Reaction Of Thiosemicarbazones Research Articles

Synthesis and Characterization of some new heterocyclic derivatives from aromatic carbonyl ‎compounds and carboxylic acids with Evaluation some of them for biological activity

In this research investigation, a total of eighteen diverse tetra- and penta-lateral cyclic compounds were synthesized. These included 1,3,4-thiadiazole, thiazolidin-4-one (via an alternative method), 1,2,4-triazole, carbothioamide, thiazole-4-one, azetidin-2-one, and oxazole. The synthesis procedure entailed a sequence of reactions. The thiazolidine-4-one 1 was obtained by reaction p-aminobenzoic acid with thiosemicarbazide, followed by treatment with p-tolualdehyde to produce Schiff base 2. Reaction Schiff base 2 with mercaptoacetic acid in dry benzene was carried out to produce thiazolidine-4-one 3. In another synthesis pathway, the esterification of p-nitro benzoic acid with ethanol in the presence of sulfuric acid was obtained to formation of compound 4. Compound 4 was subsequently reacted with thiosemicarbazide, yielding compound 5. Cyclization of compound 5 was then achieved using 4% sodium hydroxide solution. This formed the 1,2,4-triazole heterocycle, designated compound 6. Thiosemicarbazone 7-9 were prepared by reaction of thiosemicarbazide with different aldehydes. Additionally, 2-substituted-1,3-thiazolidine-4-one derivatives 10-12 were synthesized through the reaction of thiosemicarbazone with chloroacetic acid in the presence of anhydrous sodium acetate. The Oxazole derivative 15 was obtained through a series of reactions starting with the reaction of p-amino benzoic acid with ethyl chloroacetate, resulting in compound 13. Compound 13 was then treated with urea to obtain compound 14, followed by a reaction with 4-phenyl phenacyl bromide to yield the final product, the Oxazole derivative 15. The 2-aminooxadiazole derivative 16 was synthesized by reaction urea with 4-bromoacetophenone which was reacted with 4-bromobenzaldehyde to produce Schiff base derivative 17. Finally, β-lactam 18 is obtained through reaction Schiff base with chloroacetyl chloride in the presence of triethyl amine. FT-IR, 1H-NMR, and 13C-NMR spectroscopy were used to confirm their proposed structures. Moreover, the antibacterial and antifungal activities of certain synthesized compounds, specifically 2,3,6,11,13,15,17, and 18, were assessed against Staphylococcus aureus, Escherichia coli, and Candida albicans, demonstrating encouraging outcomes.Keywords: Antibacterial, antifungal activity, oxadaizole, heterocyclic derivatives, Oxazole.

Development of novel indolin-2-one derivative incorporating thiazole moiety as DHFR and quorum sensing inhibitors: Synthesis, antimicrobial, and antibiofilm activities with molecular modelling study

Nowadays, it's imperative to develop novel antimicrobial agents active against both drug-sensitive and drug-resistant bacterial infections with favorable profiles as high efficacy, low toxicity, and short therapy duration. Accordingly, a series of new thiazolo-indolin-2-one derivatives were synthesized based on acid and base catalyzed condensation or reaction of thiosemicarbazone 8 with different electrophilic reagents. The structure of the new compounds was confirmed based on elemental analysis and spectral data. Based on the MIC results, the most active thiazolo-indoline derivatives 2, 4, 7a, and 12 exhibited promising antibacterial activity against gram-positive and gram-negative bacteria with weak to moderate antifungal activities. Surprisingly, the N-(thiazol-2-yl)benzenesulfonamide derivative 4 was found to be most active on antibiofilm activity against both S. aureus (ATCC 29213) with BIC50 (1.95 ± 0.01 µg/mL), while 5-(2-oxoindolin-3-ylidene)-thiazol-4(5H)-one derivative 7a exhibited the strongest antibiofilm activity against P. aeruginosa pathogens with BIC50 (3.9 ± 0.16 µg/mL). Further, the thiazole derivatives 2, 4 and 12 exhibited a significant inhibition activity against the fsr system in a dose-dependent manner without affecting bacterial growth. The target derivatives behaved synergistic and additively effect against MDR p. aeruginosa, and thiazole derivative 12 exhibited a high synergistic effect with most tested antibiotics except Cefepime with FIC value ranging between 0.249 and 1.0, reducing their MICs. Interestingly, the 3-(2-(4-thiazol-2-yl)hydrazono)indolin-2-one derivative 12 displayed the highest selectivity to DHFR inhibitory with IC50 value 40.71 ± 1.86 nM superior to those of the reference Methotrexate. Finally, in silico molecular modeling simulation, some physicochemical properties and toxicity predictions were performed for the most active derivatives.

