Compounds 4g Research Articles

New Pyrazolo-Benzimidazole Mannich Bases with Antimicrobial and Antibiofilm Activities.

A new series of pyrazolo-benzimidazole hybrid Mannich bases were synthesized, characterized by 1H-NMR, 13C-NMR, IR, UV-Vis, MS, and elemental analysis. In vitro cytotoxicity of the new compounds studied on fibroblast cells showed that the newly synthesized pyrazolo-benzimidazole hybrid derivatives were noncytotoxic until the concentration of 1 μM and two compounds presented a high degree of biocompatibility. The antibacterial and antibiofilm activity of the newly synthesized compounds was assayed on Gram-positive Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, and Gram-negative Pseudomonas aeruginosa ATCC27853, Escherichia coli ATCC25922 strains. All synthesized compounds 5a–g are more active against all three tested bacterial strains Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, and Escherichia coli ATCC25922 than reference drugs (Metronidazole, Nitrofurantoin), with the exception of compounds 5d and 5g, which are less active compared to Nitrofurantoin, and all synthesized compounds 5a–g are more active against Pseudomonas aeruginosa ATCC27853 compared to reference drugs (Metronidazole, Nitrofurantoin). Compound 5f showed the best activity against Staphylococcus aureus ATCC 25923, with a MIC of 150 μg/mL and has also inhibited the biofilm formed by all the bacterial strains, having an MBIC of 310 µg/mL compared to the reference drugs (Metronidazole, Nitrofurantoin).

Design, Synthesis and Bioevaluation of Highly Functionalized 1,2,3-Triazole-Guanidine Conjugates as Anti-Inflammatory and Antioxidant Agents

In search of new biologically potent molecules a small focused library of new guanidine-1,2,3-triazole hybrid derivatives were synthesized via Organocatalytic enolate- mediated azide-carbonyl [3 + 2] cycloaddition yielding a highly functionalized triazole core structure. The synthesis of all the derivatives were confirmed by spectral analysis 1H NMR, 13C NMR and MS. The new guanidine-1,2,3-triazole conjugates were found to exhibit promising anti-inflammatory and antioxidant activity. The anti-inflammatory activity screened by membrane stabilization method summarizes the four potential conjugates 5c, 5f, 5h and 5g to be potent in comparison with standard drug Diclofenac sodium (DFS). The conjugates were also assessed for antioxidant potential by DPPH method. Among all the synthesized compounds, the compounds 5d, 5f, 5g and 5h exhibited potent antioxidant activity. Molecular docking study was performed to gain insight into the putative binding mode and binding strength of these compounds with the target enzyme Cyclo-oxygenase (COX-2) enzyme. The in vitro and in silico studies together with simpler designing and synthesis strategy via Organocatalytic enolate- mediated azide-carbonyl [3 + 2] cycloaddition followed by a two-component reaction with guanidine in basic conditions rationalize guanidine-1,2,3-triazole hybrid derivatives as easily assessable novel therapeutic agents.

Development of new donepezil analogs: synthesis, biological screening and in silico study rational

Fifteen new benzothiophene-based compounds were designed, synthesized, and evaluated as potential anti-Alzheimer agents. Most of the synthesized compounds exhibited remarkable AChE inhibitory activity and effectively inhibited self-mediated β-amyloid protein in vitro. Compound 3g (IC50 = 72.488 ± 3.69 μM) showed a significant β-amyloid inhibitory effect exceeding that of donepezil (IC50 = 87.414 ± 4.46 μM). Furthermore, compound 3j (IC50 = 0.498 ± 0.02 μM) showed the best inhibitory activity comparable to that of donepezil (IC50 = 0.404 ± 0.03 μM). The in vivo evaluation of the promising compounds (3g and 3j) confirmed a significant memory improvement in scopolamine-induced memory impairment model in mice. The molecular docking simulation of compounds 3g and 3j in Torpedo californica-AChE (TcAChE) active site showed a good agreement with the obtained screening results. The in silico ADMET and other physicochemical parameters were also reported.

Oleanane-Type Triterpene Conjugates with 1H-1,2,3-Triazole Possessing of Fungicidal Activity.

