Synthesis Inhibitory Activity Research Articles

Synthesis and Acetylcholinesterase Inhibitory Activity of Novel Trilaciclib Analogs.

Trilaciclib is a CDK4/6 inhibitor, used to treat the bone marrow damage in chemotherapy patients. A series of thirteen novel structural trilaciclib analogs was obtained to evaluate their activity against acetylcholinesterase. An effective method for the synthesis of 4,7-substituted 8,9-dihydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidine derivatives from a new methyl 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate was developed. Most of the synthesized pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidine derivatives inhibited acetylcholinesterase in the micromolar range. The obtained data can be used for designing more potent acetylcholinesterase inhibitors with the pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidine scaffold.

Design, Synthesis, and Hypoxia-Inducible Factor-1α Inhibitory Activity Evaluation of Panaxadiol Derivatives Containing a Thiazole Moiety.

The hypoxia-inducible factor-1α (HIF-1α) pathway has been implicated in tumor angiogenesis, growth, and metastasis. Therefore, the inhibition of this pathway is an important therapeutic target for cancer. Thiazole derivatives have been reported to have diverse biological activities, especially in terms of anti-tumor. Consequently, we hypothesized that the introduction of a thiazole functional group in PD was likely to improve the biological potency. Here, three series of PD derivatives containing a thiazole moiety were synthesized, including (a) sulfonyl-containing thiazole derivatives (5 a-l), (b) urea-containing thiazole derivatives (7 a-i), and (c) thiourea-containing thiazole derivatives (9 a-i), and evaluated for HIF-1α inhibitory activity using a Hep3B cell-based luciferase reporter assay. The results showed that about 1/3 of the target compounds showed moderate or strong HIF-1α inhibitory activity, among which compounds 5 d and 7 b showed the strongest inhibitory activity with IC50 values of 17.37 and 6.42 μM, respectively, and did not show any significant cytotoxicity. Western blot assay results indicated that these two compounds exhibited more potent inhibition, compared with panaxadiol, of the expression of HIF-1α protein in Hep3B cells at a concentration of 50 μM. Molecular docking experiments were also performed to investigate the structure-activity relationship. Compounds 5 d and 7 b can be used as leads for further study and development of novel antitumor drugs.

Synthesis, α-Glucosidase, α-Amylase, and Aldol Reductase Inhibitory Activity with Molecular Docking Study of Novel Imidazo[1,2-a]pyridine Derivatives.

Inhibition ofaldose reductase (AR), α-glycosidase (α-GLY), and α-amylase (α-AMY) are some of the essential targets in diabetes mellitus (DM). Here, a series of imidazo[1,2-a]pyridine-based 1,3,4-thiadiazole derivatives (8a-k) were successfully synthesized and characterized using 1H NMR, 13C NMR, and HRMS spectroscopic techniques. The inhibition effects of the synthesized derivatives against AR, α-GLY, and α-AMY were evaluated using both in vitro and in silico methods. In vitro studies revealed that the derivatives (8a-k) showed significant inhibition activity. The results showed that the novel derivatives (8a-k) demonstrated potential inhibitory activity, with K I values covering the following ranges: 23.47 ± 2.40 to 139.60 ± 13.33 nM for AR and 6.09 ± 0.37 to 119.80 ± 12.31 μM for α-GLY, with IC50 values 81.14 to 153.51 μM for α-AMY. Furthermore, many of these compounds exhibited high inhibition activity, while some of them showed higher potency than the reference compounds. Molecular docking of the target compounds was carried out in the active sites of AR (PDB ID: 4JIR) and α-GLY (PDB ID: 5NN8).

