Synthesized Chalcone Derivatives Research Articles

DFT analysis on spectral and NLO properties of (2E)-3-[4-(dimethylamino) phenyl]-1-(naphthalen-2-yl) prop-2-en-1-one; a d-π-A chalcone derivative and its docking studies as a potent hepatoprotective agent

Abstract The optimization and spectral (IR, 1H and 13C NMR) analysis of the synthesized chalcone derivative (2E)-3-[4-(dimethylamino) phenyl]-1-(naphthalen-2-yl) prop-2-en-1-one was carried out using DFT B3LYP/6-311G (d,p) method and compared with experimental results. The GIAO method was used to calculate 1H and 13C chemical shift. The βtot value was calculated by CAM-B3LYP method. Experimental SHG efficiency of DANP was analysed. TD-DFT method was used for absorption spectral analysis and compared with experimental result. The experimental and theoretical band gap was analysed. NBO analysis explains the molecular interactions; MEP plot was also performed. Molecular docking on hepatoprotective ability of title molecule with four different proteins was conducted and compared with most commonly used hepatoprotective drug silymarin.

New chalcone derivative exhibits antiproliferative potential by inducing G2/M cell cycle arrest, mitochondrial-mediated apoptosis and modulation of MAPK signalling pathway

In the present study, we investigated antiproliferative activity of seven newly synthesized chalcone derivatives. Among tested compounds, (2 E)-3-(acridin-9-yl)-1-(2,6-dimethoxyphenyl)prop-2-en-1-one (1C) was the most potent with IC50 = 4.1 μmol/L in human colorectal HCT116 cells and was selected for further studies. Inhibition of cell proliferation was associated with cell cycle arrest in G2/M phase and dysregulation of α, α1 and β5 tubulins. Moreover, 1C caused disruption of the mitochondrial membrane potential and increased number of cells with sub G0/G1 DNA content which is considered as marker of apoptosis. Apoptosis was confirmed by annexin V/PI and AO/PI staining. Furthermore, we found increased concentration of cytochrome c, Smac/Diablo and increased caspase-3 and caspase-9 activity, cleavage of PARP as well as activation of DNA repair mechanisms in 1C-treated HCT116 cancer cells. Moreover this chalcone derivative up-regulated proapoptotic Bax expression and down-regulated antiapoptotic Bcl-2 and Bcl-xL expression. Additionally, 1C treatment led to modulation of MAPKs and Akt signalling pathways.In conclusion, our data showed ability of 1C to suppress cancel cell growth and provide the rationale for further in vivo study.

Green approach for the synthesis of chalcone (3-(4-fluorophenyl)-1-(4-methoxyphenyl) prop-2-en-1-one) using concentrated solar radiation

The present work deals with the green solar assisted synthesis of chalcone (3-(4-fluorophenyl)-1-(4-methoxyphenyl)-prop-2-en-1-one). To check the efficacy of the process, chalcone has been synthesized by photochemical (UV radiation), thermal method (60°C) and the conventional method. The effect of catalyst concentration and temperature on the yield of the product has been studied. The synthesized chalcone derivative was characterised using Fourier Transform Infrared (FTIR) Spectroscopy, Liquid chromatography–mass spectrometry (LCMS) elemental analysis, X-ray diffraction analysis (XRD) and thermal analysis (TG/DTA). The time required for the completion of the reaction using solar assisted method and conventional method were 10min and 240min (4h), respectively. The crystallinity of material produced using concentrated solar radiation (CSR) was 14.16% higher than the conventional method. The amount of energy required to produce chalcone using CSR is 90.37% less energy than the conventional method. CSR was found to be green, simple and energy efficient novel idea for the synthesis of chalcone.

