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Various benzotriazepine ring systems have been synthesized and examined for biological activity. Moreover, the 1,3,4-benzotriazepin-2-one has been shown to act as a constrained amino amide surrogate in mimics of peptide turn secondary structures. This review examines syntheses of the different benzotriazepine ring systems and heterocycle fused variants as well as their conformational and biological properties. [ABSTRACT FROM AUTHOR]

To develop a green nanomaterial for specialty applications, spherical nanocellulose (SNC) was functionalized to a semicarbazone‐Schiff base via a polymer analogous reaction. Firstly, SNC was synthesized from cellulose extracted from huge forest biomass, pine needles (PNs). The glucopyranose ring of SNC was oxidatively cleaved at C2–C3 to form SNC‐dialdehyde (SNC‐DA) by periodate oxidation. Both the aldehydic groups generated were reacted with semicarbazide to form a semicarbazone‐Schiff base, referred to as functional spherical nanocellulose (FSNC). All the materials synthesized were characterized by FTIR, FESEM, EDS, TEM, and XRD studies. The FSNC was evaluated as an adsorbent for Hg2+ ions. The adsorption adhered to pseudo‐second order kinetics and Langmuir adsorption isotherm having a maximum adsorption capacity/Lungmuir adsorption capacity of 172.412 mg/g at 60 min. The selectivity of FSNC for Hg2+ ions was confirmed from its appreciable removal (82%) from solution in tap water and 70% with other metal ions. FSNC exhibited bifunctional nature as it possesses antimicrobial activity against bacteria, that is, Gram (+) (Bacillus aereus) and Gram (−) (Escherichia coli and Salmonella typhi), and a fungus Byssochlamys fulva. FSNC showed good recyclability up to eight sorption–desorption cycles. Thus, we have valorized biomass into an eco‐friendly and low‐cost bifunctional material as an adsorbent for Hg2+ ions cum antimicrobial agent. Highlights: Spherical nanocellulose (SNC) prepared via acidic hydrolysis from pine needlesSNC functionalized to semicarbazone‐based bifunctional Schiff baseThe Schiff base is a rapid and efficient Hg2+ ions adsorbentThe Schiff base has good antimicrobial activities against Gram (−) bacteriaBiowaste‐based adsorbent has the potential to sustain the bio‐circular economy [ABSTRACT FROM AUTHOR]

Thiosemicarbazones constitute a class of organic compounds with the general structure R=N-NH-CS-NHR and are known for their biological properties, making them an important structure for drug development. This work presents a systematic review of the main publications from the last decade (2013–2023) reporting the leishmanicidal potential of thiosemicarbazones. A search was conducted in three databases: Web of Science, Science Direct, and SciFinder, using the following singular English descriptors, ‘thiosemicarbazone’ and ‘leishmanicidal.’ During the selection process, 25 articles were identified, 12 were excluded due to duplication, and 5 were excluded for not meeting the pre-defined inclusion criteria. As a result, 8 articles were selected for discussion in this systematic review. In the reviewed studies, 118 thiosemicarbazones were synthesized and tested in vitro for their activity against protozoa of the Leishmania genus. In three of these studies, researchers identified thiosemicarbazones with promising results and chose to go deeper into their investigation. Given the significant leishmanicidal activity observed in thiosemicarbazones studied over the past 10 years, coupled with the scarcity of publications – less than one article per year – it is evident that this represents a promising research field.

A series of new (thio)semicarbazones containing adamantane and 3,7-dimethyloctyl fragments was synthesized. The configuration of imine bond was proposed based on the characteristic signals of 1Н and 13С NMR spectra simulated by quantum-chemical calculations. [ABSTRACT FROM AUTHOR]

The ligand ((E)-((2-hydroxynaphthalen-1-yl)methylidene)amino)urea (HL) and its Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes have been synthesized and characterized by conventional spectroscopic methods, elemental analysis, molar conductivity, and thermal analysis. The complexes show that the ligand disposes of as tridentate anionic (ONO) donor via deprotonated (OH)ring, (C = N)azomethine, and (C = O) functions with a ratio of metal:ligand (1:2) with Mn(II) and Co(II) ions. While, in Ni(II), Cu(II), and Zn(II) complexes, HL acts as monobasic bidentate (NO) donor ligates through deprotonated (OH)ring and (C = N)azomethine with metal:ligand of 1:2. Zn(II) complex adopts tetrahedral and other complexes adopt octahedral geometry. DFT in the material studio package validates the geometry of ligand and metal complexes by measuring bond lengths and angles, HOMO, and LUMO. The thermodynamic and kinetic parameters were estimated from TGA-DTG curves. These complexes provide better activities against human prostatic cell line PC-3 than free ligand which is further verified by molecular docking studies. 3D and 2D molecular interaction of ligand, HL to inhibitory activity to the 2Q7I protein. Highlights: Synthesis of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes of ligand (HL). Elemental analysis, molar conductivity, spectral methods (IR, UV-Vis., ESR, mass, and 1H NMR). The kinetic thermodynamic parameters (ΔE, ΔH, ΔS, and ΔG) are estimated from the TGA-DTG curves. Complexes provide better activities against human prostatic cell line PC-3 than the free ligand. Molecular docking of ligand and complexes with the receptor of prostate cancer (H874Y) hormone. [ABSTRACT FROM AUTHOR]