Microwave‐assisted synthesis and antimicrobial activity of novel spiro 1,3,4‐thiadiazolines from isatin derivatives

This work describes the synthesis of spiro 1,3,4‐thiadiazolines from isatin‐β‐thiosemicarbazone acetylation, using microwave irradiation as a source of heating the reaction medium. N‐substituted isatin derivatives were used as substrates to obtain thiosemicarbazones by adding thiosemicarbazide to the isatin ketone carbonyl. The final synthetic step was the reaction of thiosemicarbazones with acetic anhydride under microwave irradiation to get the spiro compounds. Reaction times ranged from 6 to 18 minutes resulting in yields of up to 90%. Biological assays have shown promising antibacterial and antifungal activity, especially spiro thiadiazolines derived from allylated isatins. All the proposed molecules proved to be potential drug candidates based on the results of the in silico investigation, with satisfactory drug‐likeness and drug‐score, respecting Lipinski's rule. The use of the microwave reactor was efficient for the synthesis of thiosemicarbazones and spiro compounds, resulting in a significant reduction in reaction times with conventional heating. Taking into account the threat of antimicrobial resistance, this work presents a series of bioactive molecules that are easily obtained via microwave reaction.

Synthesis, identification and antimicrobial activity of substituted thiazolines and 1,3,4-thiadiazines from dehydroacetic acid

The reaction of thiosemicarbazones with various α-chloroketones in the presence of anhydrous NaOAc led to 4-thiazolines 5, 7 or 1,3,4-thiadiazines 11 in good yields. Structure elucidation was carried out by 1H, 13C, and FT-IR spectroscopy. The purity of these new products was confirmed by HRMS. A possible mechanism for the formation of 5, 7, and 11 was discussed. All the synthesized novel 4-thiazoline and 1,3,4-thiadiazine derivatives were evaluated in vitro for their antibacterial and antifungal activities against six pathogenic bacteria and a strain of yeast: Escherichia coli ATCC 25992, Pseudomonas aeruginosa ATCC 27852, Staphylococcus aureus ATCC 25923 methicillin-resistant, Staphylococcus aureus ATCC 43300 methicillin-sensitive, Micrococcus luteus ATCC 4698 Enterococcus faecalis ATCC 29212 and Candida albicans IPA (200). Some compounds exhibited relatively significant antibacterial and antifungal activities.

Terephthalaldehyde: An Effecient Key Precursor for Novel Synthesis of Some Interesting Bis‐thiazoles and Bis‐triazolopyrimidinones

Novel bis‐thiazoles were synthesized in high and efficient yields from the reaction of thiosemicarbazones with halogenated compounds. Also, new bis‐triazolopyrimidines were prepared from the reaction of hydrazonoyl chlorides with bis‐thione derivative. All prepared compounds were fully characterized by spectral methods. The synthesized bis‐compounds will be attractive species for the medicinal researchers to investigate their biological activity.

Azines from one-pot reaction of thiosemicarbazones

ABSTRACTThermolysis and/or microwave irradiation of thiosemicarbazones gave the corresponding isothiocyanates, which on addition of either activated nitriles or aldehydes furnished various types of azines. The mechanism was discussed. The structures of products were proved by MS, IR, NMR, and elemental analyses.