First principles study for the key electronic, optical and nonlinear optical properties of novel donor-acceptor chalcones

Using first-principle methods, several key electronic, optical and nonlinear optical properties are calculated for two recently synthesized chalcone derivatives i.e. (2E)-3-(4-methylphenyl)-1-(3-nitrophenyl)prop-2-en-1-one (comp.1) and (2E)-3-[4-(dimethylamino)phenyl]-1-(3-nitrophenyl)prop-2-en-1-one (comp.2). The calculation of dipole moment, polarizability <α>, anisotropy of polarizability as well as second hyperpolarizability (usually considered as a signature for two photon absorption phenomenon) are performed using density functional theory methods at PBE0/6-311G** level of theory. The linear average polarizability <α> for comp.1 and comp.2 are found to be 32.15×10−24 and 38.76×10−24esu, respectively. Similarly, the second hyperpolarizability <γ> amplitudes of comp.1 and comp.2 are found to be reasonably larger mounting to 79.31×10−36 and 181.36×10−36esu, respectively. The importance of donor end is determined by comparing p-methylphenyl group of comp.1 with that of N,N-dimethylaniline group of comp.2 that results a remarkable increase in its <γ> amplitude, which is ∼2 times larger as compared with that of comp.1 owing to the stronger donor-acceptor configuration of comp.2. Interestingly, a comparison of average static third-order nonlinear polarizabilities <γ> shows that <γ> amplitudes of comp.1 and comp.2 are ∼13 times and ∼29 times larger than that of para-nitroaniline (a typical standard push-pull NLO-phore) at the same PBE0/6-311G** level of theory, which indicates a real time NLO application of our titled compounds. Time dependent density functional theory (TD-DFT) calculations along with frontier molecular orbitals, density of states (DOS), second hyperpolarizability density analysis and molecular electrostatic potential (MEP) diagrams are used to trace the origin of electro-optical as well as structure property relationships.

Cholinesterases inhibition and molecular modeling studies of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones

Super-activation of cholinesterases (acetylcholinesterase and butyrylcholinesterase) are linked to various neurological problems most precisely Alzheimer's disease (AD), which leads to senile dementia. Therefore, cholinesterases (AChE & BChE) inhibition are considered as a promising strategy for the treatment of Alzheimer's disease. FDA approved drugs for the treatment of AD, belong to a group of cholinesterase inhibitors. However, none of them is able to combat or completely abrogate the disease progression. Herein, we report a series of newly synthesized chalcone derivatives with anti-AD potential. For this purpose, a series of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones were tested for their cholinesterases (AChE & BChE) inhibitory activity. All compounds were found as selective inhibitor of AChE. In piperidyl chalcones derivatives compound 1e having IC50 of 0.16 ± 0.008 μM and 2m in 2-pyrazoline chalcones with IC50 of 0.13 ± 0.006 μM, were found to be the most potent inhibitors of AChE, exhibiting ≈142 and ≈ 173-fold greater inhibitory potential compared to the reference inhibitor i.e., Neostigmine (IC50 ± SEM = 22.2 ± 3.2 μM). Molecular docking studies of most potent inhibitors were carried out to investigate the binding interactions inside the active site. Molecular docking study revealed that potent compounds and co-crystalized ligand had same binding orientation within the active site of target enzyme. Most of these compounds are selective inhibitors of AChE with a potential use against progressive neurodegenerative disorder and age related problems.

Inhibition of tyrosinase activity and melanin production by the chalcone derivative 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone

Abnormal accumulation of melanin pigments in the skin can be lead to hyperpigmentation disorders and melanoma. Melanin biosynthesis is ultimately regulated by the rate-limiting enzyme tyrosinase. In the present study, we synthesized chalcone derivatives and identified 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone (chalcone-21) as an anti-melanogenic substance in B16F10 melanoma cells. Chalcone-21 strongly inhibited cellular melanin production and tyrosinase activity in B16F10 melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH) or protoporphyrin IX. In addition, the compound suppressed not only the expression of tyrosinase, tyrosinase-related protein-1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF), but also the transcriptional activity of tyrosinase and MITF. Our results demonstrated chalcone-21 to be an effective depigmenting agent.

