3-METHOXY Aroylhydrazones – Free Radicals Scavenging, Anticancer and Cytoprotective Potency (original) (raw)
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Pharmaceuticals
A series of ten new hydrazide–hydrazone derivatives bearing a pyrrole ring were synthesized and structurally elucidated through appropriate spectral characteristics. The target hydrazones were assessed for radical scavenging activity through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) tests, with ethyl 5-(4-bromophenyl)-1-(2-(2-(4-hydroxy-3,5-dimethoxybenzylidene)hydrazine-yl)-2-oxoethyl)-2-methyl-1H-pyrrole-3-carboxylate (7d) and ethyl 5-(4-bromophenyl)-1-(3-(2-(4-hydroxy-3,5-dimethoxybenzylidene) hydra zine-yl)-3-oxopropyl)-2-methyl-1H-pyrrole-3-carboxylate (8d) highlighted as the best radical scavengers from the series. Additional density functional theory (DFT) studies have indicated that the best radical scavenging ligands in the newly synthesized molecules are stable, do not decompose into elements, are less polarizable, and with a hard nature. The energy of the highest occupied molecular orbital (HOMO) revealed that ...
Oriental Journal of Chemistry, 2016
A series of N-cinnamoyl aryl hydrazones 2a-2i were synthesized in good yields by microwave irradiation technique. The title compounds were formed by nucleophilic condensation of various N 1-substituted benzylidene-2-cyano aceto hydrazides with N,N-dimethyl amino benzaldehyde. The intermediate N 1-substituted benzylidene-2-cyano aceto hydrazide was obtained by condensing various substituted benzaldehydes with cyanoacetohydrazide. The structures of the compounds were characterized by IR, 1 H NMR and Mass spectra. The antioxidant activity was studied by reduction of DPPH, scavenging of nitric oxide and hydrogen peroxide methods with ascorbic acid as the standard drug. The compounds were evaluated for cytotoxic activity by BSLT method and their ED 50 values were compared the standard podophyllotoxin. Among the compounds evaluated, N 1-benzylidene-2cyano-3-(4-dimethylamino) phenyl acrylo hydrazide (2a) and N 1-(4-methoxy-benzylidene)-2-cyano-3-(4-dimethylamino) phenyl acrylohydrazide (2e) showed good antioxidant activity towards all the three models .The compounds 2a and 2e showed ED 50 values 3.07 µg/ml and 3.7 µg/ml respectively which were compared against the standard podophyllotoxin (1.64 µg/ml).
Synthesis, in vitro safety and antioxidant activity of new pyrrole hydrazones
Acta Pharmaceutica, 2020
, in vitro safety and antioxidant activity of new pyrrole hydrazones Six new N-pyrrolylhydrazide hydrazones were synthesized under micro synthesis conditions, assuring about 59-93 % yield, low harmful emissions and reagent economy. The structures of the new compounds were elucidated by melting points, TLC characteristics, IR, 1 H and 13 C NMR spectral data followed by MS data. The purity of the obtained compounds was proven by the corresponding elemental analyses. "Lipinski's rule of five" parameters were applied for preliminary evaluation of the pharmacokinetic properties of the target molecules. The initial in vitro safety screening for cytotoxicity (on HepG2 cells) and hemocompatibility (hemolysis assay) showed good safety of the new compounds, where ethyl 5-(4-bromophenyl)-1-(1-(2-(4-hydroxy-3-methoxybenzylidene)hydrazineyl)-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate (4d) and ethyl 5-(4-bromophenyl)-1-(1-(2-(2hydroxybenzylidene)hydrazineyl)-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate (4a) were the least toxic. The antioxidant activity in terms of radical scavenging activity (DPPH test) and reducing ability (ABTS) was also evaluated. The antioxidant protective potential of the compounds was next determined in different in vitro cellular-based models, revealing compounds 4d and 3 [ethyl 5-(4-bromophenyl)-1-(1-hydrazineyl-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate] as the most promising compounds, with 4d having better safety profile.