Synthesis, characterization and α-amylase inhibition activity of new family of tetrapodal ligands with pyrazole-tetrazole subunits

New family of tetrapodal compounds entitled 3-(bis((5-methyl-1-((2-isopentyl-2H-tetrazol-5-yl)methyl)-1H-pyrazol-3 yl)methyl)amino)propan-1-ol.(T1),2-(4-(bis((5-methyl-1-((2-propyl-2H-tetrazol-5-yl)methyl)-1H-pyrazol-3-yl)methyl)amino)phenyl)ethan-1-ol.(T2),N,N-bis((1-((2-isopentyl-2H-tetrazol-5-yl)methyl)-5-methyl-1H-pyrazol-3-yl)methyl)propan-1-amine.(T3).and.N,N-bis((1-((2-isopentyl-2H-tetrazol-5-yl)methyl)-5-methyl-1H-pyrazol-3-yl)methyl)propan-2 amine (T4) were synthesised as drug candidates to treat Type 2 diabetes. Their structures as the intermediates compounds were ensured by NMR and FTIR analysis as well as the spectrometric methods including high-resolution mass spectrometry and elemental analysis. The tetrapodal molecules were obtained in moderate yields in the range of 37–45 %. Their anti-diabetic activity was evaluated based on their α-amylase inhibition potency by determining their IC50 values. The obtained results showed that the tetrapodal compounds possess potent α−amylase inhibition activity 3 to 236 times higher than that of the acarbose, used as positive control. These findings were also supported by docking calculations.

Design, Synthesis and Cholinesterase Inhibitory Activity of Novel 1,3,4-Thiadiazole Derivatives

Inhibition of the cholinesterases (AChE and BChE) plays a pivotal role in the symptomatic treatment of Alzheimer’s disease. The present study reports the synthesis and anticholinesterase activity of five novel thiadiazole analogs in search of anti-Alzheimer agents. The structures of the newly synthesized compounds were characterized using 1H NMR, 13C NMR and HRMS. Tested compounds inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes with IC50 values in the range of 8.250-20.382 μM and 14.143-0.986 μM, respectively. N-(4-Chlorophenyl)-2-[(5-(allylamino)-1,3,4-thiadiazol-2-yl)thio]-N-(3-nitrobenzyl)acetamide (6e) was determined as the most potent inhibitor against both tested enzymes when compared with standard drug tacrine. Molecular docking study was carried out to reveal the binding interactions between compound 6e and the active site of AChE

Design, Synthesis, Anticholinesterase and Antidiabetic Inhibitory Activities, and Molecular Docking of Novel Fluorinated Sulfonyl Hydrazones.

In this study, it was aimed to synthesize (E)-N'-(2-hydroxybenzylidene)-substituted benzenesulfonohydrazide (1-7) from the 2-hydroxybenzaldehyde reaction of different substituted fluorinated sulfonyl hydrazides. The structures of the synthesized molecules were characterized by elemental analysis, FTIR, 1H NMR, 13C NMR, 19F NMR, and 2D NMR (HMBC, correlation spectroscopy, and HQSC). The anticholinesterase (AChE and BChE) and antidiabetic (α-glucosidase, α-amylase) inhibition activities of the synthesized compounds were evaluated. According to biological activity test results, (E)-N'-(2-hydroxybenzylidene)-4-(trifluoromethoxy)benzenesulfonohydrazide (compound 7 among hydrazone derivatives 1-7) demonstrated better BChE inhibitor activity than galantamine in anticholinesterase inhibition; and in the α-glucosidase and α-amylase assay, it exhibited more antidiabetic inhibition activity than the reference standard.

Design, Synthesis, and Xanthine Oxidase Inhibitory Activity of 4-(5-Aminosubstituted-4-cyanooxazol-2-yl)benzoic Acids.

Xanthine oxidase is a known therapeutic target for the treatment of hyperuricemia and related diseases. Despite the availability of current drugs such as allopurinol and febuxostat, the search for new compounds to effectively inhibit this enzyme remains relevant. In our study, 75 virtual structures of 4-(5-aminosubstituted-4-cyanooxazol-2-yl)benzoic acids with structural similarity to febuxostat were designed for evaluation of their potency against xanthine oxidase. After molecular docking simulations, eight compounds were selected for synthesis and in vitro testing. The synthesized compounds were found to exhibit in vitro xanthine oxidase inhibitory activity in the nanomolar concentration range. The most effective inhibitors with 4-benzylpiperidin-1-yl or 1,2,3,4-tetrahydroisoquinolin-2-yl substituents at position 5 of the oxazole ring had IC50 values close to that of febuxostat. The kinetic data suggest a mixed-type inhibition when the inhibitor binds preferentially to the free enzyme rather than to the enzyme-substrate complex. Molecular docking and molecular dynamic simulations were carried out to get insight into the key interactions of the inhibitors bound to the xanthine oxidase active site.