Tuning the push–pull configuration for efficient second-order nonlinear optical properties in some chalcone derivatives

Using the density functional theory methods, we effectively tune the second-order nonlinear optical (NLO) properties in some chalcone derivatives. Various unique push–pull configurations are used to efficiently enhance the intramolecular charge transfer process over the designed derivatives, which result in significantly larger amplitudes of the first hyperpolarizability as compared to their parent molecule. The ground state molecular geometries have been optimized using B3LYP/6-311G** level of theory. A variety of methods including B3LYP, CAM-B3LYP, PBE0, M06, BHandHLYP and MP2 are tested with 6-311G** basis set to calculate the first hyperpolarizability of parent system 1. The results of M06 are found closer to highly correlated MP2 method, which has been selected to calculate static and frequency dependent first hyperpolarizability amplitudes of all selected systems. At M06/6-311G** level of theory, the permanent electronic dipole moment (μtot), polarizability (α0) and static first hyperpolarizability (βtot) amplitudes for parent system 1 are found to be 5.139 Debye, 274a. u. and 24.22×10−30esu, respectively. These amplitudes have been significantly enhanced in designed derivatives 2 and 3. More importantly, the (βtot) amplitudes of systems 2 and 3 mount to 75.78×10−30 and 128.51×10−30esu, respectively, which are about 3 times and 5 times larger than that of their parent system 1. Additionally, we have extended the structure-NLO property relationship to several newly synthesized chalcone derivatives. Interestingly, the amplitudes of dynamic frequency dependent hyperpolarizability μβω (SHG) are also significantly larger having values of 366.72×10−48, 856.32×10−48 and 1913.46×10−48esu for systems 1–3, respectively, at 1400nm of incident laser wavelength. The dispersion behavior over a wide range of change in wavelength has also been studied adopting a range of wavelength from 1907 to 544nm. Thus, the present work realizes the potential of designed derivatives as efficient NLO-phores for modern NLO applications.

Virucidal Activity of Newly Synthesized Chalcone Derivatives against H1N1 Virus Supported by Molecular Docking and Membrane Interaction Studies

Oseltamivir and zanamivir are the commercially successful neuraminidase (NA) inhibitors approved for treatment of influenza, caused by highly pathogenic H1N1 influenza virus. Being transition state analogs of sialic acid, an endogenous ligand of NA, many scaffolds were developed based on similar structural features. But high rate of mutation in H1N1 necessitates extra search of a novel drug which can withstand drug resistance. Considering this we have developed a known naturally occurring scaffold chalcone, which is not a transition state analog, by incorporating various substituents based on their electronic and steric properties. With the help of computational drug design few promising molecules are screened and synthesized further. All the compounds under study showed different mode of binding in the active cavity. The inhibition of cytopathic effect of H1N1 by synthesized derivatives has been evaluated by in vitro cell based technique using oseltamivir as a standard. To gain insight into molecular mechanism of interaction of the derivatives with H1N1-NA, we have investigated the effect of these molecules on thermotropic properties and organization of membrane bilayer prepared from lipids using nuclear magnetic resonance (NMR) and differential scanning calorimetric (DSC) techniques. The compounds under study point towards stabilization of the membrane bilayer as expected for antiviral activity. Almost all derivatives showed activity parallel to the standard. Among all derivative ChmN showed highest activity at 0.67 nM whereas lowest activity was displayed by derivative ChmM at 10.35 nM. Derivative ChpH showed activity almost equivalent to oseltamivir.

QSAR of Chalcones Utilizing Theoretical Molecular Descriptors.

