New Benzimidazole-Triazole Derivatives as Topoisomerase I Inhibitors: Design, Synthesis, Anticancer Screening, and Molecular Modeling Studies.

In this study, we designed, synthesized, and evaluated a series of 1,2,4-triazole benzimidazoles for their cytotoxic effects against the A549, C6, and NIH3T3 cell lines. Additionally, these compounds were assessed for their inhibitory activity against DNA topoisomerase I, aiming to develop novel anticancer agents. The synthesized final compounds 4a-h were characterized using 1H NMR, 13C NMR, and HRMS. Among them, compounds 4b and 4h emerged as the most potent agents against the A549 cell line, exhibiting an IC50 value of 7.34 ± 0.21 µM and 4.56 ± 0.18 µM, respectively. These results were compared to standard drugs, doxorubicin (IC50 = 12.420 ± 0.5 µM) and Hoechst 33342 (IC50 = 0.422 ± 0.02 µM). Notably, all tested compounds displayed higher cytotoxicity toward A549 cells than C6 cells. Compounds 4b and 4h demonstrated significant inhibitory activity against topoisomerase I, highlighting their potential as lead compounds in anticancer therapy. Subsequent in silico molecular docking studies were conducted to elucidate the potential binding interactions of compounds 4b and 4h with the target enzyme topoisomerase I. Molecular dynamics studies also assessed and validated the binding affinity and stability. These studies confirmed the promising binding affinity of these compounds, reinforcing their status as lead candidates. According to DFT, compound 4b having the lower energy gap value (ΔE = 3.598 eV) is more chemically reactive than the others, which is consistent with significant inhibitory activity against topoisomerase I. Furthermore, in silico ADME profiles for compounds 4b and 4h were evaluated using SwissADME, providing insights into their pharmacokinetic properties.

Design, synthesis, and biological activity studies of carbonic anhydrase inhibitors.

Carbonic anhydrase (CA) enzymes are a common catalytic enzyme in many organisms. Vertebrates and invertebrates have different CA isoforms. Sixteen different isozymes of the α-CA isoform found in vertebrates have been identified so far. The main task of this enzyme is to catalyze the reversible conversion of carbon dioxide into bicarbonate and hydrogen ions in the body. It is widely distributed in many organs and tissues. They are involved in important physiological processes such as pH and CO2 homeostasis, biosynthetic reactions such as gluconeogenesis, lipogenesis, ureagenesis, bone resorption, calcification, tumorigenicity, and electrolyte secretion. As a result of the literature research, it has been determined that the most effective inhibitor of the carbonic anhydrase enzyme is sulfonamides. The R group in the general molecular structure of R-SO2-NH2 generally consists of aromatic or heteroaromatic ring systems. The sulfonamides interact strongly with the Zn2+ ions in the active site of the enzyme. In this study, 10 sulfonamide derivatives were synthesized. Analyses of the obtained compounds are evaluated by using 1H NMR, 13C NMR and HRMS spectroscopic methods. The inhibition effect of the obtained compounds on the carbonic anhydrase enzyme was investigated by means of in vitro kit method. For the selected compounds, docking studies were performed and the enzyme active sites and binding points were determined. It was revealed that the strongest interaction with CA enzymes (CA-I, CA-II, CA-IX, CA-XII) active sites was observed with the compound 2e.

Design, synthesis, biological activities, and evaluation of molecular docking-dynamics studies of new thiosemicarbazones that may be effective against Alzheimer's disease.

Donepezil is one of the most used drugs in the treatment of Alzheimer's disease. Its activity as an AChE inhibitor makes new studies with these enzyme inhibitors attractive. For this purpose, in this study, 12 compounds including thiosemicarbazone pharmacophore, have been synthesized for the treatment of the Alzheimer's disease. 3,4-Dimethoxybenzene or 1,3-benzodioxolone rings were used for the PAS region. The substituted piperazine benzene structure is preferred for the CAS region. At the same time, the thiosemicarbazone pharmacophore structure with known ChE enzyme inhibition potential was used as a bridge connecting the CAS and PAS regions. Structure determination of compounds 3a-3l were revealed using 13 C-NMR, 1 H-NMR, and HRMS spectroscopic methods. The inhibition profile of obtained compounds (3a-3l) against ChE was evaluated using in vitro modified Ellman method. Compounds 3a, 3b, 3f, 3g and 3i exhibited inhibitory activity against the AChE enzyme. Compound 3a showed the highest inhibitory potential with an IC50 = 0.030 ± 0.001 µM. As a result of molecular docking studies, compound 3a displayed important interactions compared to other active derivatives. Molecular dynamics studies are important to see the stability of the complex formed by ligand and protein. RMSD, RMSF ang Rg parameters were calculated via dynamic studies. In conclusion, compound 3a may be a potential AChE enzyme inhibitor with its strong inhibitory potential and behavior in silico.

