Thiosemicarbazide Moiety Research Articles

Synthesis and antibacterial evaluation of novel 1-(2,6-diethylphenyl)-5-oxopyrrolidine derivatives

Synthesis of 1-(2,6-diethylphenyl)-5-oxopyrrolidine derivatives containing hydrazone, semi/thiosemicarbazide and azole moieties is described. For this purpose, the appropriate hydrazide was treated with aromatic aldehydes, ketones and phenyl iso(thio)cyanates to obtain the desired outcome. The synthesized target compounds were evaluated for their antibacterial properties. The antibacterial screening revealed promising compounds with a pyrazole and thiosemicarbazide moieties in the molecule, which in some cases appeared to be 4 times more effective than Ampicillin.

Novel Isatin Thiosemicarbazone Derivatives as Potent Inhibitors of β-Amyloid Peptide Aggregation and Toxicity

Inhibition of β-amyloid peptide (Αβ) aggregation in Alzheimer's disease (AD) is among the therapeutic approaches against AD which still attracts scientific research interest. In the search for compounds that interact with Aβ and disrupt its typical aggregation course toward oligomeric or polymeric toxic assemblies, small organic molecules of natural origin, combining low molecular weight (necessary blood-brain barrier penetration) and low toxicity (necessary for pharmacological application), are greatly sought after. Isatin (1H-indoline-2,3-dione), a natural endogenous indole, and many of its derivatives exhibit a wide spectrum of neuropharmacological and chemotherapeutic properties. The synthesis and biological evaluation of four new isatins as inhibitors of Aβ aggregation is presented herein. In these derivatives, the N-phenyl thiosemicarbazide moiety is joined at the 3-oxo position of isatin through Schiff base formation, and substitutions are present at the indole nitrogen and position 5 of the isatin core. Biophysical studies employing circular dichroism, thioflavin T fluorescence assay, and transmission electron microscopy reveal the potential of the isatin thiosemicarbazones (ITSCs) to alter the course of Αβ aggregation, with two of the derivatives exhibiting outstanding inhibition of the aggregation process, preventing completely the formation of amyloid fibrils. Furthermore, in in vitro studies in primary neuronal cell cultures, the ITSCs were found to inhibit the Aβ-induced neurotoxicity and reactive oxygen species production at concentrations as low as 1 μM. Taken all together, the novel ITSCs can be considered as privileged structures for further development as potential AD therapeutics.

Design and Synthesis of Novel 1-substituted-3-(3-(3-nitrophenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-yl amino) Isothioureas for their Anti-HIV, Antibacterial Activities, Graph Theoretical Analysis, Insilico Modeling, Prediction of Toxicity and Metabolic Studies.

In the present study, we have placed the substituted thiosemicarbazide moiety at the C-2 position and 3-nitrophenyl group at N-3 position of benzopyrimidines and studied their antitubercular, anti-HIV and antibacterial activities against selected gram positive and negative bacteria. The target compounds 1-substituted-3-(3-(3-nitrophenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-ylamino) isothioureas (PTS1 - PTS15: ) were obtained by the reaction of 2-hydrazino-3-(3-nitrophenyl) benzopyrimidin-4(3 H)-one (5: ) with different alkyl/aryl isothiocyanates followed by methylation with dimethyl sulphate. All synthesized compounds were screened for their antitubercular, anti-HIV and antibacterial activity against selective gram positive and gram negative bacteria by agar dilution method. Among the series, compound 2-methyl-3-(3-(3-nitrophenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-ylamino)-1-(3-chlorophenyl)isothiourea (PTS14): shown most potent activity against Klebsiella pneumoniae, Proteus vulgaris and Staphylococcus aureus; PTS14: exhibited the antitubercular activity at the minimum microgram of 1.56 µg/mL and anti-HIV activity at 0.96 µg/mL against HIV1 and HIV2 and offers potential for further optimization and development to new antitubercular and anti-HIV agents. The results obtained from this study confirm that the synthesized and biologically evaluated benzopyrimidines showed promising antimicrobial, antitubercular and anti-HIV activities and are new scaffolds for antimicrobial activity.