The paper is an attempt for QSAR modeling based on topological, electrostatic, quantum chemical, constitutional, geometrical and physicochemical indices computed from the structures of 59 set of synthesized chalcone derivatives tested for the cell cycle inhibition of mitotic G2/M phase using multiple linear regression method. Impact of such computed structural descriptors towards antimitotic and antiproliferative activities was analysed by ridge regression (RR) studies. The RR model explained that the topological indices alone can produce significant influence upon the pharmacological responses while combination of topological, electrostatic and quantum chemical descriptors can enhance the degree of impact towards antimitotic and antiproliferative activities of these compounds. Furthermore, QSAR models were formulated utilizing only topological and the combination of topological, electrostatic and quantum chemical descriptors respectively by multiple linear regression method and the validation of the model was performed by searching the predictability of the QSAR models. Satisfactory results were obtained in terms of model quality expressed as R(2) = 0.826, QLoo(2) = 0.710, Rpred(2) = 0.771 respectively for the topological indices. Combination of topological, electrostatic and quantum chemical descriptors resulted in an increase of R(2) = 0.965, QLoo 2 = 0.891, Rpred(2) = 0.849. The generated model predicted that BCUT descriptors (Charge) using modified partial equalization of orbital electronegativity (MPEOE), autocorrelation descriptors, information content descriptor and HOMO descriptor are very much crucial for modeling highly active chalcone compounds. Quantitative structure-activity relationships modeling of 59 set of synthesized chalcone derivatives were tested for the inhibition of mitotic G2/M phase using ridge regression and multiple linear regression methodologies. The generated model predicted that BCUT descriptors (Charge) using modified partial equalization of orbital electronegativity (MPEOE), autocorrelation descriptors, information content descriptor and HOMO descriptor are very much crucial for producing mitotic spindle inhibition of chalcone compounds.

Novel (E)-1-(pyrrole-2-yl)-3-(aryl)-2-(propen-1-one) derivatives as efficient singlet oxygen quenchers: kinetics and quantum chemical calculations

Kinetics of singlet oxygen (1O2) quenching by newly synthesized chalcone derivatives with potential antioxidant applications, and DFT/MRCI calculations.

TI-I-174, a Synthetic Chalcone Derivative, Suppresses Nitric Oxide Production in Murine Macrophages via Heme Oxygenase-1 Induction and Inhibition of AP-1.

Chalcones (1,3-diaryl-2-propen-1-ones), a flavonoid subfamily, are widely known for their anti-inflammatory properties. Propenone moiety in chalcones is known to play an important role in generating biological responses by chalcones. In the present study, we synthesized chalcone derivatives structurally modified in propenone moiety and examined inhibitory effect on nitric oxide (NO) production and its potential mechanisms. Among the chalcone derivatives used for this study, TI-I-174 (3-(2-Hydroxyphenyl)-1-(thiophen-3-yl)prop-2-en-1-one) most potently inhibited lipopolysaccharide (LPS)-stimulated nitrite production in RAW 264.7 macrophages. TI-I-174 treatment also markedly inhibited inducible nitric oxide synthase (iNOS) expression. However, TI-I-174 did not significantly affect production of IL-6, cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α), implying that TI-I-174 inhibits production of inflammatory mediators in a selective manner. Treatment of macrophages with TI-I-174 significantly inhibited transcriptional activity of activator protein-1 (AP-1) as determined by luciferase reporter gene assay, whereas nuclear factor-κB (NF-κB) activity was not affected by TI-I-1744. In addition, TI-I-174 significantly inhibited activation of c-Jun-N-Terminal kinase (JNK) without affecting ERK1/2 and p38MAPK, indicating that down-regulation of iNOS gene expression by TI-I-174 is mainly attributed by blockade of JNK/AP-1 activation. We also demonstrated that TI-I-174 treatment led to an increase in heme oxygenase-1 (HO-1) expression both at mRNA and protein level. Transfection of siRNA targeting HO-1 reversed TI-I-174-mediated inhibition of nitrite production. Taken together, these results indicate that TI-I-174 suppresses NO production in LPS-stimulated RAW 264.7 macrophages via induction of HO-1 and blockade of AP-1 activation.

Synthesis, characterization and evaluation of antioxidant activities of some novel chalcones analogues.