The triazole pesticide is an organic nitrogen-containing heterocyclic compound with a 1,2,3-Triazole ring. In order to develop a potential glucosamine-6-phosphate synthase (GlmS) inhibitor bactericide, 18 triazole-derivative compounds were synthesized efficiently. In addition, these compounds have not been reported in the literature. The structure was confirmed by high-resolution mass spectrometry (HRMS), H NMR and C NMR. The potential use of the most promising derivatives has been investigated by testing their antifungal activity and enzyme inhibitory activity, revealing inhibitory activities in the low micromolar range. Among them, the antifungal effects of compounds 1e, 1f, 1g, 2e, 2f, and 2g on Sclerotinia sclerotiorum were particularly significant, all of which were above 83%. These compounds will be further investigated as potential antifungal lead compounds. Their structure–activity relationships are discussed based on the effects of substituted phenyl groups on compounds.

Synthesis and evaluation of novel almazole D analogs as anticancer agents

Novel almazole D-amide conjugates, esters, and N-alkylated analogs were synthesized and investigated for their anticancer activity against seven cancer cell lines. Among the series, compounds 5g and 5m showed significant anticancer activities against multiple cell lines with moderate selectivity indices. Compound 5g had IC50 values of 5.86 ± 0.31, 9.94 ± 0.06, 12.74 ± 0.12, and 9.40 ± 0.03 μM against the B16-F10, DU145, HeLa, and LC-540 cell lines, respectively, while compound 5m showed IC50 values of 6.35 ± 0.09, 9.17 ± 0.11, 9.00 ± 0.011, 19.65 ± 0.63, 8.13 ± 0.04, and 11.56 ± 0.01 μM against B16-F10, DU145, HeLa, HepG2, LC-540, and SK-BR-3 cells, respectively. Compared to almazole D, which only showed significant activity against B16-F10 cells (IC50 = 9.05 ± 0.008 μM), the synthesized analogs showed improved anticancer activity against multiple cell lines. The kinase inhibition assay coupled with the docking studies revealed that epidermal growth factor receptor(EGFR) kinase inhibition via interaction with amino acid residue T790 on the EGFR is one of the possible mechanisms by which 5g exerts its anticancer potential. The ADMET prediction and drug-likeness of the analogs project the synthesized analogs as promising agents, which can be further developed for application in cancer therapy.

Synthesis and Biological Evaluation of Coumarin Carboxamides as Selective and Potent Inhibitors of Carbonic Anhydrases IX and XII

Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the reversible hydration of carbon dioxide to bicarbonate and proton. Inhibition of isoforms IX and XII could aid in the amelioration of cancer. A series of coumarin carboxamides (6a-j) were synthesized and were assayed against hCA isoforms I, II, IX, and XII. Thin Layer Chromatography (TLC) analysis was done by utilizing Merck silica gel 60 F254 aluminum plates. Stuart Digital Melting Point Apparatus (SMP 30) was used in determining the melting points of the compounds, which are uncorrected. High Resolution Mass Spectra (HRMS) were determined by Agilent QTOF mass spectrometer 6540 series instrument and were performed using ESI techniques at 70eV. All the compounds selectively inhibited isoforms IX and XII as against hCAs I and II. Compounds 6a-e exhibited the best inhibitory profiles against hCA IX (Ki < 25 nM). The isoform hCA XII was effectively inhibited by all compounds showing the Ki values less than 65 nM. The Compounds 6a, 6b, 6g, 6h, and 6j exhibited Ki values less than 10 nM. The binding interactions of the most potent compounds, 6a and 6b, were investigated through docking studies with hCAs IX and XII. These compounds may be utilized as useful starting points for the design and development of selective and potent hCA IX and XII inhibitors.

Design, Synthesis, Anti-microbial and Molecular Docking Studies of Novel 5-Pyrazyl-2-Sulfanyl-1, 3, 4-Oxadiazole Derivatives.

