Six organotin(IV) complexes, viz., [Me2Sn(L)] (1), [n-Bu2Sn(L)] (2), [n-Oct2Sn(L)] (3), [Bz2Sn(L)]·0.5C7H8 (4), [n-BuSn(L)Cl] (5), and [PhSn(L)Cl] (6), were synthesized using a 2,6-diacetylpyridine bis(2-hydroxybenzoylhydrazone), H2L. Compounds were characterized by Fourier transform infrared (FT-IR), High-resolution mass spectrometry (HRMS), and solutions Fourier transform nuclear magnetic resonance (FT-NMR) spectroscopies. The structures 1-6 were established by single-crystal X-ray diffraction (SC-XRD) analysis. Diffraction results evidenced that complexes 1-6 were seven-coordinated mononuclear species with the equatorial plane comprising the pentagonal N3O2 chelate ring of the doubly deprotonated L and two axial ligands, either R (R = Me, n-Bu, n-Oct, Bz) or R (n-Bu or Ph) and Cl ligands. Additionally, the photophysical properties were examined due to the enhanced conjugation and rigidity of the molecules while thermogravimetric analysis was carried out to evaluate the thermal stabilities of compounds. The anti-proliferative activity of the complexes 1-6 was tested against prostate cancer cells (DU-145) and normal human embryonic kidney cells (HEK-293). Among the compounds, dibutyltin compound 2 exhibited increased anti-proliferative activity, with an IC50 value of 6.16 ± 1.56 μM. The investigation of its mechanism of action involves using AO/EB (acridine orange/ethidium bromide) and ROS (reactive oxygen species) generation assays. This likely detects apoptotic morphological alterations in the nucleus of the cells, with ROS generation ultimately leading to apoptosis and cell death. The superior activity of 2 may be attributed to the C···H contacts and respective higher de outside and di inside distances from the Hirshfeld surface. Thus, these compounds could be a promising alternative to classical chemotherapy agents.

• Klíčová slova
• Crystal structure, Cytotoxicity, Heptacoordinate complexes, N(3)O(2)-pentadentate ligand, Organotin, Spectroscopy,
• MeSH
• antitumorózní látky * farmakologie   chemická syntéza   chemie   MeSH
• hydrazony chemie   farmakologie   chemická syntéza   MeSH
• komplexní sloučeniny farmakologie   chemická syntéza   chemie   MeSH
• krystalografie rentgenová MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• organocínové sloučeniny * chemie   farmakologie   chemická syntéza   MeSH
• proliferace buněk * účinky léků   MeSH
• pyridiny chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky * MeSH
• hydrazony MeSH
• komplexní sloučeniny MeSH
• organocínové sloučeniny * MeSH
• pyridiny MeSH

Inhibition of the human O-linked β-N-acetylglucosaminidase (hOGA, GH84) enzyme is pharmacologically relevant in several diseases such as neurodegenerative and cardiovascular disorders, type 2 diabetes, and cancer. Human lysosomal hexosaminidases (hHexA and hHexB, GH20) are mechanistically related enzymes; therefore, selective inhibition of these enzymes is crucial in terms of potential applications. In order to extend the structure-activity relationships of OGA inhibitors, a series of 2-acetamido-2-deoxy-d-glucono-1,5-lactone sulfonylhydrazones was prepared from d-glucosamine. The synthetic sequence involved condensation of N-acetyl-3,4,6-tri-O-acetyl-d-glucosamine with arenesulfonylhydrazines, followed by MnO2 oxidation to the corresponding glucono-1,5-lactone sulfonylhydrazones. Removal of the O-acetyl protecting groups by NH3/MeOH furnished the test compounds. Evaluation of these compounds by enzyme kinetic methods against hOGA and hHexB revealed potent nanomolar competitive inhibition of both enzymes, with no significant selectivity towards either. The most efficient inhibitor of hOGA was 2-acetamido-2-deoxy-d-glucono-1,5-lactone 1-naphthalenesulfonylhydrazone (5f, Ki = 27 nM). This compound had a Ki of 6.8 nM towards hHexB. To assess the binding mode of these inhibitors to hOGA, computational studies (Prime protein-ligand refinement and QM/MM optimizations) were performed, which suggested the binding preference of the glucono-1,5-lactone sulfonylhydrazones in an s-cis conformation for all test compounds.

