Flavone Analogues Research Articles

An insight into the role of ESIPT/TICT-based antioxidant flavone analogues in fluoro-probing diabetes-induced viscosity changes: a unified experimental and theoretical endeavour.

Potent antioxidants, like 3-hydroxy flavones, attracted considerable attention due to their excited state intramolecular proton transfer (ESIPT)-based fluorescence behaviour. This article is an interesting demonstration of a series of synthetic 3-hydroxy flavone analogues having high antioxidant activity as molecular rotor-like viscosity probes. Among these flavone analogues, 4'-N,N-dimethylamino-3-hydroxy flavone (3) is the most potent one, showing the twisted intramolecular charge transfer (TICT)-dependent fluoroprobing activity toward the blood viscosity changes associated with diabetes and free fatty acids (FFA)-induced nuclear viscosity changes of MIN6 cells. The TICT dynamics of (3), which instigates its viscosity probing activity, was comprehended with the help of DFT-based computational studies. Abnormal cellular viscosity changes are the pathological traits for various diseases, and non-toxic flavone-based viscosity probes can be useful for diagnosing such pathological conditions.

Exploring the anticancer potential of fluoro flavone analogues: insights from molecular docking and dynamics studies with Aurora Kinase B.

Exploring the anticancer potential of fluoro flavone analogues: insights from molecular docking and dynamics studies with Aurora Kinase B.

Exploring the effectiveness of flavone derivatives for treating liver diseases: Utilizing DFT, molecular docking, and molecular dynamics techniques

In exploring nature's potential in addressing liver-related conditions, this study investigates the therapeutic capabilities of flavonoids. Utilizing in silico methodologies, we focus on flavone and its analogs (1–14) to assess their therapeutic potential in treating liver diseases. Molecular change calculations using density functional theory (DFT) were conducted on these compounds, accompanied by an evaluation of each analog's physiochemical and biochemical properties. The study further assesses these flavonoids' binding effectiveness and locations through molecular docking studies against six target proteins associated with human cancer. Tropoflavin and taxifolin served as reference drugs. The structurally modified flavone analogs (1–14) displayed a broad range of binding affinities, ranging from -7.0 to -9.4 kcal mol⁻¹, surpassing the reference drugs. Notably, flavonoid (7) exhibited significantly higher binding affinities with proteins Nrf2 (PDB:1 × 2 J) and DCK (PDB:1 × 2 J) (-9.4 and -8.1 kcal mol⁻¹) compared to tropoflavin (-9.3 and -8.0 kcal mol⁻¹) and taxifolin (-9.4 and -7.1 kcal mol⁻¹), respectively. Molecular dynamics (MD) simulations revealed that the docked complexes had a root mean square deviation (RMSD) value ranging from 0.05 to 0.2 nm and a root mean square fluctuation (RMSF) value between 0.35 and 1.3 nm during perturbation. The study concludes that 5,7-dihydroxyflavone (7) shows substantial promise as a potential therapeutic agent for liver-related conditions. However, further validation through in vitro and in vivo studies is necessary.Key insights from this study include:•Screening of flavanols and their derivatives to determine pharmacological and bioactive properties using ADMET, molinspiration, and pass prediction analysis.•Docking of shortlisted flavone derivatives with proteins having essential functions.•Analysis of the best protein-flavonoid docked complexes using molecular dynamics simulation to determine the flavonoid's efficiency and stability within a system.

Flavones and Related Compounds: Synthesis and Biological Activity.

This review focuses on the synthesis and biological activity of flavones and their related flavonoidic compounds, namely flavonols and aurones. Among the biological activities of natural and synthetic flavones and aurones, their anticancer, antioxidant, and antimicrobial properties are highlighted and detailed in this review. Starting from the structures of natural flavones acting on multiple anticancer targets (myricetin, genkwanin, and other structurally related compounds), new flavone analogs were recently designed and evaluated for their anticancer activity. The most representative compounds and their anticancer activity are summarized in this review. Natural flavones recognized for their antimicrobial properties (baicalein, luteolin, quercetol, apigenin, kaempferol, tricin) have been recently derivatized or structurally modulated by chemical synthetic methods in order to obtain new effective antimicrobial flavonoidic derivatives with improved biological properties. The most promising antimicrobial agents are systematically highlighted in this review. The most applied method for the synthesis of flavones and aurones is based on the oxidative cyclization of o-hydroxychalcones. Depending on the reaction conditions and the structure of the precursor, in some cases, several cyclization products result simultaneously: flavones, flavanones, flavonols, and aurones. Based on the literature data and the results obtained by our research group, our aim is to highlight the most promising methods for the synthesis of flavones, as well as the synthetic routes for the other structurally related cyclization products, such as hydroxyflavones and aurones, while considering that, in practice, it is difficult to predict which is the main or exclusive cyclization product of o-hydroxychalcones under certain reaction conditions.