Chemical modification of Oxadiazole may lead to a potent therapeutic agent. A series of novel 5-pyrazyl-2-sulfanyl-1, 3, 4-oxadiazole derivatives (5ag) have been synthesised utilising pyrazinoic acid as a precursor. The new oxadiazole compounds were docked against potential targets and evaluated for antibacterial and antitubercular activity. The 5-pyrazyl-2-substituted sulfanyl-1, 3,4-oxadiazole derivatives (5a-g) were synthesized from the crucial intermediate 2-sulfanyl-5-pyrazyl-1, 3,4-oxadiazole (4), which was prepared by treating the 2-pyrazyl hydrazide with CS2 and pyridine. IR, 1HNMR, 13C, MS and elemental analyses were used to confirm the chemical structures. Antimicrobial activity was determined for each synthesized compound. Additionally, compounds were evaluated for antitubercular activity against the Mycobacterium Tuberculosis H37Rv strain. Compounds 5c, 5g, and 5a had a favourable antibacterial profile, while 5c and 5g (MIC = 25 g/ml) demonstrated potential antitubercular activity when compared to the other produced compounds. Molecular docking experiments using V-Life Science MDS 4.6 supplemented the biological data. Each compound has been tested for antibacterial and antitubercular action against a variety of microorganism strains and exhibits considerable activity. Additionally, molecular docking analysis confirmed the experimental results by describing improved interaction patterns.

Cinnamamide-chalcone derivatives as CDK2 inhibitors: synthesis, pharmacological evaluation, and molecular modelling study

Thirteen novel cinnamamide-chalcone derivatives were synthesized and tested for their antiproliferative activity against MCF-7, K562, U-373MG, and HT-29 cell lines using SRB assay. Eight compounds were tested for the in vitro CDK2 inhibition. Compounds 2g, 2h, 2k, and 2l were found to have IC50 < 10 µM for CDK2. These four compounds were evaluated on EGFR kinase and found to be two times more selective for CDK2. Eight compounds were docked into the CDK2 using Glide software. The docking studies revealed that Lys33 and Leu83 were crucial for binding to CDK2 and docking scores correlate well with the IC50 values. We docked these compounds in EGFR, and they had lower docking scores. Most compounds interacted only with Met769 in EGFR. Molecular dynamic simulation was performed using Desmond software, and the interactions for compounds 2k and 2l with CDK2 were stable.

Design, synthesis and mechanism of action of novel 1,9-disubstituted β-carboline derivatives as antitumor agents

A range of novel 1,9-disubstituted β-carboline derivatives was designed, synthesized and evaluated as potential anticancer agents. The preliminary study suggested that compounds 6a, 6b, 6c, 6d, 6e, 6f, 6g, and 6h tested in this study exerted potent antiproliferative effects on ten selected human tumor cell lines, with compound 6e being the most effective antiproliferative agent against the BGC-823, A375 and HT-29 cell lines, with IC50 values of 23.9, 9.3, and 3.6 µM, respectively. In addition, the antitumor capability of compound 6e was also evaluated in vivo, which demonstrated that compound 6e distinctly inhibited colorectal tumor growth in syngeneic BALB/c mice. Further research into the fundamental mechanism revealed that compound 6e inhibited colorectal cancer growth through the ATG5 (autophagy-related-5)/ATG7 (autophagy-related-7)-dependent autophagy pathway. This research can contribute to further clinical application of β-carboline derivatives as new antitumor drugs.

Design and synthesis of novel benzimidazole linked thiazole derivatives as promising inhibitors of drug-resistant tuberculosis

Despite combination therapy is effective in treating tuberculosis (TB) caused by susceptible Mycobacterium tuberculosis (Mtb) strains, overcoming multidrug resistance (MDR) remains a problem. As a result, it is critical to continue developing new chemotherapeutic drugs with unique mechanisms of action. A variety of benzimidazole-linked thiazole compounds was designed and developed for the treatment of Mtb in this work using a molecular hybridization approach. The newly synthesized compounds demonstrated potent anti-TB action against drug-resistant Mtb strains. Compounds 4g and 4h are more effective against MDR clinical isolates (CDCT-16 and CDCT-27) than isoniazid, with MIC ranges ranging from 3.68 to 8.15 µM. Other derivatives demonstrated moderate to good anti-TB efficacy against MDR clinical isolates. The cytotoxicity findings recommend that this class of compounds is rated as low. Further SAR analysis reveals that electron-withdrawing groups on the thiazole ring of the compounds are essential. The findings were also connected with molecular docking studies, which provided models for the inhibitors strong interactions with the mycobacterial membrane protein large 3 (MmpL3), which is a critical member in the formation of the Mtb stiff cell wall. Compounds potential ADMET descriptors, drug score and drug-likeness properties were validated by in-silico predictions.