New Zn(II), Cd(II), VO(IV), and UO2(VI) solvatochromic complexes derived from 6‐ethyl‐4‐hydroxy‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carboxaldehyde‐semicarbazone ligand (H2L) were synthesized and established by elemental analyses, spectral (IR, UV, NMR, mass spectra), molar conductivity measurements, magnetic susceptibility, and thermal gravimetric analysis (TGA). The ligand coordinates with metal ions through ONO chelating sites, forming an octahedral geometry arrangement, except UO2(VI) that showed pentagonal bipyramidal geometry. Using Coats–Redfern methodology, the kinetic parameters (Ea, A, ΔH, ΔS, and ΔG) of the thermal decomposition steps were calculated and discussed. The complexes showed solvatochromic behavior that used to estimate the ground and excited state dipole moments. Optimization and structural parameters were carried out by density function theory (DFT) at B3LYP/GENECP method at 6‐311G(d,p) basis set for C, H, N, and O atoms and SDD (Stuttgart/Dresden) basis set for the metal atoms and interrelated with the experimental results. The complexes were tested for antimicrobial efficiency against Gram‐positive bacteria, Gram‐negative bacteria, yeast, and fungi. Also, antitumor activity was investigated against HepG‐2 cell line. Finally, the new synthesized complexes upon subjecting to molecular docking and distinguishable results showed outstanding inhibition results of VEGFR‐2 via achieving a high stabilization level inside the largest pocket of 1YWN protein. [ABSTRACT FROM AUTHOR]

The rapid development of resistance by ureolytic bacteria which are involved in various life-threatening conditions such as gastric and duodenal cancer has induced the need to develop a new line of therapy which has anti-urease activity. A series of pyridine carboxamide and carbothioamide derivatives which also have some novel structures were synthesized via condensation reaction and investigated against urease for their inhibitory action. Among the series, 5-chloropyridine-2 yl-methylene hydrazine carbothioamide (Rx-6) and pyridine 2-yl-methylene hydrazine carboxamide (Rx-7) IC50 = 1.07 ± 0.043 µM, 2.18 ± 0.058 µM both possessed significant activity. Furthermore, molecular docking and kinetic studies were performed for the most potent inhibitors to demonstrate the binding mode of the active pyridine carbothioamide with the enzyme urease and its mode of interaction. The ADME profile also showed that all the synthesized molecules present oral bioavailability and high GI absorption. [ABSTRACT FROM AUTHOR]

A novel semicarbazone NO2 ligand, H2L, was synthesized. The ligand reacted with several metal ions such as Cu(II), Ni(II), Co(II), Fe(III), Cr(III), and Mn(II) in a molar ratio 1:1 (M:L). The H2L ligand and its metal complexes were characterized by electronic, infrared, mass, nuclear magnetic resonance, electron spin resonance spectra, as well as elemental analysis, thermal analysis, molar conductance, and magnetic susceptibility measurements. The Coats–Redfern equations were used to calculate the kinetic parameters (Ea, A, ΔH, ΔS, and ΔG) of the thermal decomposition stages. The H2L ligand acts as dianionic NO2 tridentate in all complexes and coordinates through enolate oxygen, azomethine nitrogen, and deprotonated OH group. The geometrical arrangements in all metal complexes were octahedral geometries. Based on density functional theory (DFT) level implemented in the Gaussian 09 program at B3LYP/6‐311G(d,p) level, the molecular structural parameters of the ligand and its metal complexes were calculated, and the theoretical data were connected with the experimental results. The antimicrobial activity of the current compounds was examined against Gram‐positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram‐negative bacteria (Salmonella typhimurium and Escherichia coli), yeast (Candida albicans), and fungus (Aspergillus fumigatus). The antitumor activity of the ligand and its metal complexes was investigated against HepG2 cell line, which revealed promising IC50 values comparable with that of Cis‐platin. All synthesized compounds were also subjected to molecular docking studies to investigate their binding pattern and affinity for the VEGFR‐2 active site and correlated with antitumor data. [ABSTRACT FROM AUTHOR]

A series of novel 2-(substituted arylidene)-N-(5-(propylthio)-2,3-dihydro-1H-benzo[d]imidazol-2-yl)hydrazine-1-carboxamide derivatives 3a-i were synthesized via condensation of N-(5-(propylthio)-1H-benzo[d]imidazol-2-yl) hydrazinecarboxamide (2), with the corresponding ketone or aldehydes. The chemical structures of the compounds prepared were confirmed by analytical and spectral data. The compounds were screened for their a-glucosidase inhibitory activity and all of them showed better inhibition than acarbose, except 3h. In particular, compound 3a proved to be the most active compound among all synthetic derivatives having IC50 value 12.88 ± 0.98 µM. Also, molecular docking studies were carried out for the compounds to figure out the binding interactions. Compound 3a has exhibited the highest binding energy (ΔG = -9.4 kcal/mol) and the most hydrogen bond interactions with active sites. Eventually, in silico studies were in good agreement with in vitro studies. [ABSTRACT FROM AUTHOR]