<em>In silico</em> pharmacokinetic and toxicological study of Flavone analogues

Flavone analogs are natural compounds of the flavonoid class that have a wide range of biological activities. The present study aimed to predict, with the aid of in silico methodologies, the oral bioavailability and pharmacokinetic and toxicological analyzes for three flavone analogues (apigenin, chrysin and luteonlin). The study revealed that the analogues have good oral availability, favorable pharmacokinetic and toxicological parameters. The Virtual Screening performed to predict oral bioavailability revealed that all analogues did not violate Lipinski's Rule. The in silico pharmacokinetic study revealed that all analogues have high intestinal absorption, do not cross the blood-brain barrier, are permeable by Caco-2 cells and do not inhibit P-glycoprotein. The in silico ADME study showed that all analogues inhibit the enzymes of the cytochrome P450 complex (CYP4501A2, CYP4502C9, CYP4502C19, CYP4503A4) and not only the CYP4502D6 enzyme. The in silico Toxicology study indicated that the analogues do not show toxicity by the AMES Test and are not carcinogenic. Apigenin and chrysin have low toxicity, while luteolin has moderate toxicity.

Design, synthesis, in vitro, in silico, and SAR studies of flavone analogs towards anti-dengue activity

Flavone has recently been proved as a promising scaffold for the development of a novel drug against dengue fever, one of the major health threats globally. However, the structure–activity relationship study of flavones on the anti-dengue activity remains mostly limited to the natural-occuring analogs. Herein, 27 flavone analogs were successfully synthesized, of which 5 analogs (5e, 5h, 5o, 5q, and 5r) were novel. In total, 33 analogs bearing a diverse range of substituents were evaluated for their efficacy against DENV2-infected LLC/MK2 cells. The introduction of electron-withdrawing groups on ring B such as Br (5m) or NO2 (5n and 5q) enhanced the activity significantly. In particular, the tri-ester 5d and di-ester 5e exhibited low toxicity against normal cell, and exceptional DENV2 inhibition with the EC50 as low as 70 and 68 nM, respectively, which is over 300-fold more active compared to the original baicalein reference. The viral targets for these potent flavone analogs were predicted to be NS5 MTase and NS5 RdRp, as suggested by the likelihood ratios from the molecular docking study. The great binding interaction energy of 8-bromobaicalein (5f) confirms the anti-dengue activity at atomistic level. The physicochemical property of all the synthetic flavone analogs in this study were predicted to be within the acceptable range. Moreover, the QSAR model showed the strong correlation between the anti-dengue activity and the selected molecular descriptors. This study emphasizes the great potential of flavone as a core structure for further development as a novel anti-dengue agent in the future.

Synthesis and evaluation of 7-(3-aminopropyloxy)-substituted flavone analogue as a topoisomerase IIα catalytic inhibitor and its sensitizing effect to enzalutamide in castration-resistant prostate cancer cells

Prostate cancer patients primarily receive androgen receptor (AR)-targeted drugs as a primary treatment option because prostate cancer is associated with highly activated AR signaling. AR amplification made prostate cancer cells viable under treatment of AR-targeted therapy, leading to castration resistance. AR amplification was more common in enzalutamide-resistant patients. As a strategy to overcome castration resistance and to improve the efficacy of enzalutamide, second-generation nonsteroidal antiandrogen drugs for castration-resistant prostate cancer (CRPC) including topoisomerase II (topo II) poisons such as etoposide and mitoxantrone, have been administered in combination with enzalutamide. In the present study, it was confirmed that amplification of topo IIα, but not I and IIβ, was directly and proportionally associated with poor clinical outcome of Prostate cancer. Among a novel series of newly designed and synthesized 7-(3-aminopropyloxy)-substituted flavone analogues, compound 6, the most potent derivative, was further characterized and identified as a topo IIα catalytic inhibitor that intercalates into DNA and binds to the DNA minor groove with better efficacy and less genotoxicity than etoposide, a topo II poison. Compound 6 showed remarkable efficacy in inhibiting AR-negative CRPC cell growth and sensitizing activity to enzalutamide in AR-positive CRPC cells, thus confirming the potential of topo IIα catalytic inhibitor to overcome resistance to androgen deprivation therapy.