Synthesis and Anticancer Activities of Pyrazole-Thiadiazole-Based EGFR Inhibitors.

Lung cancer is one of the most common cancer types of cancer with the highest mortality rates. However, while epidermal growth factor receptor (EGFR) is an important parameter for lung cancer, EGFR inhibitors also show great promise in the treatment of the disease. Therefore, a series of new EGFR inhibitor candidates containing thiadiazole and pyrazole rings have been developed. The activities of the synthesized compounds were elucidated by in vitro MTT, (which is chemically 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), cytotoxicity assay, analysis of mitochondrial membrane potential (MMP) by flow cytometry, and EGFR inhibition experiments. Molecular docking and molecular dynamics simulations were performed as in silico studies. Compounds 6d, 6g, and 6j showed inhibitor activity against the A549 cell line with IC50 = 5.176 ± 0.164; 1.537 ± 0.097; and 8.493 ± 0.667 µM values, respectively. As a result of MMP by flow cytometry, compound 6g showed 80.93% mitochondrial membrane potential. According to the results of the obtained EGFR inhibitory assay, compound 6g shows inhibitory activity on the EGFR enzyme with a value of IC50 = 0.024 ± 0.002 µM.

Synthesis, Antifungal Activities, Molecular Docking and Molecular Dynamic Studies of Novel Quinoxaline-Triazole Compounds.

Uncontrolled use of antifungal drugs affects the development of resistance to existing drugs. Azole antifungals constitute a large part of antifungal therapy. Therefore, there is a need for new azole antifungals. Within the scope of this study, 17 new triazole derivative compounds were synthesized. Structure determinations were clarified by spectroscopic analysis methods (1H-NMR, 13C-NMR, HRMS). In addition, structure matching was completed using two-dimensional NMR techniques, HSQC, HMBC and NOESY. The antifungal effects of the compounds were evaluated on Candida strains by means of in vitro method. Compound 5d showed activity against Candida glabrata with a MIC90 = 2 µg/mL. Compound 5d showed activity against Candida krusei with a MIC90 = 2 µg/mL. This activity value, which is higher than fluconazole, is promising. In addition, the biofilm inhibition percentages of the compounds were calculated. Molecular docking and molecular dynamics simulations performed with compound 5d are in harmony with activity studies.

Synthesis of Imidazole-2,3-dihydrothiazole Compounds as VEGFR-2 Inhibitors and Their Support with in Silico Studies.

In this study, 12 novel 2-((1-(4-(1H-imidazol-1-yl)phenyl)ethylidene)hydrazineylidene)-3-ethyl-4-(substitutephenyl)-2,3-dihydrothiazole derivatives were obtained. Among these compounds, 2-((1-(4-(1H-imidazol-1-yl)phenyl)ethylidene)hydrazineylidene)-4-([1,1'-biphenyl]-4-yl)-3-ethyl-2,3-dihydrothiazole (4h) was chosen as the most active derivative in the series. According to the MTT results, compounds 4h and 4k showed activity with IC50 =4.566±0.246 µM and IC50 =4.537±0.463 µM, respectively. Unlike other derivatives, compound 4h carries a phenyl ring in the 4th position of the phenyl ring. This bulky group allowed the compound to settle in the enzyme active site. Dynamic studies show that the stability of the compound does not change over 40 ns. RMSD, RMSF and Rg parameters all remained within acceptable limits. The uninterrupted aromatic hydrogen bonding of the enzyme active site with the important amino acids Cys919, Glu885 and Asp1046 proves the inhibitory potential of compound 4h on the VEGFR-2 enzyme. It is thought that more active compounds will be reached with the derivatives to be synthesized starting from compound 4h.

Design, synthesis, evaluation of biological activities and molecular docking and dynamic studies of novel acetazolamide analog compounds.