In situ generation of functionalized 1,2,4-triazole-5-thiones containing pyridine or pyrazine moieties and their coordination to HgII

The reaction of 2-cyanopyridine or 2-cyanopyrazine with N-methylthiosemicarbazide afforded (Z)-2-(amino(pyridin-2-yl)methylene)-N-methylhydrazinecarbothioamide (HPyAm4M) and (Z)-2-(amino(pyrazin-2-yl)methylene)-N-methylhydrazinecarbothioamide (HPzAm4M), respectively. Prolonged heating under reflux in methanol in the synthesis of these thiosemicarbazones led to the formation of 4-methyl-5-pyridin-2-yl-2,4-dihydro-[1,2,4]triazole-5-thione (HMPytat, 1) and 4-methyl-5-pyrazin-2-yl-2,4-dihydro-[1,2,4]triazole-5-thione (HMPztat, 2) by oxidative cyclization of the starting thiosemicarbazones. Reactions of thiosemicarbazones with mercury(II) salts gave new complexes of general formulae [Hg(tat)X] (3, 4) and [Hg(Htat)2X2] (5, 7, 9–11), along with [Hg3(HEPytat)2(EPytat)2Cl4]·3H2O (6) and [Hg(EPytat)(HEPytat)I]·H2O (8) (Htat = general 1,2,4,-triazole-5-thione). The complexes were isolated as solids and were characterized by elemental analysis, mass spectrometry and IR, 1H NMR and 13C NMR spectroscopy. Recrystallization of the complexes from DMSO gave the compounds [Hg(MPytat)2]n (3a), [Hg(HMPytat)2Br2]·H2O (4a), [{Hg(HEPytat)(μ2-NS-EPytat)Cl2}2Hg] (6a), [Hg(EPytat)2]n (6b), [Hg(MPztat)2]n (10a) and [Hg(EPztat)2]n (11a) (HEPytat = 4-ethyl-5-pyridin-2-yl-2,4-dihydro-[1,2,4]triazole-5-thione and HEPztat = 4-ethyl-5-pyrazin-2-yl-2,4-dihydro-[1,2,4]triazole-5-thione). These complexes were studied by single-crystal X-ray diffraction. The structural analysis revealed the versatility of heterocyclic functionalized 1,2,4-triazole-5-thiones to coordinate to mercury(II) in the thione and thiolate forms through the use of various donor atoms to give different and interesting crystalline packings. The supramolecular assemblies observed in the solid state were analysed. These elegant assemblies are formed by a combination of several noncovalent interactions, including intermolecular hydrogen-bonding supramolecular synthons and aromatic–aromatic interactions. The short Hg⋯Hg distance of 3.660 A indicates the presence of a probable mercurophilic interaction in 6a.

New Pyrimidine‐2‐thiones from Reactions of Amidrazonethiols with 2‐Amino‐1,1,2‐ethenetricarbonitrile and Investigation of Their Antitumor Activity

Reactions of thiosemicarbazones with 2‐amino‐1,1,2‐ethenetricarbonitrile were reported. The reaction occurred in the amidrazonyl site, and new pyrimidine‐2‐thiones were obtained. The reaction mechanism was discussed. The structure of products was elucidated by MS, IR, and NMR spectra together with elemental analyses. The antitumor activity was evaluated against one tumor cell line. Using a standard MTT assay, the effect of the samples on the growth of HepG2 cells was investigated. Half of these compounds showed no cytotoxic effect on HepG2 cells, while the others result in decreasing in the HepG2 cell viability.

ChemInform Abstract: Synthesis of Thiazolidin‐4‐ones from Substituted (Ylidene)hydrazinecarbothioamides and Dimethyl Acetylenedicarboxylate.

AbstractThe reaction of thiosemicarbazones (I) with dimethyl acetylenedicarboxylate (II) to give thiazolidin‐4‐one derivatives (III) is reported (no yields given).

A novel series of thiosemicarbazone drugs: From synthesis to structure

A new series of thiosemicarbazones (TSCs) and their 1,3,4-thiadiazolines (TDZs) containing acetamide group have been synthesized from thiosemicarbazide compounds by the reaction of TSCs with cyclic ketones as well as aromatic aldehydes. The structures of newly synthesized 1,3,4-thiadiazole derivatives obtained by heterocyclization of the TSCs with acetic anhydride were experimentally characterized by spectral methods using IR, 1H NMR, 13C NMR and mass spectroscopic methods. Furthermore, the structural, thermodynamic, and electronic properties of the studied compounds were also studied theoretically by performing Density Functional Theory (DFT) to access reliable results to the experimental values. The molecular geometry, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) and Mulliken atomic charges of the studied compounds have been calculated at the B3LYP method and standard 6-31+G(d,p) basis set starting from optimized geometry. The theoretical 13C chemical shift results were also calculated using the gauge independent atomic orbital (GIAO) approach and their respective linear correlations were obtained.