BackgroundChalcone, an important intermediate of flavonoid synthetic pathway, has been shown to exhibit diverse biological and pharmacological activities such as anti- cancer, antioxidant, anti-inflammatory, etc.ResultsIn this study, a novel series of chalcones fatty acid esters 5b-e and 6b-e have been synthesized via the reaction of the respective chalcones with either palmitic or stearic acid. Another related class of compounds comprising 2,3-disubstituted chalcones 7b-d and 8b(b’)-d as well as 2-amino-6-(substituted-phenyl)-4-substitutedphenyl-nicotinonitrile derivatives 9a,c,e have been also prepared by both electrophilic and Michael addition reactions, respectively, with the corresponding chalcones. The structures of all compounds are confirmed via a wide range of spectroscopic techniques including IR, 1H and 13C NMR, and mass spectra. Significantly, all synthesized compounds have been tested for their promising antioxidant activities via utilization of 1,1-biphenyl-2-picrylhydrazyl as a free radical scavenging reagent. Surprisingly, the results demonstrated that compound 5e (68.58% at C = 2 μg/ml) was more effective as an antioxidant agent than the ascorbic acid, a commonly used antioxidant. Furthermore, the role and contribution of different functional groups on the antioxidant activity of the synthesized chalcone derivatives are also probed and rationalized in terms of their electronic and structural effect.ConclusionGood activity was noted for chalcone fatty acid esters, with some members recorded higher antioxidant activity than ascorbic acid.

QSAR and docking studies on chalcone derivatives for antitubercular activity against M. tuberculosis H37Rv

In our prior studies, we reported some known antitubercular drugs (rifampicin and streptomycin) and newly synthesized chalcone derivatives (16–26) tested in vitro against Mycobacterium tuberculosis H37Rv strain. Most of the tested compounds were efficient antimycobacterial agents showing minimum inhibitory concentration values ranging from 3.5 to 30 µg mL−1. In the present work, a quantitative structure–activity relationship (QSAR) study has been performed on these active chalcone derivatives to correlate their chemical structures with their observed inhibiting activity against M. tuberculosis. A QSAR model that is able to correlate well the antitubercular activity with the chemical structures of active chalcone derivatives 16, 24, 25a, 25c, and 26 has been developed, which is potentially helpful in the design of novel and more potent antitubercular agents. The r2 and rCV2 of a newly derived QSAR model were 0.89 and 0.84, respectively. The QSAR study indicates that chemical properties, viz. heat of formation (kcal mol−1), lowest unoccupied molecular orbital energy (eV), and amine, hydroxyl, and methyl groups counts, correlate well with the activity. In silico screening results for oral bioavailability and absorption, distribution, metabolism, excretion, and toxicity compliance showed that compounds 25a, 25c, and 24 were found active similar to rifampicin and streptomycin. The docking study for the exploration of mechanism of action showed high binding affinity of active derivatives. Copyright © 2014 John Wiley &amp; Sons, Ltd.

Antiobesity, antioxidant and cytotoxicity activities of newly synthesized chalcone derivatives and their metal complexes

Four sets of rationally designed chalcones were prepared for evaluation of their antiobesity, antioxidant and cytotoxicity activities. These sets include nine oleoyl chalcones as mimics of oleoyl estrone, three monohydroxy chalcones (chalcone ligands), Schiff base-derived chalcones and four copper as well as zinc complexes. Oleoyl chalcones 4d, 4e and particularly 6a as an isosteric isomer of oleoyl estrone, were as active as Orlistat on weight loss and related metabolic parameters using male SD rats in vivo. Chalcone ligands 10a–c and Schiff base-derived chalcones 11 and 14a,b were weakly antioxidants, while, the copper and zinc complexes 15a–d were good antioxidants with zinc chelates 15b,d being more active than their copper analogues 15a,cin vitro. Compounds 10c and 14a showed good cytotoxicity activities as Doxorubicin against PC3 cancer cell line in vitro, while, the copper complex 15c showed promising activity with IC50 value of 5.95 μM. The estimated IC50 value for Doxorubicin was 8.7 μM. Chalcones 14a,b are bifunctional probes for potential investigations in cancer diagnosis and radiotherapy by complexation with Gd3+ or metal radioisotopes followed by posttranslation of Shiga toxin B-subunits that target globotriosyl ceramide expressing cancer cells.

