findings showed that increasing the concentration of EOPT increases the inhibition efficiency (from 67.4 to 96.1% in HCl solution and from 55.3 to 88.7% inH2SO4 solution for 500 ppm and immersion time 5 h), whereas the inhibitive efficacy order for EOPT is HCl solution > H2SO4 solution with the significant inhibiting efficacy, each of 97.0, and 89.9% for 600 ppm and immersion time 10 h. Additionally, WL analyses showed that the adsorption of EOPT molecules obeys the Langmuir isotherm model in both acidic solutions. The studied inhibitor is well absorbed by the sites of adhesion on the MS surface by all the chemical descriptors determined from the DFT. The molecular geometry and electronic structure were determined by applying quantum chemical computations. DFT calculated to depict chemical reactivates and kinetic stabilities of the molecular structure, the energies between frontier molecular orbitals have been calculated (HOMO and LUMO).

Synthesis Characterization and In Vitro Antibacterial Activity of the N-Substituted Bis-Pyrazoline Derivative as Polycyclic Aromatic Compounds

N-substituted bis-pyrazolines were synthesized by the reaction of bis-chalcone with N-substituted thiosemicarbazide derivatives under basic conditions. Bis-chalcone was synthesized by the reaction of 1-(2,5-dimethylthiophen-3-yl)ethan-1-one with terephthalaldehyde under basic condition. The structure of the bis-pyrazoline derivatives has been confirmed by spectroscopic techniques such as FT-IR, 1H-NMR, 13C-NMR, and ESI-MS spectra, and the purity of the compound has been confirmed by the elemental analysis. The in vitro antibacterial activity of these pyrazoline derivatives was estimated against two Gram-positive and two Gram-negative bacterial strains by the disk diffusion method and minimum inhibitory concentration (MIC) method and the results were compared with standard drug Amoxicillin. The structure-activity relationship shows that the compound with choloro aromatic substituents at thiacarbomoyl group was more active than standard drug Amoxicillin.

Electrochemical synthesis for new thiosemicarbazide complexes, spectroscopy, cyclic voltammetry, structural properties, and in silico study

A new thiosemicarbazide derivative ligand (HDCTS) was prepared from the reaction between 2,4‐dinitrophenylhydrazine and 4‐chlorophenyl isothiocyanate. Co(II) and Cu(II) complexes were synthesized from HDCTS derivative by electrochemical method to reach preferable yield in a safe environment. The new complexes as well as the original ligand were fully characterized to establish their chemical formulae. The spectral (infrared, Raman, mass, and ultraviolet–visible), analytical (elemental, thermogravimetric analysis [TGA], and cyclic voltammetry), and conformational techniques were implemented for characterization. According to spectral data and magnetic moments, the octahedral arrangement was proposed around metals through mono‐negative bidentate mode of bonding. TGA discriminates and quantitatively evaluates the presence of water molecules within two complexes. Electrochemical study was interested for all new compounds and suggests the electrode couples to be close for quasi‐reversible behavior. Elaborated conformational study was displayed to extract significant characteristics, which assert firstly on the mode of bonding inside the complexes. The perfect distribution of NH and CS groups inside the optimized structures facilitates their coordination as spectrally proposed. Crystal explorer program was used to investigate the degree of contact between molecules inside crystal packing systems. Effective contribution in surface contact feature was noticed from O and Cl atoms. A certified in silico study concerning the docking feature of new compounds against effective proteins in allergy and inflammation diseases was done. According to data exported, a promising anti‐allergic or anti‐inflammatory efficiency is expected strongly from Cu(II)–DCTS complex.

Synthesis and Study of Some fused Substituted 1,3,4-Thiadiazoles and 1,2,4-Triazoles from 4-Chloro- phenoxy acetic acid and 2,4-dichlorophenoxy acetic acid

In this work the synthesis of some substituted 1,2,4-triazoles and five ring system's reported. 2-(4-Chlorophenoxy) acetic acid (S1) was synthesis from corresponding substituted phenol by its reaction with chloroacetic acid in sodium hydroxide solution, the acids (Q1 and S1) esterified with methanol and sulfuric acid to give esters (Q2 and S2) which converted to acid hydrazides (Q3 and S3) by their reaction with hydrazine hydrate in ethanol. The acid hydrazides (Q3 and S3) were treated with carbon disulfide in potassium hydroxide solution to give potassium salts (Q4 and S4) the formed salts were treated with hydrazine hydrate to give substituted 4-amino-1,2,4-triazoles (Q5 and S5). 4-Amino-1,2,4-Triazole (Q5 and S5) were converted to (Q6 and S6), (Q9 and S9) and (Q10 and S10) by treating with CS2 in pyridine, urea and chloroacetic acid. While reaction of 4-amino-1,2,4-triazole (Q5 and S5) with phenyl isothiocyanate gave thiosemicarbazide derivatives (Q7 and S7) that converted to N-phenyl substituted 1,2,4-triazole (Q8 and S8). The structures of the synthesized compounds were confirmed by physical and spectral data.