Polymer‐anchored mononuclear and binuclear CuII Schiff‐base complexes: Impact of heterogenization on liquid phase catalytic oxidation of a series of alkenes

Liquid phase catalytic oxidation of a number of alkenes, for example, cyclohexene, cis‐cyclooctene, styrene, 1‐methyl cyclohexene and 1‐hexene, was performed using polymer‐anchored copper (II) complexes PS‐[Cu (sal‐sch)Cl] (5), PS‐[Cu (sal‐tch)Cl] (6), PS‐[CH2{Cu (sal‐sch)Cl}2] (7) and PS‐[CH2{Cu (sal‐tch)Cl}2] (8). Neat complexes [Cu (sal‐sch)Cl] (1), [Cu (sal‐tch)Cl] (2), [CH2{Cu (sal‐sch)Cl}2] (3) and [CH2{Cu (sal‐tch)Cl}2] (4) were isolated by reacting CuCl2·2H2O with [Hsal‐sch] (I), [Hsal‐tch] (II), [H2bissal‐sch] (III) and [H2bissal‐tch] (IV), respectively, in refluxing methanol. Complexes 1–4 have been covalently anchored in Merrifield resin through the amine nitrogen of the semicarbazide or thiosemicarbazide moiety. A number of analytical, spectroscopic and thermal techniques, such as CHNS analysis, Fourier transform‐infrared, UV–Vis, PMR, 13C‐NMR, electron paramagnetic resonance, scanning electron microscopy, energy‐dispersive X‐ray analysis, thermogravimetric analysis, atomic force microscopy, atomic absorption spectroscopy, and electrospray ionization‐mass spectrometry, were used to analyze and establish the molecular structure of the ligands (I)–(IV) and complexes (1)–(8) in solid state as well as in solution state. Grafted complexes 5–8 were employed as active catalysts for the oxidation of a series of alkenes in the presence of hydrogen peroxide. Copper hydroperoxo species ([CuIII (sal‐sch)‐O‐O‐H]), which is believed to be the active intermediate, generated during the catalytic oxidation of alkenes, are identified. It was found that supported catalysts are very economical, green and efficient in contrast to their neat complexes as well as most of the recently reported heterogeneous catalysts.

New thiosemicarbazide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors: Design, synthesis, and biological evaluation

A new series of thiosemicarbazide-1,2,3-triazole hybrids 10a-o has been synthesized, characterized by 1H NMR, 13C NMR, and screened for their in vitro α-glucosidase inhibitory activity. All of the synthesized compounds displayed excellent α-glucosidase inhibitory activity with IC50 values in the range of 75.0 ± 0.5 to 253.0 ± 0.5 μM, as compared to the standard drug acarbose (IC50 = 750.0 ± 1.5 μM). Among the synthesized compounds, compound 10h (IC50 = 75.0 ± 0.5) with 4-methoxy group at phenyl part of thiosemicarbazide moiety and 2,6-dichloro substituents at benzyl moiety was found to be the most potent compound. Kinetic analysis revealed that compound 10h is a competitive inhibitor for α-glucosidase. Docking study of compound 10h in the active site of α-glucosidase showed that this compound interacted with residues His239, His279, Glu304, Gly306, and Arg312.

Turn-On Fluorescence Probe for Nitric Oxide Detection and Bioimaging in Live Cells and Zebrafish.

An effective bioanalytical method for rapid, sensitive, specific, and in situ sensing of nitric oxide (NO) is the key for further unveiling the biological functions of this gasotransmitter molecule in vitro and in vivo. In this contribution, a new fluorescence probe for sensing and imaging of NO in live systems was developed. The probe, FP-NO, was designed by exploring a novel sensing mechanism, i.e., the rotation of the N-N single bond of a coumarin derivative. FP-NO was prepared by incorporating a recognition unit, thiosemicarbazide moiety into a coumarin fluorophore. The weakly fluorescent FP-NO quickly and selectively reacts with NO to form a highly fluorescent product, FP-P. Such an enhancement of fluorescence emission allows NO detection with high sensitivity. The detection limit was 47.6 nM. The reaction mechanism was validated by HRMS titration analysis and the "OFF-ON" fluorescence response mechanism was rationalized by theoretical computation. FP-NO is biocompatible and live cell membrane permeable. The feasibility of FP-NO as the fluorescence probe for imaging and flow cytometry analysis of exogenous NO in MCF-7 cells and exogenous NO production in inflamed J774A.1 macrophage cells was then evaluated. Visualization of exogenous and endogenous NO production in live zebrafish was then achieved, implying the potential application of FP-NO in the studies of the NO roles in live organisms.