• Klíčová slova
• Prime refinement, QM/MM optimization, glyconolactone sulfonylhydrazone, hHexB, hOGA, inhibitor,
• MeSH
• antigeny nádorové chemie   metabolismus   MeSH
• beta-hexosaminidasa, beta řetězec chemie   metabolismus   MeSH
• histonacetyltransferasy chemie   metabolismus   MeSH
• hyaluronoglukosaminidasa chemie   metabolismus   MeSH
• hydrazony chemická syntéza   chemie   farmakologie   MeSH
• inhibitory enzymů chemická syntéza   chemie   farmakologie   MeSH
• laktony chemie   MeSH
• lidé MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• oxidy chemie   MeSH
• sloučeniny manganu chemie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové MeSH
• beta-hexosaminidasa, beta řetězec MeSH
• HEXB protein, human MeSH Prohlížeč
• histonacetyltransferasy MeSH
• hyaluronoglukosaminidasa MeSH
• hydrazony MeSH
• inhibitory enzymů MeSH
• laktony MeSH
• manganese dioxide MeSH Prohlížeč
• OGA protein, human MeSH Prohlížeč
• oxidy MeSH
• sloučeniny manganu MeSH

Hydrazones and their derivatives are very important compounds in medicinal chemistry due to their reported biological activity for the treatment of several diseases, like Alzheimer's, cancer, inflammation, and leishmaniasis. However, most of the investigations on hydrazones available in literature today are directed to the synthesis of these molecules with little discussion available on their biological activities. With the purpose of bringing lights into this issue, we performed a revision of the literature and wrote this review based on some of the most current research reports of hydrazones and derivatives, making it clear that the synthesis of these molecules can lead to new drug prototypes. Our goal is to encourage more studies focused on the synthesis and evaluation of new hydrazones, as a contribution to the development of potential new drugs for the treatment of various diseases.

• Klíčová slova
• Alzheimer's, Hydrazones, biologic activity, cancer, guanylhydrazones, leishmaniasis, medicinal chemistry.,
• MeSH
• hydrazony chemická syntéza   farmakologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• hydrazony MeSH

BACKGROUND: Hydrazide-hydrazones have been known as scaffold with various biological activities including inhibition of acetyl- (AChE) and butyrylcholinesterase (BuChE). Cholinesterase inhibitors are mainstays of dementias' treatment. OBJECTIVE: Twenty-five iodinated hydrazide-hydrazones and their analogues were designed as potential central AChE and BuChE inhibitors. METHODS: Hydrazide-hydrazones were synthesized from 4-substituted benzohydrazides and 2-/4- hydroxy-3,5-diiodobenzaldehydes. The compounds were investigated in vitro for their potency to inhibit AChE from electric eel and BuChE from equine serum using Ellman's method. We calculated also physicochemical and structural parameters for CNS delivery. RESULTS: The derivatives exhibited a moderate dual inhibition with IC50 values ranging from 15.1-140.5 and 35.5 to 170.5 μmol.L-1 for AChE and BuChE, respectively. Generally, the compounds produced a balanced or more potent inhibition of AChE. N'-[(E)-(4-Hydroxy-3,5-diiodophenyl)methylidene]-4- nitrobenzohydrazide 2k and 4-fluoro-N'-(2-hydroxy-3,5-diiodobenzyl)benzohydrazide 3a were the most potent inhibitors of AChE and BuChE, respectively. Structure-activity relationships were established, and molecular docking studies confirmed interaction with enzymes. CONCLUSION: Many novel hydrazide-hydrazones showed lower IC50 values than rivastigmine against AChE and some of them were comparable for BuChE to this drug used for the treatment of dementia. They interact with cholinesterases via non-covalent binding into the active site. Based on the BOILEDEgg approach, the majority of the derivatives met the criteria for blood-brain-barrier permeability.