Identification of a novel nitroflavone-based scaffold for designing mutant-selective EGFR tyrosine kinase inhibitors targeting T790M and C797S resistance in advanced NSCLC

The inhibition of the Epidermal Growth Factor (EGFR) represents one of the most promising strategies in non-small cell lung cancer (NSCLC) therapy. The recently identified C797S mutation causes resistance of EGFRL858R/T790M against osimertinib, the latest approved third generation EGFR inhibitor. The identification of small molecules capable of selectively inhibiting the T790M mutations also in the late-onset C797S mutation is a desirable strategy and novel chemical structures might provide new insight in the overcoming resistance mechanisms. Here we report the identification of a novel mutant-selective privileged molecular core; guided by a structure-based drug design, a flavone skeleton has been rationally modified, and a virtual library generated. Reversible EGFR inhibitors targeting both L858R/T790M and L858R/T790M/C797S mutations with a higher affinity with respect to the wild type one are discovered via a three-track virtual screening. Selected hits were synthesized and tested in an activity-based enzyme assay against wild-type EGFR, L858R/T790M, as well as L858R/T790M/C797S. The results showed that a nitroflavone-based compound inhibits the phosphorylation of EGFR mutants at low-micromolar concentration showing selectivity over the wild type ones. Structurally similar flavone analogues have been synthesized and the following inhibition assays underlied the importance of both the presence and position of the nitrophenoxy moiety.

FLAVONES AND THEIR DERIVATIVES: SYNTHETIC AND PHARMACOLOGICAL IMPORTANCE

Flavones (from the Latin flavus, which means “yellow”) are a kind of flavonoid with a backbone of 2-phenylchromen-4-one. Flavones, one of the most important classes of plant secondary metabolites, are well-known for their anti-cancer, anti-inflammatory, anti-microbial, antioxidant, anti-osteoporatic, anti-diabetic, anti-estrogenic, anti-allergic, and metal chelating properties. These family compounds have been intensively studied synthetically due to their wide spectrum of biological actions, and more than 4000 chemically distinct flavonoids have been identified from plants. However, new advances in synthetic chemistry have resulted in the production of a number of therapeutically important derivatives. This article summarizes the synthesis of flavones, their derivatives, and other flavone analogues which have the potential for treating a range of illnesses and ailments.

Structure-based identification and pathway elucidation of flavonoids in Camptotheca acuminate

Flavonoid metabolism in Camptotheca acuminate remained an untapped area for years. A tandem MS approach was used and focused on the mining and characterizing of flavonoids in mature C. acuminate. Fifteen new flavonoids and forty-three known flavonoids, including fifteen flavone analogs, sixteen flavonol analogs, seven flavanone analogs, six chalcone analogs, four xanthone analogs, ten flavane analogs were mined and identified based on their MS/MS fragments. Fifty-three of them were firstly characterized in C. acuminate. Eight biosynthetic precursors for these flavonoids were also identified. We constructed a specific metabolic map for flavonoids according to their relative contents in the flowers, fruits, stems, and leaves of C. acuminate. Furthermore, the most probable genes involved in chalcone biosynthesis, flavonoid hydroxylation, methylation, and glycosylation were further mined and fished in the gene reservoir of C. acuminate according to their conserved domains and co-expression analysis. These findings enable us to acquire a better understanding of versatile flavonoid metabolism in C. acuminate.