Synthesis and Antibacterial Activity of Novel Chalcone Derivatives of Apocynin

A series of novel chalcones 1a- 1l (12 compounds) has been synthesized by using commercially available apocynin and aromatic aldehydes. The newly synthesized chalcone derivatives were screened for their antibacterial activities against gram positive and gram negative bacteria at the concentrations 10 of μg/mL with reference to the standard antibacterial drug Gentamycin. The screening results revealed that among the tested analogs, compounds having the hetero rings such as benzo[b]furan, furan and pyridine (1j,1k and 1l) in the structure exhibited excellent antibacterial activity while the compounds bearing fluorine, 2-CF3, 4-CF3 and 4-OCF3 (1f, 1g, 1h and 1i) also exhibited good to excellent activity.

Synthesis, Molecular Properties and MIC Studies of D-Ring Chalcone Derivatives of 20-Keto Pregnenolone

An efficient and simple synthesis of 17-chalconyl derivatives of pregnenolone and their antibacterial and antifungal evaluation is reported. The scheme involves the transformation of the starting pregnenolone to the corresponding Chalcone derivatives by the well-known Claisen-Schmidt reaction. Determination of Minimum inhibitory concentrations (MICs) is reported on these newly synthesized Chalcone derivatives of pregnenolone. The prediction of molecular properties is also discussed. Compounds showing lower MIC values also followedLipinski’s rule of 5. The results showed that the activity of the tested agents against each microbe varies due to structural differences between the microorganisms.

Synthesis, Characterization and Testing of Biological Activity of Some Novel Chalcones Derivatives of Coumarin

In the present communication, we herein report the synthesis of some novel derivatives of coumarin i.e. 3-((2E)-(3-(2-hydroxy-5-((aryl)diazenyl)phenyl)acryloyl)-2H-chromen-2-one (2a-2g). Various aromatic amines and salicylaldehyde in the presence of sodium nitrite and conc. HCl yielded 2-hydroxy-5-((aryl)diazenyl)benzaldehyde (1a-1g). A series of 3-((2E)-(3-(2-hydroxy-5-((aryl)diazenyl) phenyl)acryloyl)-2H-chromen-2-one were synthesized by the reaction of 2-hydroxy-5-((aryl)diazenyl) benzaldehyde and coumarin in presence of ethanol and piperidine. Different analytical techniques such as elemental analysis, IR spectra, H NMR spectra and mass spectra were used to elucidate the structures of all newly synthesized compounds (1a-1g and 2a-2g). The anti-bacterial and anti-fungal activity of newly synthesized chalcone derivatives (2a-2g) were evaluated against different bacterial and fungal stains. Some of these compounds showed promising activity against different stains.

Abstract A68: Design, synthesis, and antiproliferative evaluations of 3-phenylquinolinylchalcone derivatives against non-small cell lung cancers and breast cancers