Modification of drugs used in the clinic is a frequently used method with regards to medicinal chemistry in the development of new drugs. Acetazolamide is a drug in clinical use as a CA inhibitor. Within the scope of this study, the 'N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl) acetamide' structure, which is acetazolamide residue, was kept constant; various mercaptan substitutions were made from methylene adjacent to the carbonyl group in the structure. Compounds 4c, 4d, 4e, 4 g, 4h, 4i, and 4j exhibited inhibitor activity against CA enzyme with IC50=0.238 ± 0.010, 0.161 ± 0.007, 0.067 ± 0.002, 0.084 ± 0.003, 0.033 ± 0.001, 0.049 ± 0.002 and 0.187 ± 0.008 µM, respectively. The intermolecular interactions of the promising compounds with aromatase enzyme were investigated through the SP docking approach, which revealed significant binding interaction energies associated with these compounds. To measure the stability of the compounds in the enzyme active site, dynamic studies were performed at 100 ns. In addition to the RMSD, RMSF parameters, the interaction ratios of compound 4h with amino acids in the enzyme active site and the interaction histograms were also investigated. The results obtained are quite promising. Continuous interactions were exhibited with Thr199, Glu106, His96, His94 and His119, which are important for the CA enzyme.Communicated by Ramaswamy H. Sarma.

Synthesis of new compounds bearing methyl sulfonyl pharmacophore as selective COX-2 inhibitor.

Cyclooxygenase, also known as prostaglandin H2 synthase (PGH2), is one of the most important enzymes in pharmacology because inhibition of COX is the mechanism of action of most nonsteroidal anti-inflammatory drugs. In this study, ten thiazole derivative compounds had synthesized. The analysis of the obtained compounds was performed by 1 H NMR and 13 C NMR methods. By this method, the obtained compounds could be elucidated. The inhibitory effect of the obtained compounds on cyclooxygenase (COX) enzymes was investigated. The encoded compounds 5a, 5b, and 5c were found to be the most potent compared to the reference compounds ibuprofen (IC50 = 5.589 ± 0.278 µM), celecoxib (IC50 = 0.132 ± 0.004 µM), and nimesulide (IC50 = 1.692 ± 0.077 µM)against COX-2 isoenzyme. The inhibitory activity of 5a, 5b, and 5c is approximate, but the 5a derivative proved to be the most active in the series with an IC50 value of 0.180 ± 0.002 µM. The most potent COXs inhibitor was 5a, which was further investigated for its potential binding mode by a molecular docking study. Compound 5a was found to be localized at the active site of the enzyme, like celecoxib, which has a remarkable effect on COXs enzymes.

Design, synthesis, and molecular docking studies of novel quinoxaline derivatives as anticancer agents.

As lung cancer was placed foremost part among other types of cancer in terms of mortality. Recent researches are widely focused on developing multi-targeted and site-specific targeted drug designs. In the present study, we designed and developed a series of quinoxaline pharmacophore derivatives as active EGFR inhibitors for the treatment of non-small cell lung cancer. The compounds were synthesized through a condensation reaction between hexane-3,4-dione and methyl 3,4-diaminobenzoate as a first step. Their structures were confirmed by 1 H-NMR, 13 C-NMR, and HRMS spectroscopic methods. Cytotoxicity (MTT) were applied to determine anticancer activity of the compounds against breast (MCF7), fibroblast (NIH3 T3), and lung (A549) cell lines as EGFR inhibitors. Doxorubicin was used as a reference agent, compound 4i exhibited a significant effect among other derivatives with IC50 = 3.902 ± 0.098 µM value against A549 cell line. The docking study showed that the best position on EGFR receptor could be observed with 4i. From the obtained evaluations of the designed series, compound 4i was a promising agent as EGFR inhibitor for further investigation and evaluation studies in the future.

Design, Synthesis, and Biological Evaluation Studies of Novel Naphthalene-Chalcone Hybrids As Antimicrobial, Anticandidal, Anticancer, and VEGFR-2 Inhibitors.