Design, synthesis, in vitro biological assessment and molecular modeling insights for novel 3-(naphthalen-1-yl)-4,5-dihydropyrazoles as anticancer agents with potential EGFR inhibitory activity

Currently, the humanity is in a fierce battle against various health-related challenges especially those associated with human malignancies. This created the urge to develop potent and selective inhibitors for tumor cells through targeting specific oncogenic proteins possessing crucial roles in cancer progression and survive. In this respect, new series of pyrazole-thiazol-4-one hybrids (9a–p) were synthesized as potential anticancer agents. All the synthesized molecules exhibited potent antiproliferative actions against breast cancer (BC) T-47D and MDA-MB-231 cell lines with IC50 ranges 3.14–4.92 and 0.62–58.01, respectively. Moreover, the most potent anti-proliferative counterparts 9g and 9k were assessed against EGFR. They displayed nanomolar inhibitory activity, IC50 267 ± 12 and 395 ± 17 nM, respectively. Worth noting, both compounds 9g and 9k induced apoptosis in MDA-MB-231 cells, and resulted in a cell cycle arrest at G2/M phase. Furthermore, an in silico analysis including docking and molecular dynamic simulations was performed.

Rational synthesis, anticancer activity, and molecular docking studies of novel benzofuran liked thiazole hybrids.

A novel series of benzofuran bearing thiazole hybrids were synthesized by the multistep reaction approach. All synthesized molecules were selected by the National Cancer Institute, USA for one-dose anticancer activity against 60 various human cancer cell lines indicating nine types of cancer. Among thirteen compounds, two compounds showed higher lethality, so, it was selected for five-dose anticancer screening against all cancer cell lines. Compound 8g and 8h were displayed remarkable antiproliferative activity with GI50 values ranging from 0.295 to 4.15μM and LC50 values ranging from 4.43 to > 100μM. All data are compared with standard drugs fluorouracil and doxorubicin. Compound 8g showed higher potency as a cytotoxic molecule then fluorouracil. Furthermore, all new hybrids were studied for molecular docking into the active binding sites of 1HOV protein.

Synthesis and Evaluation of Some New 4H-Pyran Derivatives as Antioxidant, Antibacterial and Anti-HCT-116 Cells of CRC, with Molecular Docking, Antiproliferative, Apoptotic and ADME Investigations.

Colorectal cancer oncogenesis is linked to dysbiosis, oxidative stress and overexpression of CDK2. The 4H-pyran scaffold is considered an antitumoral, antibacterial and antioxidant lead as well as a CDK2 inhibitor. Herein, certain 4H-pyran derivatives were evaluated as antibacterial, antioxidant and cytotoxic agents against HCT-116 cells. Derivatives 4g and 4j inhibited all the tested Gram-positive isolates, except for B. cereus (ATCC 14579), with lower IC50 values (µM) than ampicillin. In addition, 4g and 4j demonstrated the strongest DPPH scavenging and reducing potencies, with 4j being more efficient than BHT. In cell viability assays, 4d and 4k suppressed the proliferation of HCT-116 cells, with the lowest IC50 values being 75.1 and 85.88 µM, respectively. The results of molecular docking simulations of 4d and 4k, inhibitory kinase assays against CDK2, along with determination of CDK2 protein concentration and the expression level of CDK2 gene in the lysates of HCT-116 treated cells, suggested that these analogues blocked the proliferation of HCT-116 cells by inhibiting kinase activity and downregulating expression levels of CDK2 protein and gene. Moreover, 4d and 4k were found to induce apoptosis in HCT-116 cells via activation of the caspase-3 gene. Lastly, compounds 4g, 4j, 4d and 4k were predicted to comply with Lipinski’s rule of five, and they are expected to possess excellent physiochemical and pharmacokinetic properties suitable for in vivo bioavailability, as predicted by the SwissADME web tool.

Synthesis, characterization and antioxidant activities of novel N-substituted pyrazoline derivatives bearing 3-benzo[b]thiophene and 5-styryl substituents

The new series of N-substituted pyrazoline derivatives bearing benzo[b]thiophene and styryl with trifluoromethyl substitution at para- and meta- positions were synthesized. The structures of newly synthesized compounds were characterized by UV, IR, NMR, Mass and single crystal XRD (SCXRD) and had been screened for antioxidant activity. The in vitro antioxidant activities screening revealed that hydroxyl radical scavenging (HRS) activities of compounds 3c, 3f, 4a, 4e, 4f, 5c, 5d 5e and 5g are stronger than the other compounds and the compound 5g shows much better antioxidant activity.

