Novel indole-2-carboxylic acid analogues: Synthesis and a new light in to their antioxidant potentials

Naik, Nagaraja; Sharath, Vishwanath; Kumar, Hemant

doi:10.5155/eurjchem.3.2.214-219.588

Cited by 7 publications

(8 citation statements)

References 22 publications

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“…This study is a continuation of our previous study on the synthesis of new tetracyclic and pentacyclic nonlinear phenothiazine derivatives [ 28 , 29 ]. The synthesized phenothiazine derivatives, 6-chloro-11-azabenzo[a]phenothiazine-5-one and 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one, were transported from the Chemistry Laboratory of University of Nigeria Nsukka to the Chemistry Laboratory of Godfrey Okoye University, Enugu, Nigeria ( Figure 1 ).…”

Section: Methodsmentioning

confidence: 71%

“…Phenothiazines undergo reversible one-electron oxidation processes with low potentials which lead to stable and deeply coloured radical cations [ 39 ]. New phenothiazines derivatives have been shown to possess antioxidant activity [ 28 ]. This includes benzothiazines [ 40 ], azaphenothiazines, and phenothiazine-aryl amines conjugates via acetyl group [ 41 , 42 ].…”

Section: Resultsmentioning

confidence: 99%

“…Since then, these compounds have been of great pharmacological importance as they have been shown to possess various biological activities including antibacterial, antiviral, anti-inflammatory, and anticancer activities [ 25 – 27 ]. More so, phenothiazine structural motif has successfully been used in the design of a variety of pharmaceuticals which are clinically important for antioxidants activity, antitubercular activity, cholinesterase inhibitor, histamine H 1 antagonist, and multiple drug resistance (MDR) reverting agent [ 28 – 31 ]. Substitution of phenothiazines ring has a great influence on their chemical properties.…”

Section: Introductionmentioning

confidence: 99%

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Potential Antioxidant Activity of New Tetracyclic and Pentacyclic Nonlinear Phenothiazine Derivatives

Engwa

Ayuk

Igbojekwe

et al. 2016

Biochemistry Research International

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The global increase in oxidative stress related diseases such as cancer, cardiovascular, and inflammatory diseases caused by overwhelming level of free radicals in the body has encouraged the search for new antioxidant agents. Based on the ability of newly synthesized phenothiazine derivatives (6-chloro-11-azabenzo[a]phenothiazine-5-one and 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one) to oxidize H2O2, a known free radical to sulfoxide, this study assessed the in vitro and in vivo antioxidant activity. The synthesized phenothiazine derivatives exhibited reducing power potential to convert Fe3+ to Fe2+ and high ability to scavenge H2O2 free radical in vitro. These activities were comparable to ascorbic acid, a standard antioxidant. The catalase activity significantly increased (p < 0.05) in groups 1 and 2 animals that received the phenothiazine derivatives compared to the controls (groups 3 and 4) suggesting the ability of the phenothiazine derivatives to scavenge H2O2 in vivo. The malondialdehyde level in groups 1 and 2 animals was lower than that in group 3 that received the reference compound (ascorbic acid) and group 4 that received the solvent suggesting the ability of the phenothiazine derivatives to prevent lipid membrane damage. AST and bilirubin levels were higher in group 2 animals which received 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one compared to group 3, the positive control. The results suggest that phenothiazine derivatives, especially 6-chloro-11-azabenzo[a]phenothiazine-5-one, possess antioxidant activity though 6-[4-bromophenyl]-10-methyl-11-azabenzo[a]phenothiazine-5-one was slightly toxic. This activity may be due to the presence of electron donors such as sulfur as well as the richness of hydrogen in the additional benzene rings for substitution. Further study is needed to identify tolerable doses for possible therapeutic purposes.