Synthesis, Characterization, Electrochemical Studies, andIn VitroAntibacterial Activity of Novel Thiosemicarbazone and Its Cu(II), Ni(II), and Co(II) Complexes

Metal complexes were prepared by the reaction of thiosemicarbazone with CuCl2, NiCl2, CoCl2, Cu(OAc)2, Ni(OAc)2, and Co(OAc)2. The thiosemicarbazone coordinates to metal through the thionic sulfur and the azomethine nitrogen. The thiosemicarbazone was obtained by the thiosemicarbazide with 3-acetyl-2,5-dimethylthiophene. The identities of these compounds were elucidated by IR, 1H, 13C-NMR, and GC-MS spectroscopic methods and elemental analyses. The antibacterial activity of these compounds was first tested in vitro by the disc diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) was determined by using chloramphenicol as reference drug. The results showed that compound 1.1 is better inhibitor of both types of tested bacteria as compared to chloramphenicol.

ChemInform Abstract: Synthesis of N1,N3‐Disubstituted Formamidrazones via the TMSCI‐Promoted Reaction of Isocyanides with Thiosemicarbazones.

AbstractThe new Tms‐Cl‐promoted reaction of thiosemicarbazones with isocyanides provides access to diversely substituted formamidrazones.

Nickel complexes of some thiosemicarbazones: Synthesis, structure, catalytic properties and cytotoxicity studies

Reaction of salicylaldehyde thiosemicarbazone (H2L1), 2-hydroxyacetophenone thiosemicarbazone (H2L2) and 2-hydroxynaphthaldehyde thiosemicarbazone (H2L3) with Ni(ClO4)2·6H2O afforded dimeric complexes of type [{Ni(L)}2]. Reaction of these complexes with triphenylphosphine (PPh3), pyridine (py) and 4,4′-bipyridine (bpy) has yielded complexes of type [Ni(L)(PPh3)], [Ni(L)(py)] and [{Ni(L)}2(bpy)], respectively, which have also been obtained from reaction of the thiosemicarbazones with Ni(ClO4)2·6H2O and PPh3 or pyridine or 4,4′-bipyridine. Structures of the [{Ni(L)}2] complexes have been optimized by DFT calculations. Crystal structures of [Ni(L2)(PPh3)], [Ni(L2)(py)] and [{Ni(L1)}2(bpy)] have been determined. In all these complexes thiosemicarbazone is coordinated to nickel as ONS-donor. All these complexes show characteristic 1H NMR spectra and intense absorptions in the visible and ultraviolet region. Cyclic voltammetry on the complexes shows one irreversible oxidation on the positive side of SCE, and one irreversible reduction on the negative side. The mixed-ligand nickel complexes are found to be efficient catalysts for Heck type C–C coupling reactions. In vitro cytotoxicity screenings of the six mononuclear nickel complexes have been also carried out in a human tumor cell lines, viz. breast carcinoma cell line (MCF-7). [Ni(L3)(py)] shows the lowest LD50 value. An apoptosis study in MCF-7 with all the complexes confirms that at concentrations near LD50 they induce apoptosis.

ChemInform Abstract: Synthesis, Characterization and Antimicrobial Studies of Some New Pyrazole Incorporated Imidazole Derivatives.

AbstractTwo series of imidazoles are prepared: i) reaction of thiosemicarbazones (I) with dimethylacetylenedicarboxylate (II) furnishes the imidazoles (III) in good yields; ii) trisubstituted imidazoles (VI) are obtained by refluxing diketones (IV) with pyrazolecarbaldehydes (V) and ammonium acetate via Debus reaction.

Synthesis and in vitro evaluation of gold(I) thiosemicarbazone complexes for antimalarial activity

The reaction of thiosemicarbazones (TSCs) with [Au I(THT)Cl], THT = tetrahydrothiophene, has been investigated. The resulting gold(I) complexes have been characterized by a range of spectroscopic techniques: NMR spectroscopy, mass spectrometry, microanalysis and infrared spectroscopy. The in vitro antimalarial data for gold(I) TSC complexes suggests that coordination of gold(I) to TSCs enhanced their efficacy against the malaria parasite Plasmodium falciparum and their inhibition of the parasite cysteine protease falcipain-2.