Cancer is a progressive disease that is frequently encountered worldwide. The incidence of cancer is increasing with the changing living conditions around the world. The side-effect profile of existing drugs and the resistance developing in long-term use increase the need for novel drugs. In addition, cancer patients are not resistant to bacterial and fungal infections due to the suppression of the immune system during the treatment. Rather than adding a new antibacterial or antifungal drug to the current treatment plan, the fact that the drug with anticancer activity has these effects (antibacterial and antifungal) will increase the patient's quality of life. For this purpose, in this study, a series of 10 new naphthalene-chalcone derivatives were synthesized and their anticancer-antibacterial-antifungal properties were investigated. Among the compounds, compound 2j showed activity against the A549 cell line with an IC50 = 7.835 ± 0.598 µM. This compound also has antibacterial and antifungal activity. The apoptotic potential of the compound was measured by flow cytometry and showed apoptotic activity of 14.230%. The compound also showed 58.870% mitochondrial membrane potential. Compound 2j inhibited VEGFR-2 enzyme with IC50 = 0.098 ± 0.005 µM. Molecular docking studies of the compounds were carried out by in silico methods against VEGFR-2 and caspase-3 enzymes.

Design, synthesis and molecular docking and ADME studies of novel hydrazone derivatives for AChE inhibitory, BBB permeability and antioxidant effects.

Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease that is characterized by memory and cognitive impairments that predominantly affects the elderly and is the most common cause of dementia. As is known, the AChE enzyme consists of two parts. In this work, 10 new hydrazones (3a-3j) were designed and synthesized. Naphthalene, indole, benzofuran and benzothiophene rings were used to interact with the PAS region. 4-fluorophenyl and 4-fluorobenzyl structures were preferred for interaction with the CAS region. In biological activity studies, the AChE and BChE inhibitory potentials of all compounds were evaluated using the in vitro Ellman method. The biological evaluation showed that compounds 3i and 3j displayed significant activity against AChE. The compounds 3i and 3j displayed IC50 values of 0.034 and 0.027 µM against AChE, respectively. The reference drug donepezil (IC50 = 0.021 µM) also displayed a significant inhibition against AChE. In addition, the antioxidant activities of the compounds were also evaluated. Derivatives 3i and 3j, which emerged active from both in vitro activity studies, were subjected to in vitro PAMPA tests to determine BBB permeability. Further docking simulation also revealed that these compounds (3i, 3j and donepezil) interacted with the enzyme active site in a similar manner to donepezil. A few parameters derived from MD simulation trajectories were computed and validated for the protein-ligand complex's stability under the dynamic conditions.Communicated by Ramaswamy H. Sarma.

Design, Synthesis, and In Vitro and In Silico Approaches of Novel Indanone Derivatives as Multifunctional Anti-Alzheimer Agents.

Alzheimer's disease (AD) is a neurological, progressive illness that typically affects the elderly and is clinically distinguished by memory and cognitive decline. Due to a number of factors, including the absence of a radical treatment, an increase in the patient population over time, the high cost of care and treatment, and a significant decline in patients' quality of life, the importance of this disease has increased. These factors have all prompted increased interest among researchers in this field. The chemical structure of the donepezil molecule, the most popular and effective treatment response for AD, served as the basis for the design and synthesis of 42 novel indan-1-one derivatives in this study. Using IR, 1H, and 13C NMR as well as mass spectroscopic techniques, the compounds' structures were identified. Research on the compounds' antioxidant activities, cholinesterase (ChE) enzyme inhibition, monoamine oxidase (MAO) A and B inhibitory activities, ß-amyloid plaque inhibition, and cytotoxicity impact was carried out. Inhibition of ß-amyloid plaque aggregation; effective inhibition of AChE, BChE, and MAO-B enzymes; and significant antioxidant activity were all demonstrated by compounds D28-D30 and D37-D39. Because of their various actions, it was hypothesized that the related compounds may be useful in treating AD symptoms as well as providing palliative care.

Synthesis of novel thiosemicarbazone derivatives and investigation of their dual AChE and MAO-B inhibitor effects.

In this study, 15 thiosemicarbazone derivatives were synthesized. Analysis of the obtained compounds was performed by means of 1 H-NMR, 13 C-NMR and high resolution mass spectroscopy (HRMS) spectroscopic methods. The inhibition effect of the obtained compounds on cholinesterase and monoaminoxidase (MAO) enzymes were investigated with in vitro methods. None of the compounds showed significant activity on the butyrylcholinesterase enzyme. On the other hand, compounds 3b, 3c, 3e, 3k, 3l, 3m, 3n and 3o displayed significant activity on acetylcholinesterase (AChE) while compounds 3f, 3i, 3k, 3l, 3m, 3n, 3o also showed remarkable effects on monoamine oxidase-B (MAO-B) enzymes. For the selected compounds, docking studies were performed and the enzyme active site and binding modes were determined. It was revealed that the strongest interaction with AChE and MAO-B enzyme active sites was observed with the compound 3k. Another important factor in the treatment of diseases affecting the central nervous system such as Alzheimer's is the ability of the compounds to cross the blood-brain barrier (BBB). Additionally, the agents planned for the treatment of these diseases must also pass the blood-brain barrier. Therefore, in silico BBB penetration properties of active compounds were investigated.