Bioactivity evaluation of synthesized flavone analogs

Flavonoids are natural phenolic compounds found in dietary sources such as plants, fruits, and vegetables. They have a wide range of biological activities including cytostatic and anti-inflammatory effects. In this research, we synthesized flavone derivatives via the introduction of various aryl functional groups. Furthermore, we combined flavones with gallic acid derivatives. The synthesized compounds were tested against cervical (HeLa) and colon cancer cells (CaCo-2). Moreover, the synthesized compounds were evaluated for their antioxidant and anti-inflammatory activities using DPPH and COX inhibition tests, respectively. The success of the synthesis of our target compounds was confirmed using IR and NMR. Compound 3 potently inhibited the proliferation of CaCo-2 cells (IC50 = 2.42 µg/mL). Meanwhile, compound 4 exhibited antioxidant activity (IC50 = 3.53 ± 0.1 µg/mL). Moreover, compound 4 selectively inhibited COX-2 with an IC50 = 6.02 ± 0.33 µg/mL; it was approximately 6-fold more selective for COX-2 than for COX-1 enzymes. In conclusion, the results strongly indicate that the chemical modification of flavones enhances their bioactivity. Further investigation of in vivo anti-inflammatory and anticancer evaluation of active compounds is required to prove both safety and efficacy.

Synthesis, Structural Characterization, Catalytic, Biological and α-Glucosidase Inhibitory Studies of Metal Complexes with Flavone Derivatives

Heterocyclic compounds, in particular oxygen-containing heterocyclic compounds, are of special interest to medicinal chemists because of their unusual biological properties. In the present study, the highly conjugated nitrogen heterocyclic scaffold comprised of flavone derivative with metal acetates to form metal chelates of the type [MIIL(OAc)2], flavone analogues (L); M=Co2+, Zn2+, Cu2+ and Ni2+. The above title compounds were characterized using composition analysis o fCHN and spectroscopic techniques. Based on spectroscopic and analytical measurements confirmed that square planar arrangements for the Co2+, Zn2+, Cu2+ and Ni2+ complexes. Antimicrobial efficacy of prepared complexes were assessed against A.flavus, A.niger, B.subtilis, E. coli, C. albicans and S.aureus. The anti-mycobacterial (H37Rv) efficacy of flavone analogues and its complexes were screened using MABA approach and compared with standard. The acetylcholinesterase (AChE) inhibitory effect of the ligand was examined to find out the therapeutic efficiency of compound in the treatment of neurodegenerative disorders. The synthesized ligand exhibited selective inhibition (AChE & BuChe) values (IC50:0.20(flavone analogue), 2.41 (Rivastigmine) and 3.01 µM (Galantamine), respectively. Further, the in vitro ant-inflammatory efficiency of metal chelates were performed with the help of egg albumin method. The α-glucosidase inhibition activity was also carried out for the prepared metal complexes.

Rutin and flavone analogs as prospective SARS-CoV-2 main protease inhibitors: In silico drug discovery study

Coronavirus disease 2019 (COVID-19) is a new pandemic characterized by quick spreading and illness of the respiratory system. To date, there is no specific therapy for Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Flavonoids, especially rutin, have attracted considerable interest as a prospective SARS-CoV-2 main protease (Mpro) inhibitor. In this study, a database containing 2017 flavone analogs was prepared and screened against SARS-CoV-2 Mpro using the molecular docking technique. According to the results, 371 flavone analogs exhibited good potency towards Mpro with docking scores less than −9.0 kcal/mol. Molecular dynamics (MD) simulations, followed by molecular mechanics-generalized Born surface area (MM/GBSA) binding energy calculations, were performed for the top potent analogs in complex with Mpro. Compared to rutin, PubChem-129-716-607 and PubChem-885-071-27 showed better binding affinities against SARS-CoV-2 Mpro over 150 ns MD course with ΔGbinding values of −69.0 and −68.1 kcal/mol, respectively. Structural and energetic analyses demonstrated high stability of the identified analogs inside the SARS-CoV-2 Mpro active site over 150 ns MD simulations. The oral bioavailabilities of probable SARS-CoV-2 Mpro inhibitors were underpinned using drug-likeness parameters. A comparison of the binding affinities demonstrated that the MM/GBSA binding energies of the identified flavone analogs were approximately three and two times less than those of lopinavir and baicalein, respectively. In conclusion, PubChem-129-716-607 and PubChem-885-071-27 are promising anti-COVID-19 drug candidates that warrant further clinical investigations.

Unfolding the Role of a Flavone-Based Fluorescent Antioxidant towards the Misfolding of Amyloid Proteins: An Endeavour to Probe Amyloid Aggregation.