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Section: Methodsmentioning

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Potential Antioxidant Activity of New Tetracyclic and Pentacyclic Nonlinear Phenothiazine Derivatives

Engwa

Ayuk

Igbojekwe

et al. 2016

Biochemistry Research International

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“…The residue was purified by column chromatography to give 1−5 (Scheme 1 and Table 2). 62 intermediate 1−5 in THF was added dropwise to the mixture of 1.2 mmol amine and K 2 CO 3 , and the mixture was heated under reflux until the starting material was consumed (determined by TLC, 6−8 h) (Scheme 1). Solvent was evaporated, and the residue was extracted with ethyl acetate.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Structure of Novel Phenothiazine Derivatives, and Compound Prioritization via In Silico Target Search and Screening for Cytotoxic and Cholinesterase Modulatory Activities in Liver Cancer Cells and In Vivo in Zebrafish

Kisla,

Yaman,

Zengin-Karadayi

et al. 2024

ACS Omega

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Phenothiazines (PTZ) are antipsychotics known to modulate a variety of neurotransmitter activities that include dopaminergic and cholinergic signaling and have been identified as potential anticancer agents in vitro. However, it is important to also test whether a highly cytotoxic, repurposed, or novel PTZ has low toxicity and neuromodulatory activity in vivo using vertebrate model organisms, such as zebrafish. In this study, we synthesized novel phenothiazines and screened them in vitro in liver cancer and in vivo in zebrafish embryos/larvae. The syntheses of several intermediate PTZ 10-yl acyl chlorides were followed by elemental analysis and determination of 1 H NMR and 13 C NMR mass (ESI + ) spectra of a large number of novel PTZ 10-carboxamides. Cytotoxicities of 28 PTZ derivatives (1−28) screened against Hep3B and SkHep1 liver cancer cell lines revealed five intermediate and five novel leads along with trifluoperazine (TFP), prochlorperazine (PCP), and perphenazine, which are relatively more cytotoxic than the basic PTZ core. Overall, the derivatives were more cytotoxic to Hep3B than SkHep1 cells. Moreover, in silico target screening identified cholinesterases as some of the commonest targets of the screened phenothiazines. Interestingly, molecular docking studies with acetylcholinesterase (AChE) and butyrylcholinesterase proteins showed that the most cytotoxic compounds 1, 3, PCP, and TFP behaved similar to Huprin W in their amino acid interactions with the AChE protein. The highly cytotoxic intermediate PTZ derivative 1 exhibited a relatively lower toxicity profile than those of 2 and 3 during the zebrafish development. It also modulated in vivo the cholinesterase activity in a dose-dependent manner while significantly increasing the total cholinesterase activity and/or ACHE mRNA levels, independent of the liver cancer cell type. Our screen also identified novel phenothiazines, i.e., 8 and 10, with significant cytotoxic and cholinesterase modulatory effects in liver cancer cells; yet both compounds had low levels of toxicity in zebrafish. Moreover, they modulated the cholinesterase activity or expression of ACHE in a cancer cell line-specific manner, and compound 10 significantly inhibited the cholinesterase activity in zebrafish. Accordingly, using a successful combination of in silico, in vitro, and in vivo approaches, we identified several lead anticancer and cholinesterase modulatory PTZ derivatives for future research.

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“…The literature survey approaching towards synthesis of sulphonamide linked pyrazole gathered with 5H-dibenz[b,f]azepine moiety indicates the lack of reference available. In view of these observation and in persistence of our earlier work on different bioactive heterocyclic derivatives [22][23][24][25][26], we envision our approach towards gathering two bioactive entities, 5H-dibenz[b,f]azepine and pyrazole sulphonamide in one compact structure for probing the antimicrobial and antioxidant potentials.…”

Section: Introductionmentioning

confidence: 99%

5H-Dibenz[b,f]azepine based pyrazole sulphonamides: A privileged platform for probing the antimicrobial and antioxidative properties

Kumar

Rangaswamy³

et al. 2015

Eur. J. Chem.

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Novel indole-2-carboxylic acid analogues: Synthesis and a new light in to their antioxidant potentials

Cited by 7 publications

References 22 publications

Potential Antioxidant Activity of New Tetracyclic and Pentacyclic Nonlinear Phenothiazine Derivatives

Potential Antioxidant Activity of New Tetracyclic and Pentacyclic Nonlinear Phenothiazine Derivatives

Synthesis and Structure of Novel Phenothiazine Derivatives, and Compound Prioritization via In Silico Target Search and Screening for Cytotoxic and Cholinesterase Modulatory Activities in Liver Cancer Cells and In Vivo in Zebrafish

5H-Dibenz[b,f]azepine based pyrazole sulphonamides: A privileged platform for probing the antimicrobial and antioxidative properties

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