Journal of Drug Delivery and Therapeutics
A new isatin-hydrazone (I); N'-[(E)-(5-bromo-1H- indol-3-yl) methylidene] pyridine-4-carbohydrazide was prepared from the condensation reaction of 5-bromo-1H-indole-3-carbaldehyde and the anti-tubercular drug; isoniazid, in the presence of acetic acid. The obtained hydrazone was identified and characterized by physico-chemical techniques such as melting point, IR, NMR, and mass spectroscopy. In addition, the acute toxicity was evaluated using mice. The antioxidant of I was evaluated against superoxide anion radical. Our biological results indicate low toxicity of I at the high dose of 1000 mg/kg, and high superoxide anion scavenging effect with inhibition percentage of 82.57 % and IC50 138.78 µg/mL. Keyword: hydrazone, toxicity, antioxidant, superoxide anion
Antioxidant activity of some benzimidazole derivatives to definite tumor cell lines
Journal of Cancer Research & Therapy, 2013
A group of bis(benzimidazol-2-yl) amines have been already evaluated for cytotoxicity in vitro to human colorectal cancer cell line HT-29, breast cancer cells MDA-MB-231 and normal spleen cells and two of them (B1 and B2) have been taken for the purposes of our present investigations. From the second group of compounds representing 1,3-disubstituted-2,3-dihydro-2-iminobenzimidazoles two substances (B3 and B4) have been chosen because of their most pronounced anti-proliferative effect to human colorectal cancer cell line HT-29, breast cancer cells MDA-MB-231 and normal spleen cells, using the in vitro proliferative MTS-test. It was important to estimate the cause for this suppressive activity of the compounds. We proposed that this could be due to their antioxidant capacity. The substances were examined for antioxidant activity against hydroxyl and peroxyl radicals, applying the HORAC and ORAC methods and showed considerable capacity. The scavenging capacity of B2 towards hydroxyl radicals is the highest, followed by B1. It was estimated that B2 has the greatest scavenger capacity of oxygen radicals, emitted by the examined cells followed in descending order by B1, B3 and B4. The observed differences can be considered as impact of their structure on the Me 2-helating activity and effective H-atom donation. A correlation was observed between the structure of the particular substance and the expressed antioxidant potential. The latter correlated also with the effect on the tested tumor cell lines. This result means that tumor cells are accompanied by a measurable emission of ROS which might be regulated by a proper application of antioxidants.
Anticancer research
Chemically active molecules, such as reactive oxygen species (ROS), are prone to induce cellular damage by oxidative stress and this could be exploited as a strategy to kill malignant cells. In this study, we evaluated the antitumor activity of a new compound, N'-formyl-2-(5nitrothiophen-2-yl)benzothiazole-6-carbohydrazide (FBZC) by assessing its pro-oxidant effects on breast cancer in vitro. Oxidative stress, generated by FBZC, was characterized by measuring reactive species and antioxidant enzymes and markers. Results showed that the cytotoxic effects of FBZC on MCF7 breast cancer cells (half inhibitory concentration of 5.4 μg/ml), were partially reversed by the addition of regular antioxidants. FBZC induced ROS and lipid peroxidation, together with a significant inhibition of superoxide dismutase, glutathione reductase and total glutathione levels as well as increases in catalase and glutathione-S-transferase activities, in an acute fast response. Thus, the antitumor effects of FBZC could be related to oxidative deregulation due to a combination of induction of ROS generation and inhibition of key antioxidant enzymes.