Neutral and cationic copper(II) semicarbazone complexes with perfluoroalkyl carboxylates as ligands or counter anions, respectively, were synthesized. The lipophilicity and cytotoxicity of these compounds were determined. The cationic complexes with perfluoroalkyl carboxylate anions are more cytotoxic towards MOLT-4 cells compared to their nitrate analogue. [Display omitted] • Eight novel copper(II) semicarbazone perfluoroalkyl carboxylates were synthesized. • Lipophilicity and cytotoxicity of these compounds were determined. • Lipophilic anions enhance cytotoxicity of cationic copper semicarbazone complexes. • Facile deprotonation of hydrazonic nitrogen of coordinated semicarbazone by acetate. A series of (2,4-dihydroxybenzaldehyde dibenzyl semicarbazone) perfluoroalkyl carboxylato copper(II) complexes, [CF 3 (CF 2) n CO 2 (LH)Cu] (LH 2 = 2,4-dihydroxybenzaldehyde dibenzyl semicarbazone; n = 0, 2, 4, 6; 1–4), and (2,4-dihydroxybenzaldehyde dibenzyl semicarbazone) pyridine copper(II) perfluoroalkyl carboxylates, [(LH)(py)Cu]+[CF 3 (CF 2) n CO 2 ]− (5–8) were synthesized. The lipophilicity of these compounds was determined by reverse-phase thin layer chromatography and correlated with their cytotoxicity towards MOLT-4 human leukaemia cells. Cytotoxicity is more strongly correlated with lipophilicity for the non-ionic compounds (1–4) than for the ionic compounds (5–8). Compounds 5–8 (IC 50 2.8–3.8 μM) are generally more cytotoxic than compounds 1–4 (IC 50 3.6–8.4 μM). They also exhibit slightly higher cytotoxicity than the parent anticancer compound [(LH)(py)Cu]+[NO 3 ]− (IC 50 4.15 μM), suggesting that it is possible to enhance the cytotoxicity of [(LH)(py)Cu]+[NO 3 ]− by replacing nitrate with anions of higher lipophilicity. Attempts to synthesize the non-fluorinated analogue [(LH)(py)Cu]+[CH 3 CO 2 ]− resulted in the formation of the deprotonated complex [L(py)Cu], whose structure was confirmed by X-ray crystallography. The structural parameters indicate that the deprotonation site is the hydrazonic nitrogen of the semicarbazone ligand. [ABSTRACT FROM AUTHOR]

Most breast and prostate cancers are caused by abnormal production or action of steroidal hormones. Hormonal drugs based on steroid scaffolds represent a significant class of chemotherapeutics that are routinely used in chemotherapy. In this study, the synthesis of new 17a-homo lactone and 17α-(pyridine-2-ylmethyl) androstane derivatives with hydrazide and semicarbazone motifs is presented. All compounds were screened for their effect on cell viability against a panel of five cancer cell lines and one healthy cell line. Two compounds showed significant cytotoxicity against cancer cells, with low toxicity against healthy cells. The relative binding affinities of compounds for the ligand-binding domains of estrogen receptor α, estrogen receptor β, androgen receptor and glucocorticoid receptor were tested using a fluorescence screen in yeast. Potential for inhibition of aldo-keto reductase 1C3 and 1C4 activity was measured in vitro. Experimental results are analyzed in the context of molecular docking simulations. Our results could help guide design of steroid compounds with improved anticancer properties against androgen- and estrogen-dependent cancers. [Display omitted] • New androstane hydrazides and semicarbazones were synthesized. • One benzohydrazide and one hydrazine-1-carbothioamide derivative were cytotoxic. • Five compounds were identified as selective inhibitors of AKR1C3. • One acetohydrazide and one hydrazine-1-carboxamide were potent inhibitors of AKR1C4. • In silico studies support experimentally confirmed protein-ligand interactions. [ABSTRACT FROM AUTHOR]

Thirty semicarbazone and thiosemicarbazone derivatives (2a–w and 4a–g) from chalcones containing furan and thiophene ring were designed and synthesized. They were characterized by IR, 1H NMR, 13C NMR and HRMS. The crystal structure of compound 2r was characterized by single crystal X-ray diffraction. It crystallizes in the monoclinic system with space group P21/c. The insecticidal activity of the synthesized compounds was screened against Leucania separata and Pieris rapae using beta-cypermethrin as the comparative standard. The results displayed that most of them had remarkable insecticidal activity. Among them, compounds 2e–g showed better activity than beta-cypermethrin against L. separata and P. rapae. Compound 2p also possessed a better activity than beta-cypermethrin against P. rapae. The insecticidal activities of these compounds have been reported for the first time. [ABSTRACT FROM AUTHOR]

The rapid development of resistance by ureolytic bacteria which are involved in various life-threatening conditions such as gastric and duodenal cancer has induced the need to develop a new line of therapy which has anti-urease activity. A series of pyridine carboxamide and carbothioamide derivatives which also have some novel structures were synthesized via condensation reaction and investigated against urease for their inhibitory action. Among the series, 5-chloropyridine-2 yl-methylene hydrazine carbothioamide (Rx-6) and pyridine 2-yl-methylene hydrazine carboxamide (Rx-7) IC50 = 1.07 ± 0.043 µM, 2.18 ± 0.058 µM both possessed significant activity. Furthermore, molecular docking and kinetic studies were performed for the most potent inhibitors to demonstrate the binding mode of the active pyridine carbothioamide with the enzyme urease and its mode of interaction. The ADME profile also showed that all the synthesized molecules present oral bioavailability and high GI absorption.