Investigations on 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,2-a]pyridazin-1-amines and related compounds: synthesis, chemical behaviour, structure elucidation and iNOS inhibitory activity.

The present work reports on the preparation of the hitherto unknown title compounds 5, with various synthetic routes described. The initially pursued concept of S-N exchange with varioius 1-substituted 3-methylsulfanyl-5,6,7,8-tetrahydro-1 H -[1,2,4]triazolo[1,2- a ]pyridazines 4 by using nitrogen nucleophiles was only marginally successful. The reactions proceeded slowly and the yields were low, mainly because of the pronounced formation of 5,6,7,8-tetrahydro-[1,2,4]triazolo[1,2- a ]pyridazin-1-imines 7 by oxidation of the heterocyclic amines 5 initially formed. The integration of the synthesis of 3-acylsulfanyl analogues with the more reactive leaving groups also failed. On the other hand, the cyclization of the hydrohalides of hexahydropyridazine-1-carboximidamide with aromatic aldehydes and some low molecular weight ketones gives significantly better results in the synthesis of the title compounds 5. The use of the hydrochloride 6b proved to be advantageous in comparison to the hydroiodide 6a because the yields were significantly better and the imines 7 formed at the same time only to a small extent. In addition, the starting compound 6b can be prepared in a single-step synthesis in very good yield from hexahydropyridazine hydrochloride 1 and cyanamide. The cyclization of N' -phenylhexahydropyridazine-1-carboximidamide hydrochloride 6c with substituted benzaldehydes gives the 3-aryl-substituted 2-phenyl-2,3,5,6,7,8-hexahydro -1H -[1,2,4]triazolo[1,2- a ] pyridazin-1-imines 8. In the context with the study of the reaction of hexahydropyridazine-1-carboximidamide hydroiodide 6a with cyclohexanone, the hexahydropyridazine-1-carboxamide 9 was specifically synthesized. This can be reacted with aromatic aldehydes to give the 5,6,7,8-tetrahydro-1 H -[1,2,4]triazolo[1,2- a ]pyridazin-1-ones 10 in very good yields. The results of the biological testing of representatives of the synthesized 5,6,7,8-tetrahydro-[1,2,4] triazolo[1,2-a]pyridazine-1-amines 5 show, in comparison to the already examined thions 3 and 3-methylsulfanyl derivatives 4, significantly less inducible nitric oxide synthase (iNOS) inhibitory activity.

Synthesis and pancreatic lipase inhibition activity evaluation ofaurone derivatives with substituents on benzylidene ring

Pancreatic lipase is an essential enzyme for the digestion and absorption of dietary fat. Inhibiting this enzyme is one of the strategies in tackling obesity. To date, orlistat is the only Food and Drug Administration (FDA)-approved drug for obesity treatment via this mechanism. Therefore, there has been a growing interest in exploring novel compounds with natural structural frameworks that can give similar activity with fewer side effects. In this study, we describe the synthesis and pancreatic lipase inhibitory activity evaluation of 10 aurone derivatives with different substituents on the benzylidene ring. Aurone derivatives were synthesised through aldol condensation of benzofuranone and corresponding benzaldehyde derivatives with medium to good yields (45-73%). Pancreatic lipase inhibitory activities of synthesized compounds were determined by UV-Vis spectroscopy with quercetin and orlistat as references. Three aurones were found to have higher I% than quercetin at the same concentration (50 μg/ml). Compound 5c (2-(5’bromo-2’-hydroxybenzylidene)benzofuran-3(2H)-one) exhibited the greatest activity (I%=60.95%), better than quercetin (I%=27.20%) at the concentration of 50 μg/ml

Synthesis, molecular modelling and choline esterase enzyme inhibitory activity of novel enaminone derivatives of sulfonamides

Synthesis, molecular modelling and choline esterase enzyme inhibitory activity of novel enaminone derivatives of sulfonamides

Synthesis and histone deacetylases inhibitory activity of pyrimidine‐based 1,3,4‐oxadiazoles