The Antiproliferative Activity and Molecular Docking studies of some sulfonamides against cancer cell lines compared to normal cells

Some new and known substituted 1,2,3,4-tetrahydroacridines incorporated at their position nine with various sulfa drug or thiosemicarbazide moieties were synthesized. Biologically, these compounds were investigated for their antiproliferative activity against human breast cancer (MCF-7) cell line compared to murine fibroblast normal cell line (BALB/3T3). The results were calculated as the IC50 (inhibitory concentration 50%) compared with Cisplatin as control. Furthermore, a docking simulation study was carried out to predict the inhibitory mode of action of the most active compounds.

3-Acetyl-8-methoxy-2[H]-chromen-2-one derived Schiff bases as potent antiproliferative agents: Insight into the influence of 4(N)-substituents on the in vitro biological activity

A series of 3-acetyl-8-methoxycoumarin appended thiosemicarbazones (1–4) was prepared from the reaction of 3-acetyl-8-methoxycoumarin with 4(N)-substituted thiosemicarbazides in a view of ascertaining their biological properties with the change of N-terminal substitution in the thiosemicarbazide moiety. Comprehensive characterization was brought about by various spectral and analytical methods. The molecular structures of all the compounds were determined by single crystal X-ray diffraction analysis. Binding studies with Calf thymus DNA (CT-DNA) and proteins such as Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA) indicated an intercalative mode of binding with DNA and static quenching mechanism with proteins. The compounds cleaved plasmid DNA (pBR322) and acted well as free radical scavengers. A good spectrum of antimicrobial activity was observed against four bacterial and five fungal pathogens. The compounds exhibited profound antiproliferative activity on MCF-7 (human breast cancer) and A549 (human lung carcinoma) cell lines. Assay on human normal keratinocyte cell line HaCaT showed that the compounds were non-toxic to normal cells.

Photophysical and DFT Studies of Cationic Ag(I) Complexes with Thiosemicarbazides Derived from p‐Toluenesulfohydrazide

AbstractReactions of p‐toluenesulfohydrazide with R‐isothiocyanates afford new ligands containing both the sulfonamide and thiosemicarbazide moieties (LR: R=cyclohexyl (Cy) or phenyl (Ph)). LR reacts with AgNO3 in EtOH in a 2:1 M ratio leading to formation of colourless Ag(I) complexes of general formula [Ag(LR)2]NO3. The crystal structure of a representative complex was determined by crystallographic studies and shows the Ag(I) coordinated by two thiosemicarbazide ligands in a S‐monodentate coordination mode along with a significant interaction with a nitrate counter‐ion in a bent geometry. Photophysical studies show that both the free ligands and complexes are essentially non‐luminescent at room temperature. At 77 K and glassy media, the silver complexes exhibit a luminescence band in the visible‐light region. Besides, experimental and theoretical analyses suggest the population of the triplet state of these complexes after electronic excitation at around 250 nm. Overall, it was verified that the observed emission of the Ag(I) complexes can be attributed to 3MLCT radiative decay and that the silver complex with LPh shows a higher intensity emission than the complex with LCy.

Design, synthesis and in vitro biological evaluation of novel [1,2,3]triazolo[4,5-d]pyrimidine derivatives containing a thiosemicarbazide moiety

A series of hybrid molecules containing [1,2,3]triazolo[4,5-d]pyrimidine and thiosemicarbazide moieties were designed, synthesized and evaluated for their antiproliferative activities against MGC-803, NCI-H1650 and PC-3 human cancer cells. Some of the synthesized compounds showed moderate to good activity against three selected cancer cell lines. Among these compounds, compound 29 displayed the most potent antiproliferative activity as well as good selectivity between cancer cells and normal cells. Further mechanism studies revealed that compound 29 could obviously inhibit the colony formation and migration of MGC-803 as well as induced apoptosis.