The X-ray diffraction study of three compounds containing 2,3-dihydroxybenzaldehyde semicarbazone (H3L1) or 2-hydroxy-3-methoxybenzaldehyde semicarbazone (H2L2) shows the formation of one organic salt with protonated triethylamine [(C2H5)3NH][H2L1]·0.5(CH3)2CO (I) and two new coordination nickel(II) compounds with these two differently substituted semicarbazones of salicylaldehyde [Ni(H3L1)(H2L1)](NO3)·2.5MeOH·0.25H2O (II) and [Ni(H2L2)2]Cl2·4H2O (III) (CIF files CCDC nos. 2041894–2041896 (I–III)). The Ni(II) compounds are ionic and formed by the complex cations with the same metal to ligand ratio. The Ni(II) ion in these complex cations is characterized by a distorted octahedral coordination geometry formed by a set of donor atoms N2O4 of two ligands coordinated via the tridentate mode. In the monocharged complex cation of compound II, two coordinated ligands are not identical. One of them acts as the neutral chelating agent (H3L1), and the second ligand is deprotonated and involved as the monoanion (H2L1)–. Both H2L ligands are neutral in the complex cation of compound III. In the crystal, all the three compounds form supramolecular ensembles of diverse dimensionality and architecture, and their components are joined by weak interactions of different types. [ABSTRACT FROM AUTHOR]

The title compound, C17H17N3O, crystallizes with two independent molecules in the asymmetric unit. The semicarbazone moieties of these independent molecules (I and II) are essentially planar [maximum deviation of 0.042 (1) Å in molecule I and 0.041 (1) Å in molecule II], with the terminal phenyl rings twisted away from the mean plane of the semicarbazone moiety, making dihedral angles of 60.26 (8) and 28.76 (9)° in molecule I and 31.07 (9) and 35.45 (8)° in molecule II. The molecules both exhibit an E configuration with respect to the C=C and azomethine C=N bonds. In the crystal, two classical N—H...O hydrogen-bonding interactions are present between the two molecules, forming a centrosymmetric dimer, while a weak C—H...O non-classical hydrogen-bonding interaction, with a donor–acceptor distance of 3.476 (2) Å, interconnects two neighbouring centrosymmetric dimers to form a cage-like structure. These cage structures are interconnected by weak C—H...π interactions with an H...π distance of 2.790 Å, forming supramolecular chains along the c-axis direction.

In the title compound, C13H14N4O·2H2O, the organic molecule is almost planar. In the crystal, the molecules are linked by O—H...O, N—H...O and O—H...N hydrogen bonds, forming a two-dimensional network parallel to (10\overline{1}). Hirshfeld surface analysis and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H...H (55.4%), H...O/O...H (14.8%), H...C/C...H (11.7%) and H...N/N...H (8.3%) interactions.

The condensation product of isatin with semicarbazide(IstscabH), thiosemicarbazide (IsttscabH) and thiocarbohydrazide (BisttcabH) form inclusion complexes with β-cyclodextrin (β-cydx=C42H70O35), in 1:1 molar ratio having composition [β-cydx-IstscabH/IsttscabH] and [(β-cydx-BisttcabH)]. The inclusion complexes have been charactised from the studies of IR, UV, NMR and molecular weight determination. The inclusion products are thermally more stable than β-cyclodextrin (240°C). The IR, UV and NMR spectra of isatin derivatives are affected on forming inclusion complexes with β-cyclodextrin ring. The inclusion products as well as isatin derivatives show ionic nature at room temperature in DMF solution. The antibacterial activity of inclusion products are larger than simple Schiff bases. [ABSTRACT FROM AUTHOR]

The synthesis of new 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives from triterpenoid ketones has been investigated via the corresponding semicarbazones. The intermediates 5, 8 have also been isolated, separated and their structures identified. The Hurd–Mori reaction and Lalezari method have been applied to synthesize a series of new substances 6 and 7. The regioselectivity of the functionalization mostly was centered at the C-3 position for the products 9 and 10. The structures of these compounds were confirmed by 2D-NMR spectroscopy. [ABSTRACT FROM AUTHOR]

A series of novel functionalized p-tert-butyldihomooxacalix[4]arene mono-Schiff bases were conveniently synthesized by two-step reaction process. The synthetic rout included alkylation of p-tert-butyldihomooxacalix[4]arene with O-chloroalkoxy-substituted benzaldehydes and sequential condensation with 2-hydroxybenzohydrazide, 2-picolinohydrazideand aminothiourea. The single crystal structures of two p-tert-butyldihomooxacalix[4]arenederivatives were determined by X-ray single crystal diffraction method. The coordination abilities of dihomooxacalix[4]arene mono-Schiff bases towards transition metal ions were preliminarily investigated by UV-Vis spectra. [ABSTRACT FROM AUTHOR]

Two novel Cu(I) complexes with the 2-acetylpyridine-N(4)-phenyl semicarbazone (HL) ligand, [CuCl (HL)(PPh3)]∙CH3CN (1) and [CuBr (HL)(PPh3)] (2), were investigated by single-crystal X-ray analysis, Hirshfeld surface, and physicochemical and spectroscopic methods. In both cases, the Schiff base was coordinated by the bidentate ligand via the pyridine nitrogen and the iminic nitrogen atoms. A molecule of triphenylphosphine and a halide ion (Cl− or Br−) completed the coordination sphere of the metal centers. The geometry around the copper atoms was distorted tetrahedral geometry. The secondary coordination sphere of Cu(I) is pentacoordinated and has weak interactions Cu···O of 2.906(1) Å and 2.783(1) Å. The 3D Hirshfeld surface and the 2D fingerprint plots of the complexes were analyzed quantitatively to verify the presence of intermolecular interactions. By their crystal structure of (2), it is possible to observe π···π stacking interactions between the pyridyl and phenyl rings from HL and also between phenyl rings and the triphenylphosphine ligands forming a 1D network. The biological activity of the Cu(I) salts, the free semicarbazone, and its Cu(I) complexes was evaluated against human cancer cell lines MCF-7 and nontumor cell lines PBMC. [ABSTRACT FROM AUTHOR]

