Synthesis and Biological Evaluation of a Series of 2‐((1‐substituted‐1H‐1,2,3‐triazol‐4‐yl)methylthio)‐6‐(naphthalen‐1‐ylmethyl)pyrimidin‐4(3H)‐one As Potential HIV‐1 Inhibitors

A series of novel S‐DABO derivatives with the substituted 1,2,3‐triazole moiety on the C‐2 side chain were synthesized using the simple and efficient CuAAC reaction, and biologically evaluated as inhibitors of HIV‐1. Among them, the most active HIV‐1 inhibitor was compound 4‐((4‐((4‐(2,6‐dichlorobenzyl)‐5‐methyl‐6‐oxo‐1,6‐dihydropyrimidin‐2‐ylthio)methyl)‐1H‐1,2,3‐triazol‐1‐yl)methyl)benzenesulfonamide ( B5b7) , which exhibited similar HIV‐1 inhibitory potency (EC₅₀ = 3.22 μm ) compared with 3TC (EC₅₀ = 2.24 μm ). None of these compounds demonstrated inhibition against HIV‐2 replication. The preliminary structure–activity relationship (SAR) of these new derivatives was discussed briefly.     

Click chemistry based regioselective one‐pot synthesis of coumarin‐3‐yl‐methyl‐1,2,3‐triazolyl‐1,2,4‐triazol‐3(4H)‐ones as newer potent antitubercular agents

Coumarin‐3‐yl‐methyl‐1,2,3‐triazolyl‐1,2,4‐triazol‐3(4H)‐ones ( 8k‐z ) were synthesized via copper(I)‐catalyzed azide‐alkyne cycloaddition click chemistry. The synthesized hybrid molecules were characterized by spectral studies. Compounds 8k‐z were screened for their in vitro anti‐TB activity by using the Microplate Alamar Blue assay and for cytotoxicity using the MTT assay. Some of the compounds were found to be most potent against the tested Mycobacterium tuberculosis H37Rv strain with a MIC of 1.60 µg/ml. Further, docking the compounds into the InhA binding pocket showed strong binding interactions and effective overall docking scores were recorded. The drug‐likeness and toxicity studies were computed using Molinspiration and Protox, respectively.     

Amino Acid Derivatives,Part 4: Synthesis and Anti‐HIV Activity of New Naphthalene Derivatives

A new series of 2‐(naphthalen‐2‐yloxy)‐N‐[(aryl‐5‐thioxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐3‐yl)methyl] acetamides 5a–f was synthesized from naphthalene‐derived glycine derivative 2 via the hydrazinoacetamide analogs 4a–f . Alternatively, treatment of 4a with H₂SO₄ afforded 2‐(naphthalen‐2‐yloxy)‐N‐((5‐(phenylamino)‐1,3,4‐thiadiazol‐2‐yl)methyl) acetamide 6a . Alkylation or sulphonylation of 5a afforded the S‐alkylated derivatives 7 and 8 , respectively. Interestingly, treatment of 3 with methoxide ion gave the triazine derivative 9 . The synthesized compounds have been screened for their inhibitory activity against HIV‐1 and HIV‐2 in MT‐4 cells. However, 7 was found to be the potent inhibitor in vitro for the replication of HIV‐1 (EC₅₀ = 0.20 μg/mL), suggesting a new lead in the development of an antiviral agent.     

Synthesis and in‐vitro Cytotoxicity of Poly‐functionalized 4‐(2‐Arylthiazol‐4‐yl)‐4H‐chromenes

A new series of 4‐aryl‐4H‐chromenes bearing a 2‐arylthiazol‐4‐yl moiety at the 4‐position were prepared as potential cytotoxic agents. The in‐vitro cytotoxic activity of the synthesized 4‐aryl‐4H‐chromenes was investigated in comparison with etoposide, a well‐known anticancer drug, using MTT colorimetric assay. Among them, the 2‐(2‐chlorophenyl)thiazol‐4‐yl analog 4b showed the most potent activity against nasopharyngeal epidermoid carcinoma KB, medulloblastoma DAOY, and astrocytoma 1321N1, and compound 4d bearing a 2‐(4‐chlorophenyl)thiazol‐4‐yl moiety at the 4‐position of the chromene ring exhibited the best inhibitory activity against breast cancer cells MCF‐7, lung cancer cells A549, and colon adenocarcinoma cells SW480 with IC₅₀ values less than 5 μM. The ability of compound 4b to induce apoptosis was confirmed in a nuclear morphological assay by DAPI staining in the KB and MCF‐7 cells.     

