Synthesis and antileishmanial activity of novel pyridinium-hydrazone derivatives

Alptüzün, Vildan; Cakiroglu, Gokcer; Limoncu, M. Emin; Eraç, Bayrı; Hoşgör-Limoncu, Mine; Erciyas, Erçin

doi:10.3109/14756366.2012.697058

Cited by 12 publications

(9 citation statements)

References 48 publications

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“…23) The structures of the compounds (1a-3c) were identified by IR, 1 H-NMR, 13 C-NMR and the purity levels of the compounds were confirmed by high resolution (HR)-MS analysis. The spectroscopic properties were in accordance with the proposed structures.…”

Section: Resultsmentioning

confidence: 99%

“…Chemistry The synthesis of arylidenehydrazinylpyridinium derivatives was carried out according to the literature 22,23) as summarized in Chart 1. In the first step, 4-hydrazinylpyridine was obtained by nucleophilic substitution of hydrazine with 4-chloropyridine then corresponding hydrazone derivatives 1-3 were furnished by the condensation of 4-hydrazi-nylpyridine with aromatic ketones in ethanol under reflux.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis, Biological Evaluation and Molecular Docking Study of Hydrazone-Containing Pyridinium Salts as Cholinesterase Inhibitors

Parlar

Bayraktar

Tarikogullari

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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A series of pyridinium salts bearing alkylphenyl groups at 1 position and hydrazone structure at 4 position of the pyridinium ring were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. The cholinesterase (ChE) inhibitory activity studies were carried out by using the Ellman's colorimetric method. All compounds displayed considerable AChE and BuChE inhibitory activity and some of the compounds manifested remarkable anti-AChE activity compared to the reference compound, galantamine. Among the title compounds, the series including benzofuran aromatic ring exhibited the best inhibitory activity both on AChE and BuChE enzymes. Key words acetylcholinesterase inhibitor; butyrylcholinesterase inhibitor; docking study; pyridinium salt; hydrazone Acetylcholinesterase (AChE) is an enzyme which is responsible for the hydrolysis of acetylcholine (ACh).1) AChE inhibitors bind to the enzyme thereby increases the level of acetylcholine by inhibiting the hydrolysis of ACh to choline and acetate.2) AChE inhibitors are used as therapeutic agents in the treatment of disorders related to ACh diminution such as Alzheimer disease, myasthenia gravis, glaucoma.3) AChE has a deep, narrow gorge approximately 20 Å long. Catalytic active site (CAS) of the enzyme is located at the bottom of the gorge whereas peripheral anionic site (PAS) is at the entrance. 4) Although anti-AChE drugs show a wide range of chemical diversity, they generally include aromatic-heterocyclic ring systems and a nitrogen atom as chemical structure (Fig. 1). These structures have an important role for the interaction with specific amino acids in the enzyme.5) Aromaticheterocyclic nuclei generally have potential hydrophobic and charge-transfer interaction, while nitrogen atom and its quaternary form can make hydrogen or ionic bonds as well as dipole-dipole or ion-dipole interactions with amino acids in the enzyme gorge.5-10) In addition, quaternary nitrogen cation displays highly positive binding stabilization due to cation-π interactions with amino acid residues in AChE enzyme. [9][10][11][12] Many reports indicated that compounds bearing aromatic/ heteroaromatic rings on lateral parts of pyridinium displayed high AChE inhibitory activity and act as dual binding inhibitors. [13][14][15][16] According to the docking studies of these compounds, it was found that both terminal rings attached to the pyridinium were able to bind simultaneously to both CAS and PAS of the enzyme resulting in higher AChE inhibitory activity. [13][14][15][16] Among the reported studies, pyridinium derivatives having benzofuran ring were shown to have a significant AChE inhibitory activity and it was observed that benzofuran and phenyl moieties as terminal rings were interacted with both PAS and CAS of AChE. 15,16) On the other hand, many of compounds bearing hydrazonehydrazide functional group have been reported to possess ChE inhibitory activity. 17,18) The hydrazones have hydrogen donor and acceptor nitrogen atoms an...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Synthesis, Biological Evaluation and Molecular Docking Study of Hydrazone-Containing Pyridinium Salts as Cholinesterase Inhibitors

Parlar

Bayraktar

Tarikogullari

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…[26] on farklı kinolanhidrazonhibridini, Alptüzün ve ark. [30] pyridinium hydrazone derivelerini, Al-Kahraman ve ark. [31] N-unsubstituted hidrazon yapıdaki 3 (benzilmonohydrazones) ve 5 (benzophenonehydrazones) bileşiklerini ve Coimbra ve ark.…”

Section: Tartişma Ve Sonuçunclassified

Investigation of Anti-leishmanial Activity of the Ten Different Hydrazone Derivatives