The studies on extraction of Co(II) and Cu(II) from aqueous solutions of waste material into the organic phase using 4-nitrobenzaldehydesemicarbazone were found to be sufficient. However, it was observed that the extraction increases when the pH of the solution was increased and extraction was found to be higher for Cu(II) in comparison with Co(II). This supports the following type of extraction mechanism. (Mn+)aq + m (HL) org = [MLn (m-n)HL]org + n(H+)aq. The extraction decreases with increased concentration of metal ion whereas the Sandell sensitivity and metal/ligand ratio were found to be 0.0049µgcm-2 and 1:2 respectively. The determination of Co(II) and Cu(II) has also been executed in the existence of foreign ions. [ABSTRACT FROM AUTHOR]

The present work reports the synthesis and structural elucidation of six novel copper(II) complexes with 2-acetylpyridine semicarbazone (HL1) and 2-acetylpyridine N(4)-phenyl semicarbazone (HL2). In all compounds, the semicarbazone ligands were find tridentate with NNO-donor atoms. The single crystal X-ray diffraction analysis showed the influences of the different copper salt starting reagent in the crystal structures. A packing architectures analysis has been undertaken to delineate the role of relevant noncovalent interactions. The π···π stacking interactions and hydrogen bonds were analyzed using the Hirshfeld surface and fingerprint plots. In addition, the compounds were also characterized by physicochemical and spectroscopic methods. A new ligand and six copper(II) complexes of semicarbazone derivatives have been synthesized and their crystal structures have been studied. Spectroscopy experiments and Hirshfeld Surface were analyzed. [ABSTRACT FROM AUTHOR]

• The review highlights the general methods of synthesizing semicarbazones, emphasizing their versatility and wide applicability in various research fields. • The review explores the extensive range of biological and biomedical applications of semicarbazones. • The review underscores the potential for future innovations and discoveries. Semicarbazones are a type of chemical compound which are formed by the condensation reaction of imines with aldehydes or ketones. These compounds are highly adaptable and flexible in their applications. Transition metal complexes containing imine ligands, such as Zn, Cu and Cd. have been proven to be effective predecessors for the production of metal or metal chalcogenide nanoparticles. In recent times, scientists have been closely studying semicarbazones and their metal complexes due to their potential use in various fields such as pharmacology, nanotechnology, and biological composite oxidation. These versatile compounds have shown promising results in areas such as antifungal, antiviral, antituberculosis, anticancer, antimalarial, anti-HIV, and catalytic applications. The researchers have also analyzed the spectroscopic data such as IR and NMR of these complexes. Mononuclear, binuclear and also polynuclear complexes of semicarbazones are also discussed. This review covers a variety of semicarbazone complexes grouped according to their characteristics. However, there is potential for the synthesis of new and unique semicarbazone complexes that could have significant activity in the fields of biology and pharmaceuticals. These future developments are expected to generate significant interest. The synthetic root of some of these derivatives and complexes is evaluated as for biological activities in line with this biological potential in order to arrange the various biological activities of certain synthesized semicarbazone derivatives with transition metals. [Display omitted] [ABSTRACT FROM AUTHOR]

Two new series of betulin derivatives with semicarbazone (7a–g) or thiosemicarbazone (8a–g) groups at the C-28 position were synthesized. All compounds were evaluated for their in vitro cytotoxicities in human hepatocellular carcinoma cells (HepG2), human breast carcinoma cells (MCF-7), human lung carcinoma cells (A549), human colorectal cells (HCT-116) and normal human gastric epithelial cells (GES-1). Among these compounds, 8f displayed the most potent cytotoxicity with an IC50 value of 5.86 ± 0.61 μM against MCF-7 cells. Furthermore, the preliminary mechanism studies in MCF-7 cells showed that compound 8f could trigger the intracellular mitochondrial-mediated apoptosis pathway by losing MMP level, which was related with the upregulation of Bax, P53 and cytochrome c expression; the downregulation of Bcl-2 expression; activation of the expression levels of caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9; and an increase in the amounts of intracellular reactive oxygen species. These results indicated that compound 8f may be used as a valuable skeleton structure for developing novel antitumor agents.

Polypeptide materials offer scalability, biocompatibility, and biodegradability, rendering them an ideal platform for biomedical applications. However, the preparation of polypeptides with specific functional groups, such as semicarbazide moieties, remains challenging. This work reports, for the first time, the straightforward synthesis of well-defined methoxy-terminated poly(ethylene glycol)-b-polypeptide hybrid block copolymers (HBCPs) containing semicarbazide moieties. This synthesis involves implementing the direct polymerization of environment-stable N-phenoxycarbonyl-functionalized α-amino acid (NPCA) precursors, thereby avoiding the handling of labile N-carboxyanhydride (NCA) monomers. The resulting HBCPs containing semicarbazide moieties enable facile functionalization with aldehyde/ketone derivatives, forming pH-cleavable semicarbazone linkages for tailored drug release. Particularly, the intracellular pH-triggered hydrolysis of semicarbazone moieties restores the initial semicarbazide residues, facilitating endo-lysosomal escape and thus improving therapeutic outcomes. Furthermore, the integration of the hypoxic probe (Ir(btpna)(bpy) 2 ) into the pH-responsive nanomedicines allows sequential responses to acidic and hypoxic tumor microenvironments, enabling precise detection of metastatic tumors. The innovative approach for designing bespoke functional polypeptides holds promise for advanced drug delivery and precision therapeutics., (© 2023 Wiley-VCH GmbH.)