Discovery of Novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole Derivatives as Potential Anti‐Inflammatory Agents

A novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole derivative 5 with good anti‐inflammatory activity was identified from our in‐house library. Based on hit compound 5 , two series of 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole derivative 6a – g and 7a – h were designed and synthesized as novel anti‐inflammatory agents. Most of synthesized compounds exhibited good inhibitory activity on NO and TNF‐α production in LPS‐stimulated RAW 264.7 macrophages, in which the compound 6e showed most potent inhibitory activity on NO (IC₅₀ = 0.86 μm ) and TNF‐α (IC₅₀ = 1.87 μm ) production. Further evaluation revealed that compound 6e displayed more potent in vivo anti‐inflammatory activity than ibuprofen did on xylene‐induced ear oedema in mice. Additionally, Western blot analysis revealed that compound 6e could restore phosphorylation level of IκBα and protein expression of p65 NF‐κB in LPS‐stimulated RAW 264.7 macrophages.     

Synthesis and Biological Evaluation of Kojic Acid Derivatives Containing 1,2,4‐triazole as Potent Tyrosinase Inhibitors

A series of 5‐substituted‐3‐[5‐hydroxy‐4‐pyrone‐2‐yl‐methymercapto]‐4‐amino‐1,2,4‐triazole derivatives were synthesized by nucleophilic substitution reaction of 5‐hydroxy‐2‐chloromethyl ‐4H‐pyran‐4‐one with 5‐substituted‐3‐mercapto‐4‐amino‐1,2,4‐triazole, and their inhibitory effects on mushroom tyrosinase were evaluated. The results indicated that most of the synthesized compounds exhibited significant inhibitory activity. Specifically, 5‐(4‐chlorophenyl)‐3‐[5‐hydroxy‐4‐pyrone‐2‐yl‐methymercapto]‐4‐amino‐1,2,4‐triazole ( 6j ) exhibited the most potent tyrosinase inhibitory activity with IC₅₀ value of 4.50 ± 0.34 μm . The kinetic studies of the compound ( 6j ) demonstrated that the inhibitory effects of the compound on the tyrosinase were belonging to competitive inhibitors. Meanwhile, the structure–activity relationship was also discussed.     

Synthesis and Biological Evaluation of [1,2,4]Triazolo[3,4‐a]phthalazine and Tetrazolo[5,1‐a]phthalazine Derivatives Bearing Substituted Benzylpiperazine Moieties as Positive Inotropic Agents

Two series of [1,2,4]triazolo[3,4‐a]phthalazine and tetrazolo[5,1‐a]phthalazine derivatives bearing substituted benzylpiperazine moieties have been synthesized and evaluated for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. The majority of the derivatives exhibited better in vitro activity than the existing drug, milrinone, and 6‐((4‐(4‐methoxyphenyl)piperazin‐1‐yl)methyl)tetrazolo[5,1‐a]phthalazine. 8 m in particular was identified as the most potent with an increased stroke volume of 12.02 ± 0.20% (milrinone: 2.46 ± 0.07%) at a concentration of 3 × 10^–5 m . The chronotropic effects of the compounds that exhibited good potency were also evaluated.     

Design,synthesis, and biological evaluation of 5‐(4‐(pyridin‐4‐yl)‐1H‐1,2,3‐triazol‐1‐yl)benzonitrile derivatives as xanthine oxidase inhibitors

A series of 5‐(4‐(pyridin‐4‐yl)‐1H‐1,2,3‐triazol‐1‐yl)benzonitrile derivatives ( 1a–p ) was designed, synthesized, and identified as xanthine oxidase inhibitors with micromolar level potencies. Among them, the most promising compounds 1j and 1k were obtained with IC₅₀ values of 8.1 and 6.7 μm , respectively. The Lineweaver–Burk plot revealed that compound 1k acted as a mixed‐type xanthine oxidase inhibitor. SAR analysis revealed that a carbon atom occupying the X³ position is not as effective as a nitrogen atom, and an iso‐pentyloxy or a cyclopentyloxy at the 2‐position of benzonitrile moiety will benefit the inhibitory potency. The basis of xanthine oxidase inhibition by 1k was rationalized by molecular modeling studies.     