Design and synthesis of aryl-piperidine derivatives as potent and selective PET tracers for cholesterol 24-hydroxylase (CH24H)

Cholesterol 24-hydroxylase (CH24H, CYP46A1) is a cytochrome P450 family enzyme that maintains the homeostasis of brain cholesterol. Soticlestat, a potent and selective CH24H inhibitor, is in development as a therapeutic agent for Dravet syndrome and Lennox-Gastaut syndrome. Herein, we report the discovery of aryl-piperidine derivatives as potent and selective CH24H positron emission tomography (PET) tracers which can be used for dose guidance of a clinical CH24H inhibitor and as a diagnostic tool for CH24H-related pathology. Starting from compound 1 (IC50 = 16 nM, logD = 1.7), which was reported as a CH24H inhibitor with lower lipophilicity, a18F-labeling site (3-fluoroazetidine) was incorporated by structure-based drug design (SBDD) utilizing the co-crystal structure of a compound 1 analog. Subsequent optimization to adjust key parameters for PET tracers, such as potency, lipophilicity, brain penetration, and unbound plasma protein binding, enabled compounds 3f (IC50 = 8.8 nM) and 3g (IC50 = 8.7 nM) as PET imaging candidates. Selectivity of these compounds for CH24H was validated by a brain distribution study using CH24H-WT and KO mice. In non-human primate PET imaging, [18F]3f and [18F]3g showed similar regional uptake in the brain, indicating that these tracers were specific to the CH24H-expressed regions and validated the expression of CH24H in the living brain by different tracers.

Synthesis of N-Methylene Linker Containing Phthalimide Bearing-1H-1,2,3-Triazole by Click Chemistry Approach: Anticancer Activity in Human Cells

The novel series of phthalimide-1H-1,2,3-triazole derivatives (6a–o) was created by combining various azide derivatives with an N-methylene bond using click chemistry. N-alkylation procedures using a base catalyst were used to make the initial alkyne. 1H NMR, 13C NMR, IR, mass spectrometry, and elemental analysis methods were used to comprehensively characterize all intermediates and final products. The antitumor efficacy of reported hybrids of two heterocyclic rings, phthalimide and 1,2,3-triazole in a single structure, was tested against nine basic cancer panels as well as the NCI-60 cell line. The compounds 6a, 6b, 6e, 6g, 6h, and 6j showed potent anticancer activity in vitro against Leukemia, non-small cell lung cancer, renal cancer, and melanoma cancer cell lines, with GI50 values ranging from −61.57 to 12.07 µM. The antimicrobial activity of fractions was tested. Further to gain an insight into the mechanism of action molecular docking study was performed against Epidermal Growth Factor Receptor Tyrosine Kinase which could provide valuable insights into the key thermodynamic interactions.

Access to new phosphonate- and imidazolidine-benzopyrimidinone derivatives as antityrosinase and anti-acetylcholinesterase agents: Design, synthesis and molecular docking

To discover new acetylcholinesterase and tyrosinase inhibitors, a series of dialkyl phosphonate-benzopyrimidinones 4a-b was prepared via Michaelis-Arbuzov rearrangement (Arbusov reaction) of benzopyrimidinone chloride 2 with trialkyl phosphate, as well as a series of imidazolidine-benzopyrimidinone derivatives 5a-g synthesized by Mannich reaction of 2-((arylamino)methyl) benzopyrimidin-4(3H)-one 3 with formaldehyde. The structures of the new target compounds were investigated by 1H NMR, 13C NMR and ESI-HRMS. All synthesized compounds were evaluated for their anti-acetylcholinesterase and antityrosinase activities. Compounds 5f, 3g and 4b showed the highest tyrosinase inhibition and compounds 3g, 3d and 5g were found to be the most anti-acetylcholinesterase agents. Moreover, structure activity relationship (SAR) was discussed for all synthesized compounds and the interaction modes of the most potent inhibitors were confirmed through molecular docking studies.

