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

Antiprotozoal effects of hydrazones derived from compounds with 1 to 4 carbon atoms were studied on the model organism Trichomonas vaginalis isolated from a female patient with acute urogenital trichomoniasis.

• MeSH
• antiprotozoální látky farmakologie   MeSH
• hydrazony farmakologie   MeSH
• metronidazol farmakologie   MeSH
• Trichomonas vaginalis účinky léků   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• antiprotozoální látky MeSH
• hydrazony MeSH
• metronidazol MeSH

Based on the broad spectrum of biological activity of hydrazide-hydrazones, trifluoromethyl compounds, and clinical usage of cholinesterase inhibitors, we investigated hydrazones obtained from 4-(trifluoromethyl)benzohydrazide and various benzaldehydes or aliphatic ketones as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). They were evaluated using Ellman's spectrophotometric method. The hydrazide-hydrazones produced a dual inhibition of both cholinesterase enzymes with IC50 values of 46.8-137.7 µM and 19.1-881.1 µM for AChE and BuChE, respectively. The majority of the compounds were stronger inhibitors of AChE; four of them (2-bromobenzaldehyde, 3-(trifluoromethyl)benzaldehyde, cyclohexanone, and camphor-based 2o, 2p, 3c, and 3d, respectively) produced a balanced inhibition of the enzymes and only 2-chloro/trifluoromethyl benzylidene derivatives 2d and 2q were found to be more potent inhibitors of BuChE. 4-(Trifluoromethyl)-N'-[4-(trifluoromethyl)benzylidene]benzohydrazide 2l produced the strongest inhibition of AChE via mixed-type inhibition determined experimentally. Structure-activity relationships were identified. The compounds fit physicochemical space for targeting central nervous systems with no apparent cytotoxicity for eukaryotic cell line together. The study provides new insights into this CF3-hydrazide-hydrazone scaffold.

• Klíčová slova
• 4-(trifluoromethyl)benzohydrazide, acetylcholinesterase inhibition, butyrylcholinesterase inhibition, enzyme inhibition, hydrazides, hydrazones,
• MeSH
• acetylcholinesterasa metabolismus   MeSH
• butyrylcholinesterasa metabolismus   MeSH
• centrální nervový systém účinky léků   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• hematoencefalická bariéra účinky léků   patologie   MeSH
• hydraziny chemie   MeSH
• hydrazony chemie   farmakologie   MeSH
• kinetika MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• butyrylcholinesterasa MeSH
• cholinesterasové inhibitory MeSH
• hydraziny MeSH
• 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

We report design and synthesis of set of novel anticancer agents based on caffeine-hydrazones bearing 2-hydroxyaryl- or 2-N-heteroaryl moiety. Anticancer activity evaluation using seven cancer cell lines and two non-malignant cell lines demonstrated that several derivatives display significant anticancer activity and great selectivity index toward T-lymphoblastic leukaemia cells. In general, hydrazones bearing 2-N-heteroaryl moiety are more active and selective than those with 2-hydroxyaryl moiety. Tested compounds exhibit dose-dependent inhibition of both RNA and DNA synthesis, with some exceptions. Antimicrobial activities were tested on set of twelve bacterial and yeast strains, however prepared compounds were not active, suggesting for a molecular target specific for eukaryotic cells.

• Klíčová slova
• Anticancer agents, Caffeine–hydrazones, Cancer treatment, Leukaemia, Selectivity,
• MeSH
• akutní lymfatická leukemie farmakoterapie   MeSH
• antiinfekční látky chemie   farmakologie   MeSH
• antitumorózní látky chemie   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• Bacteria účinky léků   MeSH
• buněčné linie MeSH
• houby účinky léků   MeSH
• hydrazony chemie   farmakologie   MeSH
• kofein chemie   farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiinfekční látky MeSH
• antitumorózní látky MeSH
• hydrazony MeSH
• kofein MeSH

Hydrazide-hydrazones have been described as a scaffold with antimicrobial and cytotoxic activities as well as iodinated compounds. A resistance rate of bacterial and fungal pathogens has increased considerably. That is why we synthesized and screened twenty-two iodinated hydrazide-hydrazones 1 and 2, ten 1,2-diacylhydrazines 3 and their three reduced analogues 4 for their antibacterial, antifungal, and cytotoxic properties. Hydrazide-hydrazones were prepared by condensation of 4-substituted benzohydrazides with 2-/4-hydroxy-3,5-diiodobenzaldehydes, diacylhydrazines from identical benzohydrazides and 3,5-diiodosalicylic acid via its chloride. These compounds were investigated in vitro against eight bacterial and eight fungal strains. The derivatives were found potent antibacterial agents against Gram-positive cocci including methicillin-resistant Staphylococcus aureus with the lowest values of minimum inhibitory concentrations (MIC) of 7.81 µM. Four compounds inhibited also human pathogenic fungi (MIC of ≥1.95 µM). The derivatives had different degrees of cytotoxicity for HepG2 and HK-2 cell lines (IC50 values from 11.72 and 26.80 µM, respectively). Importantly, normal human cells exhibited lower sensitivity. The apoptotic effect was also investigated. In general, the presence of 3,5-diiodosalicylidene scaffold (compounds 1) is translated into enhanced both antimicrobial and cytotoxic properties whereas its 4-hydroxy isomers 2 share a low biological activity. N'-Benzoyl-2-hydroxy-3,5-diiodobenzohydrazides 3 have a non-homogeneous activity profile. Focusing on 4-substituted benzohydrazide part, the presence of an electron-withdrawing group (F, Cl, CF3, NO2) was found to be beneficial.