Isatin based thiosemicarbazide derivatives as potential inhibitor of α-glucosidase, synthesis and their molecular docking study

A new series of isatin based thiosemicarbazide derivatives 1–15 were synthesized and characterized by 1H NMR, 13C NMR and HR-EIMS. The synthetic derivatives were evaluated for α-glucosidase inhibitory potential. All compounds showed excellent α-glucosidase inhibitory potential having IC50 values ranging between 1.20 ± 0.10 to 35.60 ± 0.80 µM when compared with the standard acarbose having IC50 value 38.60 ± 0.20 µM. Compound 3, 4, 5, 9, 10, 12 and 15 having IC50 values 2.20 ± 0.10, 3.5 ± 0.10, 1.20 ± 0.10, 5.20 ± 0.20, 3.60 ± 0.10, 4.60 ± 0.20 and 3.90 ± 0.10 µM, respectively, was found many fold better than the standard acarbose having IC50 value 38.60 ± 0.20 µM. Structure activity relationship has been also established for all newly synthesized compounds, mainly based on substitution pattern on phenyl ring. Through molecular docking study the binding mode of active derivatives with α-glucosidase enzyme active site was confirmed.

Comparative biological study between quinazolinyl-triazinyl semicarbazide and thiosemicarbazide hybrid derivatives.

Practical synthesis and biological activities of quinazolinyl-triazinyl semicarbazides (10a-j) and quinazolinyl-triazinyl thiosemicarbazides (11a-j) have been described. The novel semicarbazides and thiosemicarbazides were prepared by condensation of different nucleophiles like isocyanate and isothiocyanate by the displacement of chlorine atoms on the basis of functionality concept on varying conditions. The synthesized quinazolinyl-triazinyl semicarbazide and thiosemicarbazide derivatives were evaluated for their expected antimicrobial activity. All the final synthesized derivatives were characterized by their melting point, mass spectra, 1H NMR and 13C NMR as well as elemental microanalysis. The final analogues were then analyzed for their in vitro antimicrobial activity against bacteria (Gram positive and negative) and fungus using the agar streak dilution method as well as in vitro anti-HIV activity against two types of viral strains, viz. HIV type I (IIIB) and type II (ROD) by using MTT assay method. SAR and HOMO-LUMO studies were also carried out for proving the structural biological activity. Among them, compounds 10e, 10f, 11h and 11j gave best results as their energy gap is very low which makes their activity higher.

Microwave assisted synthesis and antimicrobial evaluation of novel substituted thiosemicarbazide derivatives of pyrimidine

AbstractA new series of antimicrobial thiosemicarbazide substituted pyrimidine derivatives were synthesized by using thiosemicarbazide and ethyl 2‐((2‐amino‐5‐carbamoyl‐6‐[substituted benzyl] pyrimidin‐4‐yl)oxy)acetate derivatives and subsequent addition of acetaldehyde and acetone. The designed compounds were screened for Antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumonia in comparison with the standard drugs Ciprofloxacin and antifungal effect against Aspergillus niger and Aspergillus fumigates in comparison with the standard drug Ketoconazole reveal the potency of synthesized derivatives. In accordance with the data obtained from antimicrobial activity, all the synthesized derivatives have shown good activity against the tested microbes. Among them, compound bearing 2‐hydroxy and 3‐chloro derivatives of thiosemicarbazide substituted pyrimidine has shown good activity against all the tested organisms.

Cyclization of thiosemicarbazide derivative: As a source of novel synthesis of some azoles and azines

AbstractIn our study, we aimed to synthesize novel, some biologically active compounds, Azoles and Azines derivatives, that to be nitrogen‐containing heterocycles, and have their diverse therapeutic values. Thiosemicarbazide, 2, was obtained from the attack of nitrogen of hydrazine to the carbon of heteroallene function of compound 1. Triazolotriazole derivative, 4, was obtained from the reaction of 2 with diethyl malonate. Cyclization of thiourea unit of compound 2 with heteroallene, 1, gave trazine, 6. Benzolyation of 2 using benzoyl chloride formed triazole derivative, 8. Reaction of 2 and maleic anhydride gave furothiadazine, 10. Cyclohexanopyrimidinthione, 12, was obtained from cyclocondensation of cyclohexanone with 2. Triazole, 14, was obtained from 2 and ammonium isothiocynate under thermal condition. Reaction of 2 with ethyl bromoacetate gave thiazole derivative, 16. [2+3] Cyclocondensation of acetyl acetone with 2 provided pyrazole, 18. Triazolotriazole, 20, was obtained from formalin and 2. Compound 2 suffers intramolecular base mediated cyclization affording pyrazole, 21. Keeping 2 and propinaldehyde under reflux provided triazolotriazole, 24. Acylation of 2 by succinic acid formed pyridazine derivative, 27.