• Klíčová slova
• 1, 2-diacylhydrazine, Acetylcholinesterase, Butyrylcholinesterase, Enzyme inhibition, Hydrazides, Hydrazones,
• MeSH
• acetylcholinesterasa metabolismus   MeSH
• butyrylcholinesterasa metabolismus   MeSH
• cholinesterasové inhibitory chemická syntéza   chemie   farmakologie   MeSH
• Electrophorus MeSH
• hydraziny chemická syntéza   chemie   farmakologie   MeSH
• hydrazony chemická syntéza   chemie   farmakologie   MeSH
• koně MeSH
• molekulární struktura MeSH
• simulace molekulového dockingu MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• butyrylcholinesterasa MeSH
• cholinesterasové inhibitory MeSH
• hydraziny MeSH
• hydrazony MeSH

The effect of hydrazide linkers on the formation and mechanical properties of hyaluronan hydrogels was intensively evaluated. The reaction kinetics of hydrazone formation was monitored by NMR spectroscopy under physiological conditions where polyaldehyde hyaluronan (unsaturated: ΔHA-CHO, saturated: HA-CHO) was reacted with various hydrazides to form hydrogels. Linear (adipic, oxalic dihydrazide) and branched (N,N´,N´´-tris(hexanoylhydrazide-6-yl)phosphoric triamide and 4-arm-PEG hydrazide) hydrazides were compared as crosslinking agents. The mechanical properties of hydrogels were also modified by attaching a hydrophobic chain to HA-CHO; however, it was found that this modification did not lead to an increase in hydrogel stiffness. Cytotoxicity tests showed that all tested hydrazide crosslinkers reduced the viability of cells only slightly, and that the final hyaluronan hydrogels were non-toxic materials.

• Klíčová slova
• Schiff base, acylation, hyaluronan, hydrazone, hydrogel,
• MeSH
• acylace MeSH
• biokompatibilní materiály chemická syntéza   chemie   toxicita   MeSH
• buňky Swiss 3T3 MeSH
• hydraziny chemická syntéza   chemie   toxicita   MeSH
• hydrazony chemická syntéza   chemie   toxicita   MeSH
• hydrogely chemická syntéza   chemie   toxicita   MeSH
• kinetika MeSH
• koncentrace vodíkových iontů MeSH
• kyselina hyaluronová analogy a deriváty   chemická syntéza   toxicita   MeSH
• modul pružnosti MeSH
• myši MeSH
• reagencia zkříženě vázaná chemická syntéza   chemie   toxicita   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• hydraziny MeSH
• hydrazony MeSH
• hydrogely MeSH
• kyselina hyaluronová MeSH
• reagencia zkříženě vázaná MeSH

Ten-eleven translocation protein (TET) 1 plays a key role in control of DNA demethylation and thereby of gene expression. Dysregulation of these processes leads to serious pathological states such as oncological and neurodegenerative ones and thus TET 1 targeting is highly requested. Therefore, in this work, we examined the ability of hydrazones (acyl-, aroyl- and heterocyclic hydrazones) to inhibit the TET 1 protein and its mechanism of action. Inhibitory activity of hydrazones 1-7 towards TET 1 was measured. The results showed a high affinity of the tested chelators for iron(II). The study clearly showed a significant correlation between the chelator's affinity for iron(II) ions (represented by the binding constant) and TET 1 protein inhibitory activity (represented by IC50 values).

• Klíčová slova
• Epigenetic, Hydrazone, Inhibitor, Iron(II) affinity, TET 1 protein,
• MeSH
• chelátory železa chemická syntéza   chemie   toxicita   MeSH
• dioxygenasy antagonisté a inhibitory   chemie   MeSH
• enzymatické testy MeSH
• epigeneze genetická účinky léků   MeSH
• hydrazony chemická syntéza   chemie   toxicita   MeSH
• inhibitory enzymů chemická syntéza   chemie   toxicita   MeSH
• železo chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chelátory železa MeSH
• dioxygenasy MeSH
• hydrazony MeSH
• inhibitory enzymů MeSH
• železo MeSH