Synthesis and Positive Inotropic Evaluation of 2‐(4‐(4‐Substituted benzyloxy)‐3‐methoxybenzyl)‐1,4‐diazepan‐1‐yl)‐N‐(4,5‐dihydro‐1‐methyl[1,2,4]triazolo[4,3‐a]quinolin‐7‐yl)‐acetamides

In an attempt to search for more potent positive inotropic agents, a series of 2‐(4‐(4‐substituted benzyloxy)‐3‐methoxybenzyl)‐1,4‐diazepan‐1‐yl)‐N‐(4,5‐dihydro‐1‐methyl[1,2,4]triazolo[4,3‐a]quinolin‐7‐yl)acetamides was synthesized and their positive inotropic activities were evaluated by measuring left atrium stroke volume on isolated rabbit‐heart preparations. Several compounds showed favorable activity compared with the standard drug Milrinone among which 2‐(4‐(4‐(2‐chlorobenzyloxy)‐3‐methoxybenzyl)‐1,4‐diazepan‐1‐yl)‐N‐(4,5‐dihydro‐1‐methyl‐[1,2,4]triazolo[4,3‐a]quinolin‐7‐yl)acetamide 6e was found to have the most desirable potency with the 6.79 ± 0.18% increased stroke volume (Milrinone: 1.67 ± 0.64%) at a concentration of 1×10^–5 M in our in‐vitro study. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.     

The synthesis of three isotopomers of 2‐methyl‐2‐(4‐[3‐[1‐(4‐methylbenzyl)‐5‐oxo‐4,5‐dihydro‐1H‐[1,2,4]triazol‐3‐yl]propyl]phenoxy)propionic acid,a potent and selective peroxisome proliferator‐activated receptor alpha agonist

Although fenofibrate ( 1a ) is commercially available and clinically effective in lowering serum triglycerides, its activity and sub‐type selectivity at the PPARα receptors are only moderate; therefore, there exists a need for more potent and sub‐type selective PPARα agonists. To that end, discovery efforts have identified 2‐methyl‐2‐(4‐[3‐[1‐(4‐methylbenzyl)‐5‐oxo‐4,5‐dihydro‐1H‐[1,2,4]triazol‐3‐yl]propyl]phenoxy)propionic acid ( 2 ), a potent and selective human PPARα receptor agonist. In support of pre‐clinical ADME studies and bioanalysis, three isotopomers of 2 have been synthesized. The results of these efforts are described below. Copyright © 2007 John Wiley & Sons, Ltd.     

Synthesis and kinetics studies of N′‐(2‐(3,5‐disubstituted‐4H‐1,2,4‐triazol‐4‐yl)acetyl)‐6/7/8‐substituted‐2‐oxo‐2H‐chromen‐3‐carbohydrazide derivatives as potent antidiabetic agents

A novel series of N′‐(2‐(3,5‐disubstituted‐4H‐1,2,4‐triazol‐4‐yl)acetyl)‐6/7/8‐substituted‐2‐oxo‐2H‐chromen‐3‐carbohydrazides were synthesized and studied for their α‐glucosidase inhibition activity. Most of the synthesized compounds exhibited potential α‐glucosidase inhibition activity with IC₅₀ values ranging from 0.96 ± 0.02 to 32.86 ± 0.73 µg/ml. Among them, compounds 3e and 4e , having a methoxy group on the coumarin ring, proved to be the most potent ones, showing an enzyme inhibition activity with IC₅₀ = 0.96 ± 0.02 and 1.44 ± 0.06 µg/ml, respectively. The kinetic study through Lineweaver–Burk plots revealed that the inhibition mechanism of the most active compounds 3d, 3e, 4d , and 4e , on the α‐glucosidase activity, was found to be in the competitive mode.     