Biochimica et biophysica acta, 2015
Salicylaldehyde isonicotinoyl hydrazone (SIH) is an iron chelator of the aroylhydrazone class that displays antioxidant or prooxidant effects in different mammalian cell lines. Because the liver is the major site of iron storage, elucidating the effect of SIH on hepatic oxidative metabolism is critical for designing effective hepatic antioxidant therapies. Hepatocyte-like HepG2 cells were exposed to SIH or to analogs showing greater stability, such as N'-[1-(2-Hydroxyphenyl)ethyliden]isonicotinoyl hydrazide (HAPI), or devoid of iron chelating properties, such as benzaldehyde isonicotinoyl hydrazone (BIH), and toxicity, oxidative stress and antioxidant (glutathione) metabolism were evaluated. Autoxidation of Fe(2+)in vitro increased in the presence of SIH or HAPI (but not BIH), an effect partially blocked by Fe(2+) chelation. Incubation of HepG2 cells with SIH or HAPI (but not BIH) was non-toxic and increased reactive oxygen species (ROS) levels, activated the transcription facto...
International journal of molecular and cellular medicine, 2015
The current study highlights the in vitro antioxidant and antitumor activity of the previously-synthesized hydrazone derivatives against various free radicals and human cancer cell lines, respectively. The anticancer efficacies of the compound were tested by measuring cytotoxicity in cancer cell lines HeLa, A549, and non-cancerous NL20 cells. Compounds possessing electron-donor methoxy and methyl substitutions at the para position of the phenyl ring moiety showed a concentration dependent free radical scavenging effects. The free radical-scavenging potential of synthetic compounds 11 and 14 may have significant impact on the prevention of free radical-induced oxidative stress and carcinogenesis. The results from cytotoxicity and cell migration assay showed that the substitution of electron-withdrawing fluoro, chloro and bromo functional groups induced a significant (P< 0.001) loss of cell viability and inhibited the invasive potential of the human cancer cells. Additionally, thes...
Toxicologic Pathology, 1987
Hydrazine derivatives are widely used in agriculture, in industry, as rocket propellants, and in medicine. Hydrazines also occur naturally in tobacco and mushrooms. Many hydrazines tested in animal studies appear to be carcinogenic and induce tumors in various target tissues in mice, hamsters, and rats. The use of hydrazine derivatives in humans is often complicated by adverse side-effects such as liver injury and rheumatoid arthritis. A number of studies have demonstrated that hydrazine derivatives are activated to reactive intermediates, such as free radicals, through a variety of cellular oxidative metabolic pathways. The aim of this work is to demonstrate the occurrence of free radical intermediates during the metabolic activation of various hydrazine derivatives and to characterize the enzymatic system($ responsible for the activation to free radical species. The hydrazines studied are acetylhydrazine, isoniazid, isopropylhydrazine, iproniazid, methylhydrazine, 1, I-dimethylhydrazine, and 1,2-dimethylhydrazine. The model systems chosen are those of rat liver microsomes and isolated hepatocytes. Free radical intermediates have been demonstrated by the electron spin resonance spectroscopy coupled to spin trapping technique. The activation mechanism has been characterized using inhibitors ofthe mixed function oxidase system and ofthe FAD-dependent oxygenase system. Glutathione was able to scavenge, with high efficiency, the free radicals produced.
Russian Journal of Bioorganic Chemistry, 2020
In this research, a series of hydrazine-hydrazone derivatives (Ia-g), (IIa-h) were synthesized to discover new antioxidant and anticholinesterase agents. The structures of synthesized compounds were characterized by spectroscopic data using UV, IR, 1 H, 13 C NMR, mass spectroscopy, and elemental analysis. The bio-evaluation of the synthesized compounds (Ia-g), (IIa-h) were evaluated according to in vitro activity assays. The results of β-carotene/linoleic acid assay showed that among the synthesized compounds, the (Ib), (Ie), (IIb-IIe), and (IIh) compound exhibited higher activity for the lipid peroxidation inhibitory activity. In the DPPH free scavenging activity and the cation radical scavenging activity in ABTS •+ activity, compound (IIb) was found to be more active. In the CUPRAC reduced power assay, the A 0.5 values of all synthesized compounds were better than α-TOC. In AChE assay, compound (IIb) exhibited the most activity with IC 50 = 11.12 ± 0.74 μM, while the compounds (Ib-g) and (IIb-h), exhibited excellent activity than the positive standard galantamine (IC 50 = 46.06 ± 0.10 μM) in the BChE assay.