Synthesis, biological evaluation, and molecular docking analysis of novel 1, 3, 4-thiadiazole -based kojic acid derivatives as tyrosinase inhibitors

Kojic acid is a natural tyrosinase inhibitor that has been clinically used to cure hyperpigmentation in humans. However, kojic acid as a hydrophilic small-molecule has deficient inhibitory activity and stability. In this current work, a new series of kojic acid derivatives, 4a–h bearing 2-amino-5-mercapto-1,3,4-thiadiazole, were synthesized using TBTU as the catalyst, and their chemical structures were characterized by spectroscopic methods. The inhibitory activities of synthesized compounds against Mushroom tyrosinase were evaluated in vitro, and some derivatives showed potent anti-tyrosinase activity. In particular, compounds 4g (IC50=10.71 ± 2.47 µM) and 4h (IC50=18.62 ± 3.05 µM) were comparable with the reference compound, kojic acid (IC50=23.14 µM). The Docking study was in good agreement with experimental results and indicated that compound 4g interacted entirely with the active site of tyrosinase with proper binding energy and mode.

Design, synthesis, characterization, molecular docking studies and anticancer activity evaluation of novel hydrazinecarbothioamide, 1,2,4-triazole-3-thione, 4-thiazolidinone and 1,3,4-oxadiazole derivatives

A series of novel hydrazinecarbothioamide, 1,2,4-triazole-3-thione, 4-thiazolidinone and 1,3,4-oxadiazole derivatives were synthesized and evaluated for their cytotoxic activity against A549 lung adenocarcinoma cells and L929 normal mouse fibroblast cell line. The structural elucidation of the compounds was performed and verified by IR spectroscopy, 1H-NMR, 13C-NMR, mass and elemental analysis. Compound 3a, 3b, 3c, 3d, 3e, 3g and 3i displayed the best anticancer activity against A-549 cell line. The anticancer activities of 3a, 3c, 3d, 3e, 3g and 3i were determined as better than the positive control Cisplatin. In addition to the in vitro analysis, molecular docking studies were employed to explore the possible binding interactions of the title compounds with B-DNA (PDB ID: 1BNA) dodecamer d(CGCGAATTCGCG)2. Structure-activity relationships, as well as virtual ADME studies, were carried out and a relationship between biological, electronic, and physicochemical qualifications of the target compounds was determined. Consequently, these derivatives present a leading structure for future drug development due to their straightforward synthesis and relevant bioactivity.

Facile synthesis of 8-arylated quercetin derivatives and biological activity evaluation

The synthesis of a novel library of 8-arylated quercetin derivatives bearing phenolic hydroxyl group applying Suzuki-Miyaura cross-coupling reaction between 8-iodoquercetin methyl ether and various methoxyl and / or fluorine substituted aryl boronic acids is reported. Corresponding 8-arylated quercetin derivatives were synthesized in a five-step reaction sequence consisting of acid hydrolysis of commercially cheap rutin, followed by O-methylation of the obtained quercetin with dimethyl sulfate. After iodination of quercetin methyl ether with N-Iodosuccinimide (NIS), the resulting 8-iodoquercetin proved to be effective electrophile in reactions with various methoxyl and/or fluorine substituted aryl boronic acids. Finally, the 8-arylated permethylated quercetin ethers underwent de-methylation to provide polyphenolic derivatives. The obtained quercetin derivatives were well characterized by the 1H NMR, 13C NMR and HRMS data. Preliminary biological evaluations showed that some of the synthesized 8-arylated quercetin derivatives possessed very high anti-cancer cell proliferation activity in MGC-803 and OVCAR-3 cancer cell lines (IC50< 5.0 µmol/L) as well as high activity in HCC827 cancer cell line (IC50<10 µmol/L) in vitro. Among these compounds, compound 5h with para-fluorine and ortho-methoxyl substitution exhibited best activity against MGC-803 and HCC827 (IC50 = 2.91 µmol/L, 9.42 µmol/L), respectively. while compound 6g with meta-fluorine and para-hydroxyl substitution showed best activity aganist OVCAR-3 cells (IC50 = 3.88 µmol/L). Furthermore, the 1,1-diphenyl-2-methylbenzohydrazine (DPPH) scavenging experiment showed all compounds exhibited better antioxidant activity than quercetin, in particular quercetin derivative 6f containing para-hydroxyl and meta-hydroxyl substitution. The disclosed structure-activity relationship also offers new examples for application of fluorine modifications as versatile tools in drug discovery.