Direkel¹,

Utku²,

Şahi̇n³

et al. 2016

Kafkas Univ Vet Fak Derg

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ÖzetLeishmaniasis Türkiye ve dünyada önemli paraziter bir hastalıktır. Leishmaniasis tedavisinde sodyum stibogluconate, miltefosin, paramomisin, amfoterisin B ve pentamidin gibi anti-leishmanial ilaçlar kullanılmaktadır. Fakat leishmaniasisin kemoterapisinde kullanılan bu ilaçların nefrotoksik, hepatotoksik ve teratojenik yan etkileri görülebilmektedir. Ayrıca antimon bileşiklerine karşı direnç gelişmesi nedeniyle de yeni terapötik ajanların keşfedilmesi ve geliştirilmesine öncelik verilmesi gerektiği düşünülmüştür. Bu çalışmanın amacı, sentezlenmiş hidrazon yapısındaki on farklı bileşiğin (5a-5j) Leishmania infantum promastigotlarına karşı anti-leishmanial aktivitesinin mikrodilüsyon yöntemiyle belirlenmesidir. Hazırlanan hidrazon bileşikleri, konsantrasyonu 6 µg/ml olacak şekilde RPMI-1640 besiyerlerine eklenmiş ve bileşiklerin mikroplakta konsantrasyon aralığı 3 -0.003 µg/ml olacak şekilde seri dilüsyonları yapılmıştır. Mikroplaklarda mikrodilüsyon besiyeri yöntemi uygulanarak, üzerine hemositometrede hücre sayısı 2.5x10 7 hücre/ml olacak şekilde ayarlanmış standart Leishmania infantum promastigotları eklenerek 27°C'de inkübe edilmiştir. Yirmi saat sonra mikroplakların üzerine alamar mavisi eklenerek 4 saat inkübe edilmiştir. Promastigotların üremesi 24, 48 ve 72. saatlerde değerlendirilmiştir. Kuyucuklarda rengin maviden pembeye dönmesi parazitin ürediği, rengin değişmeden kalması ise parazitin üremediği şeklinde değerlendirilmiştir. Bu çalışmada, Leishmania infantum promastigotlarına karşı en etkili maddelerin 5e, 5g ve 5h bileşikleri (MİK 0.187 µg/ml) olduğu, en etkisiz bileşiğin ise 5i bileşiği (MİK 3 µg/ml) olduğu saptanmıştır. Sentezlenen bileşiklerin ilaç olarak kullanılabilmesi için; gerekli olduğu düşünülen in vitro makrofaj kültüründe Leishmania amastigotlarına karşı etkinliği ve in vivo olarak deneysel hayvan modellerinde kontrol çalışmalarına ihtiyaç vardır. Anahtar sözcükler: Leishmania infantum, Hidrazon, Anti-leismanial aktivite, Alamar mavisi Investigation of Anti-leishmanial Activity of the Ten Different Hydrazone Derivatives AbstractLeishmaniasis is an important parasitic disease in Turkey and the world. Anti-leishmanial drugs such as sodium stibogluconate, miltefosine, paramomycin, amphotericin B, and pentamidine are used for the treatment of leishmaniasis. However, the drugs, used for the chemotheraphy of leishmaniasis, have some side effects such as nephrotoxicity, hepatotoxicity, and teratogenicity. In addition, it is deemed that the discovery and development of the new therapeutic agents must be given priority due to the development of resistance against antimony compounds. The purpose of this study is detecting the anti-leishmanial activity of ten different synthesized hydrazone compounds against Leishmania infantum promastigotes via the microdilution method. The prepared hydrazone compounds, having the concentration of 6 µg/ml, were added to RPMI-1640 media and the dilution of the hydrazone derivates was performed in the wells of microplates in the range of concentrations of 3 -0.003 ...

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“…[5] Autophagic defect may constitute metabolic stress, genetic damage susceptibility, and later cancer-promoting environment in cells. [30][31][32] On the other hand, 1,4-dihydropyridine derivatives obtained from a new series pyridinium-hydrazones using appropriate base [33] were evaluated as AChE inhibitory activity by our group. Thus, autophagy has a context-dependent role in cancer, and both induction and inhibition of autophagy may be the target of cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of pyridinium‐hydrazone derivatives as potential antitumoral agents

et al. 2018

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The hydrazones of 4-hydrazinylpyridinium bearing alkylphenyl groups on pyridinium nitrogen were synthesized and evaluated for their cytotoxic activity against MCF-7, PC3, U2OS, and HEK293 cell lines by Wst1 cell proliferation assay. Cytotoxic activity results indicated that d derivatives having butylene chain; 4 and 5 series having naphthalene and anthracene ring systems showed high cytotoxic activity (IC = 3.27-8.54 μm) on cancer cells. 3d (4-(2-(4-hydroxybenzylidene)hydrazinyl)-1-(4-phenylbutyl)pyridinium bromide) was the most cytotoxic compound with IC value of 3.27 μm against MCF-7. The most active derivatives (1d, 2d, 3d, 4, and 5 series) were selected to investigate for the effects on autophagy by analyzing the expression of autophagy marker proteins. The conversion of LC3-I to its lipidated form LC3-II is essential for autophagy and related to autophagosomes. According to our results, all tested compounds except for 3d induced lipidated form LC3-II accumulation. Then, the effects of the compounds on p62 protein level were also analyzed by the immunoblotting as the autophagy inhibition results in accumulation of p62. Further molecular mechanistic studies including morphological analysis and live-death assays indicated that all tested compounds (1d, 2d, 3d, 4, and 5 series) are potent antitumoral molecules and all except for 3d have potential to inhibit autophagic flux.

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Synthesis and antileishmanial activity of novel pyridinium-hydrazone derivatives

Cited by 12 publications

References 48 publications

Synthesis, Biological Evaluation and Molecular Docking Study of Hydrazone-Containing Pyridinium Salts as Cholinesterase Inhibitors

Synthesis, Biological Evaluation and Molecular Docking Study of Hydrazone-Containing Pyridinium Salts as Cholinesterase Inhibitors

Investigation of Anti-leishmanial Activity of the Ten Different Hydrazone Derivatives

Synthesis and evaluation of pyridinium‐hydrazone derivatives as potential antitumoral agents

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