AbstractThe histone deacetylases (HDACs) are being explored as a promising therapeutic target for the treatment of various diseases. Here, the synthesis of a series of pyrimidine‐based 1,3,4‐oxadiazoles, in which the oxadiazole scaffold is attached to the pyrimidine ring via a methyleneoxy spacer, is described and their HDAC inhibitory activity studied. The target compounds were synthesized by sequence of reactions involving O‐alkylation of 2‐(methylthio)pyrimidin‐4(3H)‐ones with ethyl 2‐bromoethanoate followed by oxidation of the 2‐methylthio group, displacement of the obtained 2‐methylsulfonyl group with amines, hydrazinolysis of the obtained ethyl (2‐amino‐substituted pyrimidin‐4‐yloxy)acetates to give the corresponding hydrazides and their cyclization under the treatment with ethyl O‐ethyl xanthate or carbonyldiimidazole to 1,3,4‐oxadiazole‐2(3H)‐thiones and 1,3,4‐oxadiazol‐2(3H)‐one, correspondingly. In addition, two 1,3,4‐oxadiazole‐2(3H)‐thiones were converted into (N3)‐morpholinomethyl derivatives by the Mannich reaction with formaldehyde and morpholine. The yields of intermediates and target compounds ranged from moderate to excellent. The synthesized compounds were characterized by 1H and 13C NMR spectra and HRMS data, their purity was controlled by TLC. The synthesized pyrimidine‐based 1,3,4‐oxadiazoles (18 compounds) were tested as inhibitors of the HDAC4 and HDAC8 isoforms and their inhibitory activity was compared with that of Vorinostat. Most of the oxadiazolethiones containing methyl group at the position 6 of the pyrimidine moiety were found to be more selective towards HDAC8, while oxadiazolethiones with propyl group in the pyrimidine ring were active against HDAC4. Among the tested compounds, 5‐((2‐(dibutylamino)‐6‐propylpyrimidin‐4‐yloxy)methyl)‐1,3,4‐oxadiazole‐2(3H)‐thione (48) was found to have the strongest inhibitory activity for HDAC4 isoform (IC50 = 4.2 μM vs. IC50 = 59 μM for Vorinostat) while 5‐((2‐(cyclopentylamino)‐6‐propylpyrimidin‐4‐yloxy)methyl)‐1,3,4‐oxadiazole‐2(3H)‐thione (50) was the most potent HDAC8 inhibitor (IC50 = 6.8 μM).

Novel antipyrine substituted 4-thiazolidinones: Synthesis, DNA binding and topoisomerase inhibition activities, and in-silico studies

In this study, we report the synthesis and characterization of novel 4-thiazolidinones containing antipyrine (3a-e) derived from the starting compounds of Schiff bases (2a-e). The Schiff bases were synthesized using aldehydes of natural origin, such as citronellal, cuminaldehyde, 2-thiazolecarboxaldehyde, 5-methylfurfural, and syringaldehyde. Their FTIR spectra revealed the enol- tautomeric solid-state structures of compounds 3b and 3d. The pUC18 plasmid DNA binding specificity and capacity of the compounds to catalytically generate topoisomerase I activity were also examined using agarose gel electrophoresis. The compounds induced changes in DNA mobility and showed a topoisomerase I inhibitory effect at all doses. 4-Thiazolidinones had a higher affinity in DNA and topoisomerase I than the Schiff bases. DNA binding and topoisomerase I activities were most effective at low concentration (6 μM) for the compounds of Schiff bases 2a, d, and 4-thiazolidinones 3a, d. Furthermore, this study presents computational methods for addressing the molecules’ drug-like properties. 2a, d, and 3a, d Compounds were used as representative of the most bioactive among the newly synthesized molecules in in-silico studies. The web tools of ADMETlab, SwissADME, OSIRIS, and the BOILED-Egg method were used to conduct in-silico biological studies involving ADME prediction, BBB penetration, gastrointestinal absorption, and toxicity studies. The ADME profile of the query compounds gets within the range of applicability and is at an appropriate level. In-silico studies revealed that compounds 2a, d, and 3a, d are neither hERG blockers nor AMES toxic. However, compounds 2a and 3a have hepatotoxicity.