Synthesis of novel benzothiazole derivatives and investigation of their enzyme inhibitory effects against Alzheimer's disease.

The use of dual acetylcholinesterase (AChE)-monoamine oxidase B (MAO-B) inhibitors is a new approach in the treatment of Alzheimer disease (AD). In this work, 14 new benzothiazoles (4a-4n) were designed and synthesized. In biological activity studies, the AChE, butyrylcholinesterase (BChE), MAO-A and MAO-B inhibitory potentials of all compounds were evaluated using the in vitro fluorometric method. Additionally, amyloid beta (Aß)-aggregation inhibitory effects of active compounds were evaluated by means of an in vitro kit-based method. The biological evaluation showed that compounds 4a, 4d, 4f, 4h, 4k and 4m displayed significant activity against AChE and MAO-B enzymes. Compound 4f displayed inhibitory activity against AChE and MAO-B enzyme with IC50 values of 23.4 ± 1.1 nM and 40.3 ± 1.7 nM, respectively. It has been revealed that compound 4f may have the potential to inhibit AChE and MAO-B enzymes, as well as the ability to prevent the formation of beta amyloid plaques accumulated in the brains of patients suffering from AD. In silico studies also support the obtained biological activity findings. Compound 4f provided strong interactions with the active site of both enzymes. In particular, the interaction of compound 4f with flavin adenine dinucleotide (FAD) in the MAO-B enzyme active site is a promising and exciting finding.

Synthesis of new derivatives containing pyridine, investigation of MAO inhibitory activities and molecular docking studies.

In this study, novel pyridine-containing thiazolyl hydrazone derivatives were synthesized. Structure determinations of the compounds were performed using 1H NMR, 13C NMR and HRMS techniques. The biological activities of the compounds were evaluated against MAO enzymes by in vitro fluorometric method. As a result of activity studies, compound 3a showed selective inhibitory activity against MAO-B enzyme with IC50 = 0.088 + 0.003 µM. The selectivity index of this compound is greater than 1136. Molecular docking studies were carried out using 2V5Z crystal. It has been observed that docking studies and activity studies are in harmony.

Synthesis of New Pyrimidine-Triazole Derivatives and Investigation of Their Anticancer Activities.

Aromatase inhibitors are the most used anticancer drug group in breast cancer cases. The development of resistance in cancer patients over time and the side effects of existing drugs make the need for new and effective agents permanent. In this study, 10 novel pyrimidine-triazole derivatives were synthesized and their anticancer activities were investigated. Compounds 5c and 5g showed inhibitor activity against MCF-7 cell line with IC50 =1.573±0.020; 3.698±0.056 µM value, respectively. As a result of in vitro aromatase enzyme inhibition test, compounds 5c and 5g were exhibited significant activity with IC50 =0.082±0.007 µM and IC50 =0.198±0.015 µM, respectively. Estimated physicochemical parameters were calculated using the online SwissADME program for all compounds. Interaction modes of the compounds 5c and 5g were investigated against aromatase enzyme by means of docking studies. As a result of the studies, the importance of the triazole ring for aromatase inhibition has been understood.

Design, synthesis, and biological activity of novel dithiocarbamate-methylsulfonyl hybrids as carbonic anhydrase inhibitors.

Carbonic anhydrase (CA) enzymes are involved in many physiological events. These enzymes, which contain Zn2+ in their structure, can be easily inhibited by dithiocarbamate compounds. In addition, CA enzyme inhibitory activities are known in groups such as sulfonamide and methylsulfonyl. For this purpose, in this study, a series of 23 new dithiocarbamate-methylsulfonyl derivatives were synthesized and their CA enzyme inhibitory activities were investigated. The inhibition potentials of the obtained compounds against the human CA I and CA II enzymes were investigated by the in vitro enzyme isolation method. It is seen that the compounds show activity at the nanomolar level. Molecular docking studies of the compounds were carried out by in silico methods. The poses of compounds 2a, 2e, 2o, and 2t are presented.