Aim: A series of semicarbazone and thiosemicarbazone-tailed hybrids comprising pyrazole and acetylisoxazoline were prepared from (R)-carvone and characterized by technique spectroscopies Nuclear Magnetic Resonance (NMR), IR and High-Resolution Mass Spectrometry. Density Functional Theory (DFT) determined the structural parameters. Their cytotoxic activity was evaluated in vitro against four human cancer cell lines. Methods & results: All the studied semi and thiosemicarbazone demonstrate a promising potential as anticancer agents. The mechanism of action of these compounds involves apoptosis in HT-1080 cells, supported by an increase in the level of caspase-3/7 activity, which also arrests the cell cycle in the G0/G1 phase. Molecular docking studies were performed to establish the potential of the most active compounds 4a and 5a . ADMET analysis showed appropriate pharmacokinetic properties, allowing structure prediction for anticancer activity.

Novel spiro(3-hydroxy-5,5-dimethyl)-1,5'-(2'-substituated[1,3,4]-oxadiazole/thiadiazolo[3,2-c] thiazolines and 3-hydroxy-5,5-dimethyl-spiro[cyclohex-2-ene-thiazolo/thiazino[3,2-b]-s-tetrazine were prepared from previously reported hydrazone, semicarbazone, carbazone, and spiro-s-tetrazine intermediates derived from dimedone precursor. All the newly synthesized heterocycles have been characterized by analytical and spectral (1H NMR and hC NMR) data and screened their in vitro antibacterial activity against gram negative bacteria Escherichia coli and gram positive bacteria Staphylococcus aureus. Some of the compounds showed moderate to good activities towards the bacteria chosen. [ABSTRACT FROM AUTHOR]

Four Cu(II) complexes [CuLH2O](ClO4)2, 1; [CuLCl]Cl.H2O, 2; [CuLBr]2(Cu3Br5), 3; and [CuLH2O](NO3)2, 4; where L = tetradentate semicarbazone ligand, have been synthesized and characterized by elemental analysis, FT-IR and UV–Vis. The structures of compounds 1 and 3 have been determined by single-crystal X-ray diffraction analyses. In mononuclear 1, the semicarbazone, L acts as a tetradentate neutral ligand and a water molecule also coordinates to the Cu atom. There are two independent [CuL(H2O)]2+ cations and four perchlorate anions in the crystallographic asymmetric unit. One of the cations has a weak interaction between its Cu atom and a O atom of an adjacent perchlorate anion. The structure of 3 contains two independent [CuLBr]+ cations and a (Cu3Br5)2− anion. The coordination geometry around the cation's Cu(II) ion is five-coordinated square pyramidal, with L acting as a tetradentate neutral ligand and with a Br at the apical position. The Cu3Br52− anions link to one another to form an infinite one-dimensional (Cu3Br52−)n chain. Furthermore, the Hirshfeld surface analyses and the 2D fingerprint plot have been discussed. [ABSTRACT FROM AUTHOR]

Gold‐catalyzed functionalization of semicarbazides (ArNHCONHNH2) with various terminal alkynes R2C≡CH (R2 = Alk or Ar) in the presence of Ph3PAuNTf2 (3 mol‐%) grants a range of substituted semicarbazones (16 examples; 64–93 %). This novel metal‐catalyzed coupling proceeds under mild conditions (PhCl, 60 °C) and demonstrates a high functional group tolerance; the reaction is sensitive to the electronic effects of the substituents in terminal alkynes. Inspection of XRD solid‐state structures of three obtained semicarbazones proved their dimerization via weak to moderate strength hydrogen bonding. The structures of the semicarbazones in solutions were studied by concentration dependent 1H NMR and 2D NMR and these experiments proved the presence of H‐bonds between two molecules. The nature and energy of H‐bonding (3.8–5.1 kcal/mol), degree of electron density delocalization, and rotational barriers via various bonds in the equilibrium model structures were studied by DFT calculations at the M06‐2X/6‐311++G** level of theory. [ABSTRACT FROM AUTHOR]