Synthesis, characterization, and MAO inhibitory activities of three new drug-like N-acylhydrazone derivatives

In this study, three new N-acylhydrazone derivatives with the structural motif of N'-(substitutedbenzylidene)-3-(5-methyl-2-benzoxazolinon-3-yl)propanehydrazide (5a-c) are prepared and evaluated for their MAO inhibitory activities. The structures of the synthesized compounds are elucidated through spectral methods (IR, 1H-NMR, 13C-NMR), elemental analysis and single crystal X-ray crystallography. Detailed structural and Hirshfeld surface analyses of compounds (5a-c) have provided further insights into their molecular and crystal structures and also their intermolecular interactions. Complementing the spectral and structural analyses confirmed the E-configurations of the compounds in the solid state. The Hirshfeld surface analyses of the crystal structures have indicated that the most important contributions for the crystal packings are from H ... H, H … C/C … H and H … O/O … H (for 5a-c) and H … F/F … H (for 5b and c). In vitro tests are revealed their MAO inhibitory activities, surpassing reference compounds moclobemide and selegiline. Notably, synthesized N-acylhydrazone derivatives (5a-c) are exhibited superior MAO inhibitory activities, with a higher selectivity for MAOB over MAOA (SI >10). Molecular docking studies are provided insights into the binding modes of the compounds in the active site of the target enzyme. Theoretical ADME (Absorption, Distribution, Metabolism and Excretion), gastrointestinal absorption and blood-brain barrier permeation studies revealed that the compounds possess pharmacological attributes resembling those of typical drugs. This properties and MAO inhibitory activities of N-acyl hydrazone derivatives emphasize their potentials as promising candidates in the field of medicinal chemistry.

Synthesis, Characterization and Glyoxalase Inhibitory Activity of 4,6-Diheteroarylpyrimidine-2-amine Derivatives: In Vitro and In Silico Studies

Synthesis, Characterization and Glyoxalase Inhibitory Activity of 4,6-Diheteroarylpyrimidine-2-amine Derivatives: In Vitro and In Silico Studies

In Vitro Biological Activities and Relative Chemicals in Different Extracts of Licorice and Fermenting Licorice

Purpose: This paper aims to qualitatively and quantitatively analyze the differences between the main chemicals in different licorice and fermented licorice (FL) extracts and their <i>in vitro</i> skin care activities and active ingredients. To evaluate the effect of fermentation on the efficacy of licorice.Methods: The DPPH free radical scavenging activity, mushroom tyrosinase activity, tyrosinase activity of B16F10 cells, and melanin synthesis inhibition activity of different extracts treated by fermentation and different extracts without fermentation treatment were evaluated. The effects of ethyl acetate components (EaF) including glycyrrhizin, isoglycyrrhizin, liquiritoside, isoliquiritigenin and glycyrrhizin ketone A on melanin synthesis were tested in vitro. Further assessment of FL at stromal metalloproteinase-1 (MMP-1) levels in human dermal fibroblasts (HDF).Results: Glycyrrhizin, isoglycyrrhizin, liquiritoside, isoliquiritigenin were improved in FL, and the antioxidant and MMP-1 inhibitory activities of FL controls were significantly increased.Conclusion: After fermentation, the anti-aging effect of licorice was greatly improved, indicating that the fermentation process had a good effect on improving the efficacy of licorice.

Impact of Lubumbashi's solar irradiation and ambient air on the quality and pharmacological value of root barks from four of the most used medicinal plants