Abstract Chalcones are natural products which have displayed a wide variety of biological activities, including anti-malarial, anti-protozoal, anti-inflammatory, immunomodulatory, nitric oxide inhibition, tyronase inhibition, and anticancer activities. Due to their abundance in plants and ease of synthesis, the chalcone class of compounds has attracted extensive studies. On the other hand, quinoline skeleton is one of the key building elements for a large number of natural and synthetic heterocycles which possess a wide variety of biological effects such as antimalarials, bactericidal, antitumor, anti-inflammatory, antiproliferative, and antiviral activities. Therefore, a series of chalcone derivatives in which an aryl moiety was replaced with quinoline nucleus have been synthesized and evaluated for their antiproliferative activities. These newly synthesized chalcone derivatives were evaluated in vitro against a panel of six cancer cell lines including three non-small cell lung cancer cells (H1299, H460, and A549), three breast cancer cells (MCF-7, MDA-MB-231, and SKBR-3), and a normal mammary epithelial cell (M10), Among them, (E)-1-(5-bromothiophen-2-yl)-3-(3-(4-methoxyphenyl)quinolin-2-yl)prop-2-en-1-one (1) was active against the growth of H1299 and SKBR-3 with IC50 values of 0.71 and 0.52 μM respectively which was more active than the positive topotecan (IC50 values of &amp;gt; 10.0 μM in each case). Compound 1 was the most active against the growth of MDA-MB-231 with an IC50 value of &amp;lt; 0.1 μM and was not cytotoxic to the normal mammary epithelial cell (M10) with an IC50 value of 9.38 μM. Mechanism studies indicated that compound 1 induced cell cycle arrest at G2/M phase followed by DNA fragmentation via activation of caspase-3, cleavage of PARP, and consequently caused the cell death. Further structural optimization is currently ongoing. Citation Format: Cherng-Chyi Tzeng, Chih-Hua Tseng, Yeh-Long Chen. Design, synthesis, and antiproliferative evaluations of 3-phenylquinolinylchalcone derivatives against non-small cell lung cancers and breast cancers. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A68.

IN VITRO SOLUBLE EPOXIDE HYDROLASE ENZYME INHIBITORY ACTIVITY OF SOME NOVEL CHALCONE DERIVATIVES

Objective Soluble epoxide hydrolase ( sEH) belongs to the α/β -hydrolase superfamily, a subclass of α/β proteins. Chalcones are chemical compounds that show hopeful obliging efficacy in controlling numerous diseases. The main objective of the study is to evaluate the sEH inhibitory activity of some synthesized chalcone derivatives and identification of its mode of inhibition. Methods Four different chalcone derivatives (PC-1 to PC-4) were selected for synthesis by Claisen-Schmidt method. The in vitro sEH inhibitory activity was performed for the synthesized compounds by fluorimetric assay. The percentage of sEH activity and IC 50 values were calculated for the synthesized compounds. Dissociation constant were determined by following the method described by Lineweaver-Burks plot. Results and Conclusions The IC 50 value obtained for PC-1, PC-2, PC-3, and PC-4 were found to be 0.8213 µg/mL, 2.64 µg/mL, 0.2490 µg/mL and 0.5238 µg/mL respectively. The order of potency (IC 50 ) of the chalcone and chalcone oxide in sEH inhibition assay was PC-3 > PC-4 > PC-1 >PC-2. All the compounds (PC-1, PC-2, PC-3) showed mixed type of inhibition except PC-4 which showed non-competitive type of inhibition. Further in vivo studies are to be carried out for these compounds to confirm their activity and explore the mechanism by which these compounds act and rationalize their use.

A comparative study on synthesis of some novel α,β-unsaturated carbonyl derivatives and their antioxidant potential

Free radicals are constantly formed in human system either as accidental products during metabolism or deliberately during the process of phagocytosis or due to environmental pollutants, ionizing radiations, ozone, heavy metal poisoning, etc. It is found from literature survey that chalcones (α,β-unsaturated carbonyl derivatives) exhibit great antioxidant activity. Hence, the synthesis of some new chalcone derivatives was undertaken and were synthesized by two methods namely, conventional and microwave irradiation methods. The synthesized chalcone derivatives were tested for their in vitro antioxidant activity by using NBT-superoxide free-radical scavenging activity and DPPH radical scavenging activity. The potency of the chalcone derivatives was estimated by IC 50 values and they have shown promising antioxidant activity. Among all the chalcones synthesized, derivative 3e showed maximum superoxide inhibition as per NBT method and all the derivatives have shown different percentage inhibitions at different concentrations as per DPPH method. The compounds were characterized by 1 H NMR and IR spectral analysis.