Design, Synthesis, and Evaluation of Novel 2H-Benzo[b][1,4]thiazin-3(4H)-one Derivatives as New Acetylcholinesterase Inhibitors.

Alzheimer's disease (AD) is a slowly progressive neurodegenerative disease that causes dementia in people aged 65 and over. In the present study, a series of thiadiazole hybrid compounds with benzothiazine derivatives as acetylcholinesterase inhibitors were developed and evaluated for their biological activity. The AChE and BChE inhibition potentials of all compounds were evaluated by using the in vitro Ellman method. The biological evaluation showed that compounds 3i and 3j displayed significant inhibitory activity against AChE. Compounds 3i and 3j showed IC50 values of 0.027 µM and 0.025 µM against AChE, respectively. The reference drug donepezil (IC50 = 0.021 µM) also showed significant inhibition against AChE. Further docking simulation also revealed that these compounds (3i and 3j) interacted with the active site of the enzyme similarly to donepezil. The antioxidant study revealed that compounds 3i and 3j exhibited greater antioxidant effects. An in vitro blood-brain barrier permeability study showed that compounds 3i and 3j are promising compounds against AD. The cytotoxicity study of compounds 3i and 3j showed non-cytotoxic with an IC50 value of 98.29 ± 3.98 µM and 159.68 ± 5.53 µM against NIH/3T3 cells, respectively.

Design, synthesis, molecular docking and molecular dynamics studies of novel triazolothiadiazine derivatives containing furan or thiophene rings as anticancer agents.

Breast cancer is the most common cancer type amoung post-menopausal women. Aromatase inhibitors were used in the treatment of patients. However, drug resistance may develop in long-term drug use, especially in 3rd and 4th stage (advanced) cancer cases. Therefore, there is a constant need for new agents. In this study, new triazolothiadiazine derivatives were synthesized and their anticancer activities were investigated. Compounds 2k, 2s, and 2w showed inhibitor activity against MCF-7 cell line with IC50 = 4.63 ± 0.10; 2.23 ± 0.16; 3.13 ± 0.08 µM value, respectively. As a result of in vitro aromatase enzyme inhibition test, compound 2s was the most active derivative with IC50 = 0.058 ± 0.023 µM. In addition, DNA synthesis inhibition percentages of the compounds were measured by the BrdU method. The intermolecular interactions of the promising compounds with aromatase enzyme were investigated through the SP docking approach, which revealed significant binding interaction energies associated with these compounds. Following that, the interaction's stability was assessed using a typical atomistic 100 ns dynamic simulation study. A number of parameters derived from MD simulation trajectories were computed and validated for the protein-ligand complex's stability under the dynamic conditions.

Design, synthesis, biological activity, molecular docking, and molecular dynamics of novel benzimidazole derivatives as potential AChE/MAO-B dual inhibitors.

To develop new acetylcholinesterase (AChE)-monoamine oxidase-B (MAO-B) dual inhibitors against Alzheimer's disease, the benzimidazole ring, which has a propargyl side chain with previously proven selective MAO-B inhibitory activity, was used as the main structure. Moreover, like donepezil, it was thought that the enzyme AChE would provide π-π interactions with the peripheral anionic side in this structure. Piperazine derivatives were chosen for the cationic active site. The synthesis of the compounds was carried out in five steps. The structures of the compounds were determined using 1 H-NMR (nuclear magnetic resonance), 13 C-NMR, and high-resolution mass spectrometry spectroscopic methods. First, the in vitro AChE, butyrylcholinesterase (BChE), MAO-A, and MAO-B inhibitory potentials of the obtained compounds were investigated. As a result of activity tests, compounds 5b, 5e, 5g, and 5h showed inhibitory activity against AChE; compounds 5e and 5g showed inhibitory activity against MAO-B. None of the compounds showed inhibitory activity against BChE or MAO-A. Compounds 5e and 5g showed dual inhibition. Among these compounds, compound 5g had inhibition potential similar to that of donepezil and selegiline. For compound 5g, further kinetic studies and Aß-plaque inhibitory potentials were investigated using in vitro methods. Molecular docking studies were performed using both AChE and hMAO-B crystals to elucidate the compound's interactions with the enzyme active site. The binding modes of the compound on AChE were fully elucidated by molecular dynamics studies.