• Klíčová slova
• 1,2-diacylhydrazines, Antibacterial activity, Antifungal activity, Apoptosis, Cytotoxicity, Hydrazides, Hydrazones, Iodinated compounds, Methicillin-resistant Staphylococcus aureus,
• MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• antifungální látky chemie   farmakologie   MeSH
• antitumorózní látky chemie   farmakologie   MeSH
• Bacteria účinky léků   MeSH
• buňky Hep G2 MeSH
• houby účinky léků   MeSH
• hydraziny chemie   MeSH
• hydrazony chemie   MeSH
• lidé MeSH
• objevování léků MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• antifungální látky MeSH
• antitumorózní látky MeSH
• hydraziny MeSH
• hydrazony MeSH

• MeSH
• antibakteriální látky * MeSH
• Bacillus účinky léků   růst a vývoj   MeSH
• Escherichia coli účinky léků   růst a vývoj   MeSH
• hydrazony farmakologie   MeSH
• Micrococcus účinky léků   růst a vývoj   MeSH
• sacharidy MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• hydrazony MeSH
• sacharidy MeSH

Several new fluorine-containing hydrazones were synthesized and screened for their in vitro antimycobacterial activity. Nine of these derivatives have shown a remarkable activity against MDR-TB strain with MIC 0.5 μg/mL and high value of selectivity index (SI). Compound 3h with the highest SI (1268.58) was used for stability evaluation with putative metabolites (ciprofloxacin and formylciprofloxacin) detection. Compound 3h was stable at pH 7.4 of aqueous buffer and rat plasma, in acidic buffers (at pH 3 and 5) slow decomposition was observed. Interestingly, no formylciprofloxacin was detected in the solution, and only slightly increased concentration of ciprofloxacin was observed instead. Trifluoromethyl hydrazones 3f and 3g exhibited the best activity also against two strains of Mycobacterium kansasii (MIC 1-4 μmol/L). All evaluated compounds were found to be non-cytotoxic.

• MeSH
• antituberkulotika chemie   metabolismus   farmakologie   MeSH
• buněčné linie MeSH
• fluor chemie   metabolismus   farmakologie   MeSH
• hydrazony chemie   metabolismus   farmakologie   MeSH
• krevní plazma metabolismus   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• multirezistentní tuberkulóza farmakoterapie   MeSH
• Mycobacterium kansasii účinky léků   MeSH
• Mycobacterium účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antituberkulotika MeSH
• fluor MeSH
• hydrazony 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

Novel aromatic hydrazones derived from pyridoxal isonicotinoyl hydrazone (PIH) are interesting compounds from the viewpoint of their pharmacodynamic activity. However, they were recently shown to suffer from relatively short biological half-lives. The purpose of the present study was to investigate the stability of novel aroylhydrazones in plasma and related biological media in order to reveal its potential involvement in the pharmacokinetics of these drugs. Three different aroylhydrazones (pyridoxal isonicotinoyl hydrazone - PIH, salicylaldehyde isonicotinoyl hydrazone - SIH and pyridoxal 2-chlorobenzoyl hydrazone - o-108) were incubated in plasma from different species, plasma ultrafiltrate, bovine serum albumin, RPMI cell medium and phosphate buffer saline (PBS) at 37 degrees C. Stability of these compounds was determined using precise, selective and validated HPLC methods. Although the aroylhydrazones were relatively stable in PBS, they underwent rapid degradation in plasma. Plasma proteins as well as low molecular weight components were involved in this matter. Furthermore, the products of hydrazone bond splitting revealed in this study were also found in the chromatograms from pharmacokinetic experiments. In the light of short biological half-lives determined in vivo, these in vitro findings strongly suggest that hydrolysis of investigated aromatic hydrazones in plasma could have a significant impact on their pharmacokinetics. Furthermore, these results also suggest that plasma stability of other novel drug candidates containing the hydrazone bond deserves to be considered.

• MeSH
• aldehydy krev   chemie   MeSH
• chelátory železa chemie   MeSH
• fosfáty chemie   MeSH
• hemofiltrace MeSH
• hydrazony krev   chemie   MeSH
• isoniazid analogy a deriváty   krev   chemie   MeSH
• koncentrace vodíkových iontů MeSH
• králíci MeSH
• kultivační média chemie   MeSH
• molekulární struktura MeSH
• poločas MeSH
• pufry MeSH
• pyridoxal analogy a deriváty   krev   chemie   MeSH
• sérový albumin hovězí chemie   MeSH
• skot MeSH
• stabilita léku MeSH
• teplota MeSH
• vysokoúčinná kapalinová chromatografie přístrojové vybavení   metody   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• aldehydy MeSH
• chelátory železa MeSH
• fosfáty MeSH
• hydrazony MeSH
• isoniazid MeSH
• kultivační média MeSH
• pufry MeSH
• pyridoxal 2-chlorobenzoyl hydrazone MeSH Prohlížeč
• pyridoxal isonicotinoyl hydrazone MeSH Prohlížeč
• pyridoxal MeSH
• salicylaldehyde isonicotinoyl hydrazone MeSH Prohlížeč
• sérový albumin hovězí MeSH