Synthesis and Anti‐neuroinflammatory Activity of Lactone Benzoyl Hydrazine and 2‐nitro‐1‐phenyl‐1H‐Indole Derivatives as p38α MAPK Inhibitors

Inhibition of p38 mitogen‐activated protein kinases (MAPKs) would allow significant modulation of the neuroinflammation condition associated with Alzheimer's disease (AD). Inspired from the pharmacophore of natural NF‐κB and p38α MAPK inhibitor 5,6‐dehydrokawain and p38α MAPK inhibitors 1a, 1‐pyrazolyl‐3‐(4‐((2‐anilinopyrimidin‐4‐yl)oxy)napththalen‐1‐yl)ureas, and 1b , a class of indole–pyrimidinyl compounds which were patented respectively, we designed, de novo synthesized, and evaluated two kinds of novel series of lactone benzoyl hydrazine derivatives and 2‐nitro‐1‐phenyl‐1H‐indole derivatives in an effort to develop pharmacologically tractable agents to alleviate the progression of AD. Fourteen of the seventeen synthesized compounds exhibit significant inhibitory effect on the nitric oxide (NO) production induced by lipopolysaccharide (LPS)‐induced microglia activation with IC₅₀ less than the control 5,6‐dehydrokawain. Notably, compound 27 , 6‐methoxy‐2‐nitro‐1‐(1H‐1, 2, 3‐triazol‐1‐yl)‐1H‐indole, with IC₅₀ values of 1.6  μ m can markedly inhibit p38 α MAPK and NO release in BV‐2 microglial cells. The molecular dynamic (MD) simulations demonstrate that compound 27 inhibits p38 α MAPK through binding to the Glu71 and Asp168 residues. Moreover, in vitro study shows that all compounds can easily cross the blood–brain barrier (BBB) and did not exhibit any acute cellular toxicity checked by MTT assay. These investigations provide promising chemical lead candidate as anti‐neuroinflammatory agents for AD.     

2‐Aryl‐3‐(1H‐Azol‐1‐yl)‐1H‐Indole Derivatives: A New Class of Antimycobacterial Compounds – Conventional Heating in Comparison with MW‐Assisted Synthesis

2‐Aryl‐3‐(1H‐imidazol‐1‐yl and 1H‐1,2,4‐triazol‐1‐yl)‐1H‐indole derivatives were synthesized and tested for their in‐vitro antifungal and antimycobacterial activities. These indole derivatives were devoid of antifungal activity against the tested strains of Candida spp. Yet, they exhibited an interesting antitubercular activity against Mycobacterium tuberculosis reference strain H₃₇Rv.     

Synthesis,In Vitro Protoporphyrinogen Oxidase Inhibition,and Herbicidal Activity of N‐(Benzothiazol‐5‐yl)hexahydro‐1H‐isoindole‐1,3‐diones and N‐(Benzothiazol‐5‐yl)hexahydro‐1H‐isoindol‐1‐ones

Protoporphyrinogen oxidase ( EC 1.3.3.4 ) is one of the most significant targets for a large family of herbicides. As part of our continuous efforts to search for novel protoporphyrinogen oxidase‐inhibiting herbicides, N‐(benzothiazol‐5‐yl)tetrahydroisoindole‐1,3‐dione was selected as a lead compound for structural optimization, leading to the syntheses of a series of novel N‐(benzothiazol‐5‐yl)hexahydro‐1H‐isoindole‐1,3‐diones ( 1a – o ) and N‐(benzothiazol‐5‐yl)hexahydro‐1H‐isoindol‐1‐ones ( 2a – i ). These newly prepared compounds were characterized by elemental analyses, ¹H NMR, and ESI‐MS, and the structures of 1h and 2h were further confirmed by X‐ray diffraction analyses. The bioassays indicated that some compounds displayed comparable or higher protoporphyrinogen oxidase inhibition activities in comparison with the commercial control. Very promising, compound 2a , ethyl 2‐((6‐fluoro‐5‐(4,5,6,7‐tetrahydro‐1‐oxo‐1H‐isoindol‐2(3H)‐yl)benzo[d]thiazol‐2‐yl)‐sulfanyl)acetate, was recognized as the most potent candidate with K_i value of 0.0091 μm . Further greenhouse screening results demonstrated that some compounds exhibited good herbicidal activity against Chenopodium album at the dosage of 150 g/ha.     