Synthesis and Electrical Conductivity of N-(3-(Trifluoromethyl)Benzylidine)Thiosemicarbazide towards Dyes Sensitized Solar Cell

Organic compound containing thiosemicarbazide moiety has been successfully synthesized. The new synthesized dyes, N-(3-(Trifluoromethylbenzaldehyde)benzylidine thiosemi- carbazide (3-TFT) was characterized by spectroscopic technique namely, CHNS elemental analysis, Fourier Transform Infra-Red analysis (FT-IR), UV-Visible analysis (UV-Vis),1H and13C Nuclear Magnetic Resonance (NMR). The thin films of this dye have been prepared using a spin coating technique and deposited on indium tin oxide (ITO) glass substrate. The main highlight was an electrical conductivity of thin films which was measured using four point probing system in a range of light intensity, 25 Wm-2until 200Wm-2. The potential electrical conductivity of 3-TFT dye was found gradually increased until reached the maximum conductivity values of 0.1489 Scm-1at light intensity of 100 Wm-2in the most diluted concentration at 1x10-5M.

Synthesis and analysis of photonic crystal and Zn(II) complex bearing thiosemicarbazide moiety

Photonic crystal (PhCs) has versatile properties with potential to enhance solar cell application. Nanoparticles of poly (methyl methacrylate) (PMMA) have been successfully prepared by green-chemistry approach where no surfactant, cross linking agent and solvent was involved. Introducing of acid hydrolysed TEOS in PhCs boost of numerous fascinating approaches to the enhancement PhCs backbone. Incorporated of metal complex such as zinc(II) complexes were prepared by refluxing in PhCs improved characteristic of solar cells application because of high photocatalytic activity. The experimental results suggest that involving localised surface plasmon resonance (LSPR) properties from excellent plasmonic nanoparticles such gold, silver or the alloy (gold and silver) would enhanced light trapping performance as expressed by properties. The composite inverse photonic crystal was characterised by using FTIR and SEM-EDS.

Synthesis and analysis of photonic crystal and Zn(II) complex bearing thiosemicarbazide moiety

Photonic crystal (PhCs) has versatile properties with potential to enhance solar cell application. Nanoparticles of poly (methyl methacrylate) (PMMA) have been successfully prepared by green-chemistry approach where no surfactant, cross linking agent and solvent was involved. Introducing of acid hydrolysed TEOS in PhCs boost of numerous fascinating approaches to the enhancement PhCs backbone. Incorporated of metal complex such as zinc(II) complexes were prepared by refluxing in PhCs improved characteristic of solar cells application because of high photocatalytic activity. The experimental results suggest that involving localised surface plasmon resonance (LSPR) properties from excellent plasmonic nanoparticles such gold, silver or the alloy (gold and silver) would enhanced light trapping performance as expressed by properties. The composite inverse photonic crystal was characterised by using FTIR and SEM-EDS.

Assessment of 5-substituted Isatin as Surface Recognition Group: Design, Synthesis, and Antiproliferative Evaluation of Hydroxamates as Novel Histone Deacetylase Inhibitors

Histone deacetylase (HDAC) is a promising target for cancer treatment. HDAC inhibitors consist of three pharmacophoric features: an aromatic cap group, zinc binding group (ZBG), and a linker chain connecting cap group to ZBG. Herein, we report on (i) substituted isatin moiety as the cap group that recognizes the surface of active enzyme pocket and (ii) thiosemicarbazide moiety incorporated as linker group responsible for connecting the cap group to ZBG (hydroxamic acid). The synthesized compounds were evaluated for their antiproliferative activity and HDAC enzyme inhibition. The binding mode analysis of proposed compounds was evaluated by docking studies. Several analogs were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells, with GI50 values in the micromolar range. One compound (Vd) was found to have greater in vitro antiproliferative activity in comparison to other compounds.