Background: Various substituted semicarbazones and oxadiazols have been widely investigated for their insecticidal and pharmacological activities. Heterocyclic analogs of these types were extensively studied for their biological activities. In this study insecticidal activity of semicarbazones and oxadiaziole created our interest to prepare and screen the activity. Objectives: To prepare a series of substituted semicarbazones and oxadiazoles, with an observation to subjecting them for insecticidal and pharmacological screening. Methodology: An oxalic acid dicarbohydrazide compound was prepared by a mixture of diethyl oxalate (0.1 mole), hydrazine hydrate (99%) (0.2 mole) and 2-3 drops of Conc. HCl in absolute ethanol. Resulted compound was reflexed with different substituted aldehyde (0.05 moles) with addition of 1-2 drops of Conc. HCl in an absolute ethanol to acquired bis-semicarbazones. Derived bis-semicarbazones were subjected for oxidation using ferrichloride (20mg) and acetic acid (8mL) to obtain oxadiazole derivatives. Results: The compounds 2c-d and 3a showed high percentage of mortality in an insecticidal activity. Compounds 3a and 3b exhibited high anti-bacterial activity against Kallipsi calla, in case of Escherichia coli the compound 2d, 3a, 3c and 3d shows maximum activity. Compounds 3a and 3d showed high anti-fungal activity against A. nigar and 3c against A. flavous. The compounds 2a, 2b, 3c have shown good anti-inflammatory activity. Compound 3d showed a competitive inhibitory activity and act as lead molecule towards the drug designing. Conclusion: The present study exposed that the synthesized compounds exhibit significant insecticidal, anti-bacterial, anti-fungal, anti-inflammatory activity and act as lead molecule towards the drug designing. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the in vitro and in vivo leishmanicidal activity of synthetic compounds, containing a semicarbazone scaffold as a peptide mimetic framework. The leishmanicidal effect against amastigotes of Leishmania amazonensis was also evaluated at concentration of 100 μM–0.01 nM. The derivatives 2e, 2f, 2g and 1g, beyond the standards miltefosine and pentamidine, significantly diminished the number of L. amazonensis amastigotes in macrophages. These derivatives were also active against amastigotes of L. braziliensis. As 2g presented potent leishmanicidal activity against the amastigotes of L. amazonensis in macrophages, we also investigated the in vivo leishmanicidal activity of this compound against L. amazonensis. Approximately 105 L. amazonensis promastigotes were subcutaneously inoculated into the dermis of the right ear of BALB/c mice, which were subsequently treated with 2g (p.o. or i.p.), miltefosine (p.o.) or glucantime (i.p.) at 30 μmol/kg/day x 28 days. Thus, a similar reduction in the lesion size was observed after the administration of 2g through oral (63.7 ± 10.1%) and intraperitoneal (61.8 ± 3.7%) routes. A larger effect was observed after treatment with miltefosine (97.7 ± 0.4%), and glucantime did not exhibit activity at the dose administered. With respect to the ear parasite load, 2g diminished the number of parasites by p.o. (30.5 ± 5.1%) and i.p. (33.3 ± 4.3%) administration. In addition, 2g induced in vitro apoptosis, autophagy and cell cycle alterations on L. amazonensis promastigotes. In summary, the derivative 2g might represent a lead candidate for antileishmanial drugs, as this compound displayed pronounced leishmanicidal activity. Image 1 • Semicarbazone were evaluated in vitro against L. amazonensis and L.braziliensis. • L. amazonensis and L.braziliensis were susceptible to 2g (LASSBIO-1483). • 2g induced in vitro apoptosis, autophagy and cell cycle arrest on L. amazonensis. • 2g presented leishmanicidal activity against L. amazonensis. [ABSTRACT FROM AUTHOR]

Abstract Two novel semicarbazone-lanthanide(III) complexes were prepared and structurally characterized as [Ln (Hscpy) 2 (NO 3) 2 ]NO 3 ·MeOH (Ln = Gd and Tb; Hscpy = 1-((E)-2-pyridinylmethylidene)semicarbazone). The 4f metal ions experience deca-coordination geometry. Each molecular formula contains two neutral Hscpy molecules in the keto form coordinated through two nitrogen atoms and one oxygen atom, while two nitrate ligands are both coordinated in a chelate mode. The 1 + charge of the cation-complex is balanced by a nitrate anion. Extensive intermolecular hydrogen bonds are formed through the methanol solvate molecule, which acts both as a donor and an acceptor molecule. The chemical composition of the compounds was confirmed by high resolution mass spectra (ESI-MS); peaks at m/z = 122.07 and 148.05, assigned to the fragments C 6 H 8 N 3 + and C 7 H 6 N 3 O+, respectively, are in agreement with the coordination of Hscpy. Alternating current magnetic susceptibility analysis was performed in the 10–10000 Hz range, and the terbium-complex showed slow relaxation of the magnetization when immersed in a static magnetic field of 1 kOe and 1.5 kOe, with an activation barrier to the relaxation (21.9(4) cm−1) among the highest found for ten-coordinated Tb(III) complexes. This behavior of slow relaxation of the magnetization is relevant as a memory effect regarding the development of Single Molecule Magnets (SMM). Graphical abstract Synthesis, structural and magnetic characterization of two lanthanide complexes containing 2-formylpyridine semicarbazone (HSCpy) is discussed. Image 1 Highlights • Structural and Magnetic investigation of semicarbazone Gd(III) and Tb(III) complexes. • Asymmetric and supramolecular 3D assembly in the solid state. • Terbium complex shows a high activation barrier to relaxation. [ABSTRACT FROM AUTHOR]

The title compound, C17H17N3O, crystallizes with two independent molecules in the asymmetric unit. The semicarbazone moieties of these independent molecules (I and II) are essentially planar [maximum deviation of 0.042 (1) Å in molecule I and 0.041 (1) Å in molecule II], with the terminal phenyl rings twisted away from the mean plane of the semicarbazone moiety, making dihedral angles of 60.26 (8) and 28.76 (9)° in molecule I and 31.07 (9) and 35.45 (8)° in molecule II. The molecules both exhibit an E configuration with respect to the C＝C and azomethine C＝N bonds. In the crystal, two classical N--H...O hydrogen-bonding interactions are present between the two molecules, forming a centrosymmetric dimer, while a weak C--H...O nonclassical hydrogen-bonding interaction, with a donor-acceptor distance of 3.476 (2) Å, interconnects two neighbouring centrosymmetric dimers to form a cage-like structure. These cage structures are interconnected by weak C--H...π interactions with an H...π distance of 2.790 Å, forming supramolecular chains along the c-axis direction. [ABSTRACT FROM AUTHOR]