Design,Synthesis, and Antitumor Activity of (E,Z)‐1‐(dihydrobenzofuran‐5‐yl)‐3‐phenyl‐2‐(1,2,4‐triazol‐1‐yl)‐2‐propen‐1‐ones

A series of (E,Z)‐1‐(dihydrobenzofuran‐5‐yl)‐3‐phenyl‐2‐(1,2,4‐triazol‐1‐yl)‐2‐propen‐1‐ones ( C1 – C35 ) were designed and synthesized, and the structures of compounds (Z)‐ C27 and (Z)‐ C29 were confirmed by single‐crystal X‐ray diffraction. The antitumor activities of these novel compounds against cervical cancer (HeLa), lung cancer (A549), and breast cancer (MCF‐7) cell lines were evaluated in vitro. Majority of the title compounds exhibited strong antitumor activities and were much more promising than the positive control Taxol, which were also accompanied by lower cytotoxicity to normal cells. In particular, compounds (E,Z)‐ C24 exhibited the most consistent potent activities against three neoplastic cells with IC₅₀ values ranging from 3.2 to 7.1 μm . Further researches demonstrated that compounds (E,Z)‐ C24 could induce cell apoptosis and arrest cell cycle at the G2/M and S phases. Meanwhile, the structure–activity relationship between the configurations and cytotoxicity of the compounds was also investigated.     

Design and synthesis of 4′‐((5‐benzylidene‐2,4‐dioxothiazolidin‐3‐yl)methyl)biphenyl‐2‐carbonitrile analogs as bacterial peptide deformylase inhibitors

Herein, we report the synthesis and screening of 4′‐((5‐benzylidene‐2,4‐dioxothiazolidin‐3‐yl)methyl)biphenyl‐2‐carbonitrile analogs 11(a–j) as bacterial peptide deformylase (PDF) enzyme inhibitors. The compounds 11b (IC₅₀ value = 139.28 μm ), 11g (IC₅₀ value = 136.18 μm ), and 11h (IC₅₀ value = 131.65 μm ) had shown good PDF inhibition activity. The compounds 11b (MIC range = 103.36–167.26 μg/mL), 11g (MIC range = 93.75–145.67 μg/mL), and 11h (MIC range = 63.61–126.63 μg/mL) had also shown potent antibacterial activity when compared with standard ampicillin (MIC range = 100.00–250.00 μg/mL). Thus, the active derivatives were not only PDF inhibitors but also efficient antibacterial agents. To gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 11(a–j) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. The results suggest that this class of compounds has potential for development and use in future as antibacterial drugs.     

Design and synthesis of 9H‐fluorenone based 1,2,3‐triazole analogues as Mycobacterium tuberculosis InhA inhibitors

We prepared fifty various 9H‐fluorenone based 1,2,3‐triazole analogues varied with NH, –S–, and –SO₂– groups using click chemistry. The target compounds were characterized by routine analytical techniques, ¹H, ¹³CNMR, mass, elemental, single‐crystal XRD ( 8a ) and screened for in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H37Rv strain and two “wild” strains Spec. 210 and Spec. 192 and MIC₅₀ was determined. Further, the compounds were evaluated for MTB InhA inhibition study as well. The final analogues exhibited minimum inhibitory concentration (MIC) ranging from 52.35 to >295 μm . Among the –NH– analogues, one compound 5p (MIC 58.34 μm ), among –S– containing analogues four compounds 8e (MIC 66.94 μm ), 8f (MIC 74.20 μm ), 8g (MIC 57.55 μm ), and 8q (MIC 56.11 μm ), among –SO₂– containing compounds one compound 10p (MIC 52.35 μm ) showed less than MTB MIC 74.20 μm : Compound 4‐(((9H‐fluoren‐9‐yl)sulfonyl)methyl)‐1‐(3,4,5‐trimethoxyphenyl)‐1H‐1,2,3‐triazole ( 10p ) was found to be the most active compound with 73% InhA inhibition at 50 μm ; it inhibited MTB with MIC 52.35 μm . Further, 10f and 10p were docked to crystal structure of InhA to know binding interaction pattern. Most active compounds were found to be non‐cytotoxic against HEK 293 cell lines at 50 μm .     