Aroylhydrazone iron chelators such as salicylaldehyde isonicotinoyl hydrazone (SIH) protect various cells against oxidative injury and display antineoplastic activities. Previous studies have shown that a nitro-substituted hydrazone, namely, NHAPI, displayed markedly improved plasma stability, selective antitumor activity, and moderate antioxidant properties. In this study, we prepared four series of novel NHAPI derivatives and explored their iron chelation activities, anti- or pro-oxidant effects, protection against model oxidative injury in the H9c2 cell line derived from rat embryonic cardiac myoblasts, cytotoxicities to the corresponding noncancerous H9c2 cells, and antiproliferative activities against the MCF-7 human breast adenocarcinoma and HL-60 human promyelocytic leukemia cell lines. Nitro substitution had both negative and positive effects on the examined properties, and we identified new structure-activity relationships. Naphthyl and biphenyl derivatives showed selective antiproliferative action, particularly in the breast adenocarcinoma MCF-7 cell line, where they exceeded the selectivity of the parent compound NHAPI. Of particular interest is a compound prepared from 2-hydroxy-5-methyl-3-nitroacetophenone and biphenyl-4-carbohydrazide, which protected cardiomyoblasts against oxidative injury at 1.8 ± 1.2 μM with 24-fold higher selectivity than SIH. These compounds will serve as leads for further structural optimization and mechanistic studies.

• MeSH
• antioxidancia chemická syntéza   chemie   farmakologie   toxicita   MeSH
• antitumorózní látky chemická syntéza   chemie   farmakologie   toxicita   MeSH
• chelátory železa chemická syntéza   chemie   farmakologie   toxicita   MeSH
• hydrazony chemická syntéza   chemie   farmakologie   toxicita   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• oxidační stres účinky léků   MeSH
• radioizotopy železa MeSH
• stabilita léku MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia MeSH
• antitumorózní látky MeSH
• chelátory železa MeSH
• hydrazony MeSH
• Iron-59 MeSH Prohlížeč
• radioizotopy železa MeSH

We report the design and synthesis of novel anticancer agents based on bis-hydrazones separated by a rigid Tröger's base skeleton. This novel approach combines a biologically active moiety (hydrazone) with this scaffold (Tröger's base) to construct DNA intercalators. Evaluation of the anticancer activity of these agents using seven cancer cell lines and two healthy cell lines found that several derivatives had potent anticancer activity and excellent selectivity indexes toward cancer cells. The antimicrobial activities were tested on a set of thirteen bacterial stains, but the prepared compounds were not active. Complexation studies using biologically important metal ions demonstrated that these compounds are able to bind Cu(2+), Fe(3+), Co(2+), Ni(2+) and Zn(2+). DNA intercalation studies showed that the compounds themselves do not interact with DNA, but their metallocomplexes do interact, most likely via intercalation into DNA.

• Klíčová slova
• Anticancer agents, Cancer treatment, Complexation studies, Hydrazone, Tröger’s base,
• MeSH
• antitumorózní látky chemická syntéza   farmakologie   MeSH
• apoptóza účinky léků   fyziologie   MeSH
• buňky K562 MeSH
• HCT116 buňky MeSH
• hydrazony chemická syntéza   farmakologie   MeSH
• lidé MeSH
• preklinické hodnocení léčiv metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky MeSH
• hydrazony MeSH

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing the anticancer drug doxorubicin bound either by a proteolytically degradable bond (non-targeted PK1 or targeted with alpha-CD71 mAb) or by a hydrolytically degradable bond were synthesised and tested in vivo for various biological properties. Mouse 38C13 B-cell lympoma was used as a well established and defined cell line for this study. 38C13 cells are sensitive to free doxorubicin and IC50 was very low, about 0.014 microM. PK1 showed a strongly decreased cytostatic effect, IC50 being 12.6 microM. alpha-CD71 targeted conjugate, which can be considered as an antibody-targeted form of PK1, had IC50 0.358 microM. HPMA copolymer with doxorubicin bound via a hydrolytically sensitive bond (HYD conjugate) showed a high cytostatic effect with IC50 about 0.052 microM. We demonstrated that HYD conjugate inhibited DNA synthesis and induced p21(Waf1/Cip1) protein expression (p21(Waf1/Cip1) is cyclin-dependent kinase inhibitor which blocks cell cycle progression) as quickly as free doxorubicin, whereas PK1 acted much more slowly. Similarly, apoptosis induction measured by Annexin V binding and Caspase 3 activity was detected later after incubation of cells with PK1 or alpha-CD71 targeted conjugate. Apoptosis was manifested by elevation of bax and bad mRNA levels, which was much more rapid and intense in the case of free doxorubicin and HYD conjugate. Expression of antiapoptotic genes as well as cyclin-dependent kinases was surprisingly not affected.