Abstract: A new series of semicarbazone-triazole hybrid derivatives have been synthesized by condensation between heterocyclic aldehydes and the commercial semicarbazide hydrochloride. The in vitro antioxidant activity of these species was tested using 1,1-diphenyl-2-picrylhydrazyl radical, 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) and Ferric reducing antioxidant power assays and their antimicrobial activity against different microbial strains was carried out. Furthermore, molecular properties prediction and drug likeness were also determinated using Molinspiration. Among such derivatives, compounds (E)-2-(4-((1-(2,6-dimethylphenyl)-1H-1,2,3-triazol-4-yl)methoxy)benzylidene)hydrazine carboxamide (4c), and (E)-2-(4-((1-(2-methoxyphenyl)-1-H-1,2,3-triazol-4-yl)methoxy)benzylidene)hydrazine-carboxamide (4e) exhibit excellent scavenging ability, especially with IC50 = 1.57 ± 1.66 mg/mL (4c) and IC50 = 1.82 ± 0.15 mg/mL (4e) with 1,1-diphenyl-2-picrylhydrazyl radical and IC50 = 1.90 ± 1.33 mg/mL (4c) with 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) as compared to the standards butylhydroxytoluene (IC50 = 1.60 ± 1.98 mg/mL) and Trolox (IC50 = 1.45 ± 1.33 mg/mL), respectively. The antimicrobial assay results, show that compounds 4c and 4e highlighted the most interesting profile with the potent activity was obtained against S. enteritidis (1.56-fold) and then M. luteus (1.45-fold) which are significantly higher than the positive control, chloramphenicol. By the other hand, the synthesized semicarbazone derivatives met the Lipinski's rule criteria by presenting good drug likeness and bioactivity scores. The structure-property-activity relationships have been carried out in order to determine the effect of various substituents on the molecular and the biological properties. All these investigations confirm that our synthetic semicarbazone can be explored for generating new potential drug with good oral bioavailability.Graphical abstract: [ABSTRACT FROM AUTHOR]

Abstract Thiazole, thiosemicarbazone and semicarbazone moieties are privileged scaffolds (acting as primary pharmacophores) in many compounds that are useful to treat several diseases, mainly tropical infectious diseases. In this review article, we critically analyzed the contribution of these scaffolds to medicinal chemistry in the last five years, focusing on tropical infectious diseases, such as Chagas disease, human African trypanosomiasis (HAT), leishmaniasis, and malaria. We also present perspectives for their use in drug design in order to contribute to the development of new drugs. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Nanosized titania has promising application in the field of photocatalysis, optical coating and solar cell. Metal alkoxides based sol-gel methodology is one of the established & extensively used route for the preparation of nano-titania. In present work, nanosized titania have been prepared through sol-gel transformation of synthesised and chemically modified metal complex using titanium(IV) isopropoxide (TTIP). Modifications of metal alkoxides with chelating ligands result in the controlled condensation of TTIP. Metal complexes of TTIP were chemically modified by various schiffs bases. Phase of nano-sized titania was confirmed by X-ray diffraction and Fourier transform infrared spectroscopy. Shape, size and surface morphology were examined using scanning electron microscopy and high-resolution transmission electron micsroscopy. Elemental composition was investigated by energy disperse X-ray analysis. The absorption spectra and thus optical band gap were determined using Ultraviolet and visible spectroscopy. [ABSTRACT FROM AUTHOR]

A series of semicarbazones, thiosemicarbazones, 1,3,4-oxadiazoles/thiadiazoles bearing pyrazole scaffold were designed and synthesized. All the synthesized new compounds were characterized by 1H NMR, 13C NMR, MS and elemental analysis. The synthesized compounds were screened to probe their in vitro antimicrobial activity against bacteria and fungi species. The structure-activity relationship of the synthesized compounds was studied. The compounds displayed good to excellent potency against tested microorganisms. The in vitro antioxidant activities of the 1,3,4-oxadiazoles/thiadiazoles were evaluated by DPPH, hydroxyl and nitric oxide radical scavenging assay. Among the tested compounds, compound with chloro substitution showed good antioxidant potential.

Thermodynamic and kinetic mechanisms of forming six semicarbazones have been investigated computationally by DFT B3LYP method. All the reactions proceed via two transitions and include two consecutive steps: bimolecular and unimolecular. The computed transition steps have varying equilibrium constants values, enthalpy of activation and Gibbs energy of activation, depending on the semicarbazone involved.

A series of novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone (7a−g) or thiosemicarbazone (7h−k) side chain were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, HCT-116, MCF-7, and A549) using the MTT assay in vitro. The results showed that compound 7j exhibited significant cytotoxic activity against HepG2 cells (IC50 = 3.52 μM), being more potent than ergosterol peroxide. Further cellular mechanism studies in HepG2 cells indicated that compound 7j triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential (MMP), which was associated with up-regulation of Bax, down-regulation of Bcl-2, activation levels of the caspase cascade, and formation of reactive oxygen species (ROS). The above findings indicated that compound 7j may be used as a promising skeleton for antitumor agents with improved efficacy.

The four compounds, namely: 5-nitro-2-furaldehyde thiosemicarbazone (1); 5-nitro-2-thiophene thiosemicarbazone (2); 5-nitro-2-furaldehyde semicarbazone (3); and 5-nitro-2-thiophene semicarbazone (4) were synthesized and crystallized. The three new crystal structures of 1, 2, and 4 were determined and compared to three already known crystal structures of 3. Additionally, two new polymorphic forms of 1 solvate were synthesized and studied. The influence of the exchange of 2-thiophene to 2-furaldehyde as well as thiosemicarbazone and semicarbazone on the self-assembly of supramolecular nets was elucidated and discussed in terms of the formed synthons and assemblies accompanied by Full Interaction Maps analysis. Changes in the strength of IR oscillators caused by the molecular and crystal packing effects are described and explained in terms of changes of electron density.