Inhibitory effect of coumarin derivatives on apple (cv. Idared) polyphenol oxidase

Inhibitory effect of 32 coumarin derivatives (20 Schiff bases, 5 thiosemicarbazides, 5 thiazolidinones, and their precursors, 7- hydroxy-4-methylcoumarin and 4-methylcoumarin- 7-yl hydrazine carboxylate) on partially purified apple polyphenol oxidase was investigated. Thirteen coumarin derivatives inhibited polyphenol oxidase (5 Schiff bases, 5 thiosemicarbazides, 1 thiazolidinone, 4-methyl- 7-hydroxycoumarin and 4-methylcoumarin-7-yl hydrazine carboxylate), while 19 derivatives showed no effect on enzyme activity. The most effective inhibitors were thiosemicarbazides, with 4-methyl-1-(2-(4-methyl-2-oxo-2H-chromen- 7-yloxy)acetyl) thiosemicarbazide (compound C23) being the most prominent inhibitor (IC50 = 10.45 µM). The importance of thiosemicarbazide moiety as crucial structure element for strong apple PPO inhibition was confirmed by its cyclisation to thiazolidinone bearing the same substituents as corresponding thiosemicarbazide. Capture of the sulphur atom of thiosemicarbazide group within tiazolidinone ring caused significant loss of inhibitory effect against apple PPO.

A Smart Molecule for Selective Sensing of Nitric Oxide: Conversion of NO to HSNO; Relevance of Biological HSNO Formation.

A smart molecule, QT490, containing thiosemicarbazide moiety acts as a highly selective turn-on in vitro NO sensor through the unprecedented NO-induced transformation of thiosemicarbazide moiety to 1,3,4-oxadiazole heterocycle with the concomitant release of HSNO, thereby eliminating any interference from various endogenous biomolecules including dehydroascorbic acid, ascorbic acid, etc. The kinetic studies of the reactions between QT490 and NO provide a mechanistic insight into formation of HSNO/RSNO from the reaction between H2S/RSH and NO in the biological system. This novel probe is non-cytotoxic, cell permeable, water-soluble, and appropriate for intracellular cytoplasmic NO sensing with the possibilities of in vivo applications.

A highly sensitive and selective colorimetric and off–on fluorescent chemosensor for Cu2+ based on rhodamine 6G hydrazide bearing thiosemicarbazide moiety

Abstract A rhodamine derivative (R1) has been synthesized by an additive reaction of rhodamine 6G hydrazide with methyl 2-isothiocyanatobenzoate, which exhibits high selectivity and sensitivity as a fluorescent sensor toward Cu2+ under physiological conditions. The detection limit of Cu2+ ion is 47.2 nM. Moreover, R1 could sense Cu2+ by “naked eye” with a color change from colorless to pink. This selective signaling behavior is not affected by other canions that might be present in the environmental samples. The application of the fluorescent sensor in monitoring intracellular Cu2+ in HeLa cells was also demonstrated.

Colorimetric Naphthalene‐Based Thiosemicarbazide Anion Chemosensors with an Internal Charge Transfer Mechanism

A series of thiosemicarbazide anion chemosensors substituted with naphthalene and 4‐nitrophenyl or phenyl units were synthesized. The molecules were characterized by using 1H,13C DEPT and 15N NMR spectroscopy. The anion binding properties of compounds 1–4 were investigated by UV/Vis absorption and fluorescence spectroscopy in DMSO, DMSO/H2O (9:1 v/v), and acetonitrile with hydroxide, fluoride, acetate, hypophosphate, and chloride anions. Striking color changes were observed with nitro‐containing chemosensors 2–4 with all anions, with the exception of chloride, which was attributed to an internal charge‐transfer mechanism. 1H/13C/15N NMR titration studies and DFT and charge distribution calculations support a mechanism involving deprotonation of the central N–H bond. Compound 4 with a methylene spacer between the naphthalene and thiosemicarbazide moieties was deliberately designed as a fluorescent photoinduced electron‐transfer anion (PET) sensor. However, the methylene spacer did not prevent delocalization of the HOMO orbital between the planar aromatic ring and the thiosemicarbazide unit as expected on the basis of the “fluorophore–spacer–receptor” PET model.