Synthesis and Anticonvulsant Properties of New Mannich Bases Derived from 3‐Aryl‐pyrrolidine‐2,5‐diones. Part 1

A series of new Mannich bases of N‐[(4‐arylpiperazin‐1‐yl)‐methyl]‐3‐(chlorophenyl)‐pyrrolidine‐2,5‐diones 10–23 have been synthesized and evaluated for their anticonvulsant activity in maximum electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure threshold tests. Their neurotoxicity was determined using a rotorod screen. Several molecules showed a promising anticonvulsant profile especially in the MES‐test. In this model of seizures, the most active were N‐[{4‐(4‐chlorophenyl)‐piperazin‐1‐yl}‐methyl]‐3‐(3‐chlorophenyl)‐pyrrolidine‐2,5‐dione 16 and N‐[{4‐(3‐trifluoromethylphenyl)‐piperazin‐1‐yl}‐methyl]‐3‐(3‐chlorophenyl)‐pyrrolidine‐2,5‐dione 17 with ED₅₀ values of 21.4 mg/kg and 28.83 mg/kg, respectively. Selected derivatives 10 , 14 , and 16 were tested in the psychomotor seizure 6‐Hz test from which N‐[{4‐(2‐chlorophenyl)‐piperazin‐1‐yl}‐methyl]‐3‐(2‐chlorophenyl)‐pyrrolidine‐2,5‐dione 10 revealed the highest protection with an ED₅₀ of 78 mg/kg. Compounds 10 , 12 , and 17 were also tested in the pilocarpine‐induced status PIPS test. Furthermore, 17 was examined in the hippocampal kindling screen after i. p. administration to rats.     

Synthesis and Positive Inotropic Evaluation of (E)‐2‐(4‐Cinnamylpiperazin‐1‐yl)‐N‐(1‐substituted‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinolin‐7‐yl)acetamides

A series of (E)‐2‐(4‐cinnamylpiperazin‐1‐yl)‐N‐(1‐substituted‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinolin‐7‐yl)acetamides were synthesized and evaluated for their positive inotropic activity by measuring the left atrium stroke volume on isolated rabbit heart preparations. This class of compounds presented favorable in vitro activity compared with the standard drug, milrinone, among which N‐(1‐(3‐chlorophenyl)‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinolin‐7‐yl)‐2‐(4‐cinnamylpiperazin‐1‐yl)acetamide 5e was found to be the most potent with 16.58 ± 0.11% increased stroke volume (milrinone: 2.46 ± 0.07%) at a concentration of 3 × 10^?5 M. The chronotropic effects of the compounds having inotropic effects were also evaluated.     

Novel 1,3‐oxazine‐tetrazole hybrids as mushroom tyrosinase inhibitors and free radical scavengers: Synthesis,kinetic mechanism,and molecular docking studies

A variety of 5‐(2H‐tetrazol‐5‐yl)‐4‐thioxo‐2‐(substituted phenyl)‐4,5‐dihydro‐1,3‐oxazin‐6‐ones ( 3a–k ) have been synthesized from 1,3‐oxazine‐5‐carbonitriles ( 2a–k ). The protocol represents an efficient, facile, and novel route from easily available precursors to unprecedented structures that share 1,3‐oxazine and tetrazole motifs of utmost value. All the synthesized compounds ( 3a–k ) were evaluated for their inhibitory potential against mushroom tyrosinase. Results revealed that all examined 1,3‐oxazine‐tetrazole hybrids exhibited significant tyrosinase inhibitory activity while compound 3d having 2‐bromophenyl moiety was the most potent among the series with IC₅₀ value 0.0371 ± 0.0018 μM as compared to the reference kojic acid (IC₅₀ = 16.832 ± 0.73 μM). Inhibitory kinetics showed that compound 3d behaves as a competitive inhibitor. The molecular docking analysis was performed against target protein to investigate the binding mode. Moreover, compounds 3j and 3k displayed superior DPPH radical scavenging activity than other analogues.