4'-N,N-Dimethylamino-3-hydroxyflavone (DMAHF), a synthetic fluorescent flavone analogue with potent antioxidant activity, was explored as a molecular rotor-like fluoroprobe for amyloid aggregations, a causative factor in Alzheimer's disease, Parkinson's disease, type-2 diabetes, etc. During its interactions with (human) insulin amyloid aggregation (IAA), its microenvironment was changed. This instigated a drastic change in its excited-state intramolecular proton transfer-based dual emission behavior, which was tracked to monitor its amyloid probing activity. Thus, the amyloid probing potential of DMAHF was originated from its interactions with IAA, which were studied by various spectroscopic techniques and molecular docking and quantum-mechanical calculations. Morphological changes of the IAA in the presence of DMAHF were studied by scanning electron microscopy. DMAHF also probed efficiently the islet amyloid polypeptide deposition in the pancreatic β-cells of diabetic mice. DMAHF showed significant sensitivity and specificity towards amyloid aggregation without having any complexity in its photophysical behavior. This indicates its potential as an ideal bio-friendly and cost-effective fluoroprobe for amyloid proteins.

Molecular docking studies of some flavone analogues as α-Glucosidase inhibitors

Molecular docking studies of some flavone analogues as α-Glucosidase inhibitors

Preparation and in vitro antioxidant activity of some novel flavone analogues bearing piperazine moiety

BackgroundA series of eight new flavone derivatives containing a piperazine chain with different substitution were synthesized and their structures were determined. MethodsTheir antiradical and antioxidant activities were evaluated using superoxide anion radical, hydroxyl radical, 2,2-diphenyl-1-picrylhydrazyl radical, 2,2′-azino-di(3-ethylbenzthiazoline sulphonate) radical cation (ABTS+) scavenging (as measure total antioxidant status TAS), ferric reducing antioxidant power (TAC), and hydrogen peroxide decomposition. The antioxidant activities of the synthesized compounds were compared with standard antioxidants trolox, ascorbic acid, butylated hydroxytoluene (BHT) as positive controls, reference antibiotics (doxycycline, dicloxacillin), and medicinal plants (Menthae piperita, Cistus incanus). Chemiluminescence, spectrophotometry, electron spin resonance (ESR) spectroscopy in conjunction with 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as the spin trap were the measurement techniques. ResultsThe results show that the synthesized compounds exhibit weak, albeit a wide spectrum of antiradical and antioxidant activities. The TAS values were measured as trolox equivalents, ranging from 209.6 ± 6.1 to 391.1 ± 8.2 µM TE/g; the TAC values were in ranges from 10.8 ± 0.5 to 49.5 ± 0.5 µM TE/g being higher than that of dicloxacillin (241.0 ± 16.5 and 9.73 ± 0.8 µM TE/g, respectively), but lower than ascorbic acid, BHT, doxycycline, and medicinal plants. Best antioxidant activities were found for the piperazinyl analogues with methoxy group on phenyl piperazine ring. ConclusionWe suggest that the synthesized compounds may be used as lead molecules for optimization of molecular structure to maximize the antioxidant potency.

Flavonoids as alpha-glucosidase inhibitors: mechanistic approaches merged with enzyme kinetics and molecular modelling

Diabetes mellitus is a major, global public health problem. α-Glucosidase inhibitors are one of the most widely used classes of oral antidiabetics. In addition to other pharmaceutical benefits, flavonoids are known as potent α-glucosidase inhibitors. In the last two decades, the latter property of flavonoids has attracted a great interest. In the current review, the literature on flavonoids as inhibitors of α-glucosidase enzyme, their mechanism of action along with in silico studies and structure–activity relationships is discussed. The main outcomes show that a double bond between C-2 and C-3, and free hydroxyl groups at C-3 and C-4′ are crucial. Whereas sugar substitution at any position on the aglycon reduced the inhibitory effect, a phenolic group like gallic acid, coumaric acid, etc. substituted at different positions of sugar units increased it. Hydroxylation of flavonoids generally enhanced the effect due to possible electrostatic interactions with the enzyme, making flavonols stronger inhibitors than their flavone analogues. Hydroxyl groups at C-3, C-7, ring B, and the carbonyl oxygen at C-4 are considered to be key modifications to enhance binding through hydrogen bonds. With this overview we intend to motivate and challenge researchers to design novel flavonoids a find new hits.