Spectra-structure correlation based study of complex molecules of 1-isonicotinoyl-3-thiosemicarbazide with Ni2+, Mn2+ and Fe3+ using Raman, UV–visible and DFT techniques

In present work, we have analysed the structural property of newly synthesized ligand and its coordination complex molecules with Ni2+, Mn2+ and Fe3+. The spectroscopic techniques UV–visible, IR, Raman and DFT methods are used. The newly synthesized ligand 1-isonicotinoyl-3-thiosemicarbazide (Hintsc) has supramolecular architecture stabilized through various intermolecular interactions viz. NH⋯O, CH⋯O, CH⋯N, NH⋯S and CH⋯S type hydrogen bonds as observed in the single crystal of the ligand. The single crystals of the complexes could not be obtained with high degree of homogeneity from the solutions therefore plausible geometry of the complexes have been proposed on the basis of Raman spectroscopy, UV–visible and DFT methods and coordination properties of Ni2+, Mn2+ and Fe3+ with ligand (Hintsc). The ligand Hintsc contains the thiosemicarbazide (TSC) moiety through which Ni2+, Mn2+ and Fe3+ metals are coordinated. Raman spectroscopy is used to investigate the binding of Ni2+, Mn2+ and Fe3+ with ligand (Hintsc). In Raman spectra, the disappearance of NH bending/ NH stretching and lower wavenumber region Raman spectra clearly confirms that Ni2+ and Mn2+ metals are coordinated through N3 and O sites of thiosemicarbazide (TSC) and consequently formed the chelate ring {C6N2N3MO}, where M Ni2+ and Mn2+. In Fe complex, Fe3+ is coordinated through N2 and S sites of TSC and formed the chelate ring {C7N3N2FeS}. The structural and molecular property of 1-isonicotinoyl-3-thiosemicarbazide (Hintsc) and its complexes with transition metals Ni2+, Mn2+, Fe3+ have also been studied by DFT technique. By means of UV–visible, Raman spectroscopy and DFT technique, it is found that Ni2+, Mn2+ and Fe3+ exhibit the octahedral coordination property with 1-isonicotinoyl-3-thiosemicarbazide (Hintsc).

Antimicrobial activities of some synthesized 1-(3-(2-methylphenyl)-4-Oxo-3H-quinazolin-2-yl-4-(substituted)thiosemicarbazide derivatives

The substituted thiosemicarbazide moiety was placed at the C-2 position and 2-methylphenyl group at N-3 position of quinazoline ring and obtained compounds were tested for their antitubercular activities and antibacterial activities against selected gram-positive and gram-negative bacteria. The target compounds 1-(3-(2-methylphenyl)-4-oxo-3H-quinazolin-2-yl)-4-(substituted) thiosemicarbazides were obtained by the reaction of 2-hydrazino-3-(2-methylphenyl) quinazolin-4(3H)-one with different dithiocarbamic acid methyl ester derivatives. All synthesized compounds were also screened for their antimicrobial activity against selective gram-positive and gram-negative bacteria by agar dilution method. Among the series, 1-[3-(2-methylphenyl)-4-oxo-3H-quinazolin-2-yl]-4-[4-chlorophenyl]-thiosemicarbazide exhibited the most potent activity against S. typhi, E. coli, and B. subtilis, while 1-[3-(2-methylphenyl)-4-oxo-3H-quinazolin-2-yl]-4-[4-nitrophenyl]-thiosemicarbazide was the most potent against E. coli, B. subtilis, P. aeruginosa, S. typhi, and S. flexneri. These two compounds exhibited the antitubercular activity at the minimum concentration (3 μg/mL) that offered potential for further optimization and development of new antitubercular agents. The obtained results demonstrated promising antimicrobial and antitubercular activities of the synthesized quinazoline compounds which could be used as new scaffolds for improving their antimicrobial activity.