• MeSH
• akrylamidy chemická syntéza   metabolismus   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• buněčná membrána účinky léků   patologie   MeSH
• buněčný cyklus genetika   MeSH
• DNA antagonisté a inhibitory   genetika   metabolismus   MeSH
• doxorubicin chemická syntéza   metabolismus   farmakologie   MeSH
• exprese genu účinky léků   genetika   MeSH
• geny myc účinky léků   genetika   MeSH
• hydrazony chemická syntéza   metabolismus   farmakologie   MeSH
• hydrolýza MeSH
• inhibiční koncentrace 50 MeSH
• inhibitor p21 cyklin-dependentní kinasy MeSH
• kaspasa 3 MeSH
• kaspasy škodlivé účinky   účinky léků   metabolismus   MeSH
• ligandy * MeSH
• messenger RNA genetika   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• preklinické hodnocení léčiv metody   MeSH
• proliferace buněk účinky léků   MeSH
• protein Bad MeSH
• protein X asociovaný s bcl-2 MeSH
• proteiny buněčného cyklu genetika   metabolismus   MeSH
• protoonkogenní proteiny c-bcl-2 genetika   metabolismus   MeSH
• receptory transferinu účinky léků   genetika   MeSH
• thymidin metabolismus   MeSH
• transportní proteiny genetika   metabolismus   MeSH
• tritium MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• akrylamidy MeSH
• Bad protein, mouse MeSH Prohlížeč
• Bax protein, mouse MeSH Prohlížeč
• Casp3 protein, mouse MeSH Prohlížeč
• Cdkn1a protein, mouse MeSH Prohlížeč
• DNA MeSH
• doxorubicin MeSH
• hydrazony MeSH
• inhibitor p21 cyklin-dependentní kinasy MeSH
• kaspasa 3 MeSH
• kaspasy MeSH
• ligandy * MeSH
• messenger RNA MeSH
• N-(2-hydroxypropyl)methacrylamide co-polymer-doxorubicin conjugate MeSH Prohlížeč
• protein Bad MeSH
• protein X asociovaný s bcl-2 MeSH
• proteiny buněčného cyklu MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• receptory transferinu MeSH
• thymidin MeSH
• transportní proteiny MeSH
• tritium MeSH

Antitrichomonal activity of selected 2,4-dinitro-phenylhydrazones and phenylosazones of sugars was investigated in vitro and in vivo and compared with the activity of tinidazole, an effective therapeutic agent. In experimental infections with Trichomonas vaginalis and Tritrichomonas foetus in mice glycolaldehyde-2,4-dinitro-phenylhydrazone acetate and 2,3-diacetylglycerolaldehyde-2,4-dinitro-phenylhydrazone exhibited an antiparasitic effect slightly inferior to that of tinidazole. Structure-activity relationships are discussed. On the basis of the results obtained the chemotherapeutic value of the mentioned substances seems to be promising.

• MeSH
• absces farmakoterapie   MeSH
• acetaldehyd * analogy a deriváty   MeSH
• antitrichomonádové látky chemická syntéza   MeSH
• diglyceridy chemická syntéza   farmakologie   MeSH
• glyceridy chemická syntéza   MeSH
• hydrazony chemická syntéza   farmakologie   MeSH
• myši MeSH
• peritonitida farmakoterapie   parazitologie   MeSH
• tinidazol terapeutické užití   MeSH
• trichomonádová vaginitida farmakoterapie   parazitologie   MeSH
• Trichomonas vaginalis účinky léků   MeSH
• trichomoniáza farmakoterapie   parazitologie   MeSH
• Tritrichomonas účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 2,3-di-O-acetylglyceroaldehyde-2,4-dinitrophenylhydrazone MeSH Prohlížeč
• acetaldehyd * MeSH
• antitrichomonádové látky MeSH
• diglyceridy MeSH
• glyceridy MeSH
• glycoaldehyde-2,4-dinitrophenylhydrazone acetate MeSH Prohlížeč
• hydrazony MeSH
• tinidazol MeSH