3D-QSAR, Docking, ADME/Tox studies on Flavone analogs reveal anticancer activity through Tankyrase inhibition

Flavones are known as an inhibitor of tankyrase, a potential drug target of cancer. We here expedited the use of different computational approaches and presented a fast, easy, cost-effective and high throughput screening method to identify flavones analogs as potential tankyrase inhibitors. For this, we developed a field point based (3D-QSAR) quantitative structure-activity relationship model. The developed model showed acceptable predictive and descriptive capability as represented by standard statistical parameters r2 (0.89) and q2 (0.67). This model may help to explain SAR data and illustrated the key descriptors which were firmly related with the anticancer activity. Using the QSAR model a dataset of 8000 flavonoids were evaluated to classify the bioactivity, which resulted in the identification of 1480 compounds with the IC50 value of less than 5 µM. Further, these compounds were scrutinized through molecular docking and ADMET risk assessment. Total of 25 compounds identified which further analyzed for drug-likeness, oral bioavailability, synthetic accessibility, lead-likeness, and alerts for PAINS & Brenk. Besides, metabolites of screened compounds were also analyzed for pharmacokinetics compliance. Finally, compounds F2, F3, F8, F11, F13, F20, F21 and F25 with predicted activity (IC50) of 1.59, 1, 0.62, 0.79, 3.98, 0.79, 0.63 and 0.64, respectively were find as top hit leads. This study is offering the first example of a computationally-driven tool for prioritization and discovery of novel flavone scaffold for tankyrase receptor affinity with high therapeutic windows.

Antioxidant flavone functionalized fluorescent and biocompatible metal nanoparticles: Exploring their efficacy as cell imaging agents

A synthetic fluorescent antioxidant flavone analog, 4′-N,N-dimethylamino-3-hydroxy flavone (DMAHF) was successfully explored as the green multifunctional agents for the synthesis of stable monometallic Au and Ag and bimetallic Au/Ag alloy nanoparticles with tailor-made morphologies. The synthesis of these nanoparticles were done in three types of surfactants e.g. sodium dodecyl sulfate (SDS), polyvinylpyrrolidone (PVP) and cetyltrimethylammonium bromide (CTAB). In addition to DMAHF itself, these surfactants have a pronounced effect on the morphology and surface chemistry of these nanoparticles. DMAHF has high fluorescent activity and it is a potent antioxidant. It imparted its characteristic fluorescence and antioxidant activities to these nanoparticles. At the same time these fluorescent and antioxidant nanoparticles were biocompatible as evidenced from their cytotoxicity assays on normal lung cell (L132). These nanoparticles also showed selective colorimetric sensing activity towards thiol containing amino acids, like cysteine and glutathione. The fluorescence activity of these biocompatible nanoparticles was further utilized for the cell imaging process. In future these nanoparticles can be used as the fluorescent probes for biomolecules in living systems.

Synthesis, Biological Evaluation and Docking Studies of Chalcone and Flavone Analogs as Antioxidants and Acetylcholinesterase Inhibitors

Several oxidative processes are related to a wide range of human chronic and degenerative diseases, like Alzheimer’s disease, which also has been related to cholinergic processes. Therefore, search for new or improved antioxidant molecules with acetylcholinesterase activity is essential to offer alternative chemotherapeutic agents to support current drug therapies. A series of chalcone (2a–2k) and flavone (3a–3k) analogs were synthesized, characterized, and evaluated as acetylcholinesterase (AChE) inhibitors, and antioxidant agents using 1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2-2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS•), and β-carotene/linoleic acid bleaching assay. Compounds more active were 3j and 2k in DPPH with EC50 of 1 × 10−8 and 5.4 × 10−3 μg/mL, respectively; 2g and 3i in ABTS (1.14 × 10−2 and 1.9 × 10−3 μg/mL); 2e, 2f, 3f, 2j, and 3j exceeded the α-tocopherol control in the β-carotene assay (98–99% of antioxidant activity). At acetylcholinesterase inhibition assay, flavones were more active than chalcones; the best results were compounds 2d and 3d (IC50 21.5 and 26.8 µg/mL, respectively), suggesting that the presence of the nitro group enhances the inhibitory activity. The docking of these two structures were made to understand their interactions with the AChE receptor. Although further in vivo testing must be performed, our results represent an important step towards the identification of improved antioxidants and acetylcholinesterase inhibitors.