P75NTR and pattern of invasion predict poor prognosis in oral squamous cell carcinomas

A new series of thiosemicarbazones (TSCs) and their 1,3,4-thiadiazolines (TDZs) containing acetamide group have been synthesized from thiosemicarbazide compounds by the reaction of TSCs with cyclic ketones as well as aromatic aldehydes. The structures of newly synthesized 1,3,4-thiadiazole derivatives obtained by heterocyclization of the TSCs with acetic anhydride were experimentally characterized by spectral methods using IR, 1H NMR, 13C NMR and mass spectroscopic methods. Furthermore, the structural, thermodynamic, and electronic properties of the studied compounds were also studied theoretically by performing Density Functional Theory (DFT) to access reliable results to the experimental values. The molecular geometry, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) and Mulliken atomic charges of the studied compounds have been calculated at the B3LYP method and standard 6-31+G(d,p) basis set starting from optimized geometry. The theoretical 13C chemical shift results were also calculated using the gauge independent atomic orbital (GIAO) approach and their respective linear correlations were obtained.

Synthesis, structure, spectroscopic properties and cytotoxic effect of some thiosemicarbazone complexes of palladium

Reaction of salicylaldehyde thiosemicarbazone (H2L1), 2-hydroxyacetophenone thiosemicarbazone (H2L2) and 2-hydroxynaphthaldehyde thiosemicarbazone (H2L3) (general abbreviation H2L, where H2 stands for the two dissociable protons, one phenolic proton and one hydrazinic proton) with Na2[PdCl4] affords a family of polymeric complexes of type [{Pd(L)}n]. Reaction of the polymeric species with two monodentate ligands (D), viz. triphenylphosphine (PPh3) and 4-picoline (pic), has yielded complexes of type [Pd(L)(D)]. These mixed-ligand complexes have also been obtained from reaction of the thiosemicarbazones with [Pd(PPh3)2Cl2] and [Pd(pic)2Cl2]. Crystal structures of [Pd(L1)(PPh3)] and [Pd(L2)(pic)] have been determined. The [Pd(L)(D)] complexes show characteristic 1H NMR spectra and intense absorptions in the visible and ultraviolet region. They also fluoresce in the visible region at ambient temperature. In vitro cytotoxicity screenings of the complexes along with four human clinical drugsviz.cisplatin, BCNU, 5-fluorouracil (5-FU) and hydroxyurea have been carried out in two human tumor cell lines, namely promyelocytic leukemia HL-60 and histiocytic lymphoma U-937. [Pd(L2)(PPh3)] shows the lowest IC50 value and is found to be much more cytotoxic than the reference anticancer drugs in both the cell lines. An apoptosis study in HL-60 with [Pd(L2)(PPh3)] confirms that at 10 µM concentration it induces apoptosis to a greater extent than cisplatin and camptothecin.

Synthesis, structure and spectroscopic properties of some thiosemicarbazone complexes of platinum

Reaction of salicyldehyde thosemicarbazone (H2L1), 2-hydroxyacetophenone thiosemicarbazone (H2L2) and 2-hydroxynapthaldehyde thiosemicarbazone (H2L3) (general abbreviation H2L, where H2 stands for the two dissociable protons, one phenolic proton and one hydrazinic proton) with K2[PtCl4] afforded a family of polymeric complexes of type [{Pt(L)}n]. Reaction of the polymeric species with two monodentate ligands (D), viz. triphenylphosphine (PPh3) and 4-picoline (pic), yielded complexes of the type [Pt(L)(D)]. These mixed-ligand complexes were also obtained from the reaction of the thiosemicarbazones with [Pt(PPh3)2Cl2] and [Pt(pic)2Cl2]. The crystal structure of [Pt(PPh3)(L2)] has been determined. The thiosemicarbazone ligands are coordinated, via dissociation of the two protons, as dianionic tridentate O,N,S-donors. The [Pt(L)(D)] complexes show characteristic 1H NMR spectra and intense absorptions in the visible and ultraviolet region. They also fluoresce in the visible region at ambient temperature.

Synthesis and Structure of Two Thiocarboxypyrazolic Acid Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reaction of Thiosemicarbazones from Heterocyclic Series with Acetic Anhydride.

AbstractFor Abstract see ChemInform Abstract in Full Text.