Elaborated computational studies for Zn(II) and Sn(II) complexes, electro-synthesis, spectral, thermal and electrochemical analysis

New Zn(II) and Sn(II) complexes were electrochemically synthesized from thiosemicarbazide derivative. New isolated complexes were analytically characterized to be 1: 2 M ratio (M:L). The spectral techniques demonstrate the coordination attitude as a mono-negative bi-dentate mode within tetrahedral geometry. Intra-ligand and charge transfer transitions were assigned in complexes and appeared different from that in original ligand. Electrochemical cyclic voltammograms were obtained to establish a view about oxidation/reduction electrode couples, which mostly appeared quasi-reversible. Crystal packing features were recognized through calculating Hirshfeld surface properties by using advanced programs. Based on data and statistics obtained, a significant contact surface appeared between molecules of Zn(II) complex inside cubic crystal. Also, XRD patterns were drawn on Crystal Maker program, to know the feature of unit cell which appeared as a simple cube. Conformational study was executed under double-zeta polarized basis set, to display best structural forms and calculating significant physical parameters (as Fukui indices). Also, UV–Vis spectra were obtained after executing the geometry optimization process to elucidate some essentials. Finally, it is worthy to note that, the docking simulation here was applied through opposing routes, one to evaluate the anti- pneumonia feature and the other to know the side effects on important protein as collagen. A promising attitude was appeared by Sn(II) complex in the two routes.

DFT Theoretical Study of Some Thiosemicarbazide Derivatives with Copper

Проведені теоретичні дослідження виявлення слідів міді у водному розчині з використанням двох похідних тіосемікарбазидів як лігандів: 4-етил-3-тіосемікарбазиду і тіосемікарбазиду. Експериментальні дослідження проведені за допомогою адсорбційної інверсійної вольтамперометрії. Квантово-хімічні розрахунки виконані на базі 6-31G(d) у поєднанні з методом апроксимації локальної спінової щільності та реалізовані в пакеті програм Gaussian 09. Доведено наявність значної залежності між сумарною енергією комплексів міді та межею виявлення: чим стабільніший комплекс, тим нижча межа виявлення. Отримані результати добре узгоджуються з експериментальними висновками.

HYDRAZIDE OF o-HYDROXYBENZOIC ACID AND ITS DERIVATIVES. SYNTHESIS AND PROPERTIES

The article presents the results of a study by the authors of the article on the development of new ways of synthesis and study of the biological activity of hydrazide derivatives of o-hydroxybenzoic acid. Methods for the preparation of hydrazone, oxadiazole, thiosemicarbazide, 1,2,4-triazole-3-thionic derivatives and methods for their further modification are described. The condensation reaction of hydroxybenzoic acid hydrazides with 1-deoxy-2,3,4,6-tetra-O-acetyl-D-glucopyranosyl isothiocyanate synthesized their corresponding acetylated glycosyl-contai-ning thiosemicarbazide derivatives. The structures of the synthesized compounds were studied by 1H and 13C NMR spectroscopy, as well as by the data of two-dimensional spectra of COSY (1H-1H) and HMQC (1H-13C). The values of chemical shifts, multiplicity, and integrated intensity of 1H and 13C signals in one-dimensional NMR spectra were determined. Using spectra in the formats COSY (1Н-1Н) and HMQC (1Н-13С), homo- and heteronuclear interactions were established, confirming the structure of the compounds under study. The results of evaluating their antimicrobial, anti-inflammatory and cytotoxic activity (in vitro) on cultures of human monocytic cell lines MonoMac-6 and THP-1Blue are described.

2,4-Dichlorophenoxyacetic Thiosemicarbazides as a New Class of Compounds Against Stomach Cancer Potentially Intercalating with DNA.

Thiosemicarbazide is a useful structural moiety that has the biological potential. Optimization of this structure can result in groundbreaking discovery of a new class of therapeutic agents. In the light of this, 1-(2,4-dichlorophenoxy)acetyl-4-(1-naphthyl)thiosemicarbazide (1) and 1,4-bis[(2,4-dichlorophenoxy)acetylthiosemicarbazide]phenyl (2) were synthesized and characterized by spectroscopic method. Cytotoxicity of obtained compounds was evaluated on MKN74 gastric cancer cell line and human skin fibroblast BJ based on methylthiazolyldiphenyl-tetrazolium bromide (MTT) test. The apoptosis/necrosis and cell cycle analysis were conducted using image cytometry. Additionally, in DNA of treated cells, abasic sites (AP) and double strands breaks (DSB) presence were measured. Intercalating properties of active compounds were evaluated using the UV–spectroscopic method. Among newly synthesized derivatives, compound 2 showed toxic effects on gastric cancer cells with simultaneous lack of toxicity to normal fibroblasts. Cell cycle analysis revealed that both compounds influence cell division mainly at the stage of replication. Simultaneously with DNA synthesis disorders, DNA damages like AP-sites and DSBs were observed. Spectroscopic studies revealed possible DNA intercalating properties of tested compounds. Obtained results indicate that the newly synthesized thiosemicarbazide derivatives are a promising group of compounds with potential anticancer activity resulted from interactions with DNA and cell cycle interrupt.