BackgroundThe quality of medicinal plant products is highly dependent on drying conditions, which can lead to contaminated drugs, and/or with considerable phytochemical and pharmacological variations. In Lubumbashi (a very sunny city with polluted air), the used medicinal plants are exposed to the sun and ambient air for drying or on the sales premises, but the real impact of solar energy and ambient air on the quality and pharmacological value of exposed medicinal plant samples has never been studied. ObjectiveThis study seeks to determine the impact of solar irradiation and ambient air in Lubumbashi on the quality, and biological activities of samples from the most used medicinal plants in Lubumbashi/DR Congo. MethodsThe root barks of single-plant samples from Terminalia mollis M.A.Lawson, Securidaca longepedunculata Fresen, Oldfieldia dactylophylla (Welw. ex Oliv.) J.Léonard. and Phyllanthus muellerianus (Kuntze) Exell. were dried in the sun, oven, and shade respectively. Mineral and microbial contamination were assessed. In addition, phytochemical and pharmacological analyses were also done. ResultsSamples exposure to ambient air led to mineral contamination, with the appearance of highly toxic elements such as As, and a significant increase in others such as Al, Co, Cr, Cu, Ni, and Pb. Microbial contamination exceeded admissible limits in some samples and varied according to drying conditions and species, of which S. longepedunculata was the most contaminated. The levels of total phenols, flavonoids, and terpenoids varied significantly according to drying conditions and species. For example, in T. mollis, total phenols increased from 457.6 ± 2.33 to 536.4 ± 1.56 mg GAEq/g in fresh samples exposed to the sun for 10 days, total flavonoids increased from 455.2 ± 16.49 to 617.1 ± 14.29 mg QEq/g when dry samples were exposed to the sun for 10 days; total terpenoids decreased significantly compared to the shade-dried sample. Biological activity also varied according to species and experimental conditions. For example, an increase in activity against S. aureus (from 11.00 ± 1.00 to 17.33 ± 0.58 mm) was observed in the fresh sample of P. muellerianus exposed to sunlight for 10 days, while increases in hemozoin synthesis inhibitory (from 44.6 ± 3.9 to 52.7 ± 2.4 %) and antiradical activity (from 23.7 ± 0.7 to 29.5 ± 0.1 %) were observed in the fresh S. longepedunculata sample exposed to the sun for 5 days. ConclusionExposure of the studied medicinal plant samples to ambient air in the environmental conditions of Lubumbashi would result in worrying mineral contamination and drying of these samples in the sun in the above-mentioned region, in the oven, or the shade would result in variations, some of which are negative, in certain secondary metabolites and biological activities.

Synthesis and Urease Inhibition Activities of Some New Schiff Bases Benzimidazoles Containing Thiophene Ring

Synthesis and Urease Inhibition Activities of Some New Schiff Bases Benzimidazoles Containing Thiophene Ring

Synthesis, Characterization, Antibacterial Evaluation, and Enzyme Inhibition Activity of a Novel Nitrogen-containing Heterocyclic Sulfonamide

Synthesis, Characterization, Antibacterial Evaluation, and Enzyme Inhibition Activity of a Novel Nitrogen-containing Heterocyclic Sulfonamide

Synthesis and Monoamine Oxidase Inhibitory Activity of Halogenated Flavones.

Small molecule neurotransmitters containing amines are metabolized by monoamine oxidase (MAO) in the nervous system. Monoamine oxidase inhibitors are a valuable class of drugs prescribed for the management of neurological disorders, including depression. A series of halogenated flavonoids similar to the dietary flavonoid acacetin were designed as selective MAO-B inhibitors. MAO-A and -B inhibition of 36 halogenated flavones were tested. The halogens (fluorine and chlorine) were placed at positions 5 and 7 on ring A of the flavone scaffold. All compounds were selective MAO-B inhibitors with micro- and nanomolar IC50 values. Compounds 9f, 10a-c, 11a-c, 11g,h, and 11l displayed inhibitory activity toward MAO-B with IC50 values between 16 to 74 nM. We conclude that halogenated flavonoids are promising molecules in pursuit of developing new agents for neurological disorders.

Synthesis and Tyrosinase Inhibitory Activity of Novel Benzimidazole/Thiazolidin-4-one Hybrid Derivatives.

In this study, novel 3-(phenylamino)thiazolidin-4-one 2 a-d and 3-(phenyl)thiazolidin-4-one 3 a-g derivatives which are having benzimidazole moiety were synthesized and their tyrosinase inhibitory activity were investigated. The structures of the target compounds were elucidated using 1 H/13 C-NMR, IR and MS. The structure of 2 b was also characterized using HSQC NMR technique. Among the target compounds, 3 b-g demonstrated stronger tyrosinase inhibitory activity (IC50 values for 3 b-g ranged from 80.93 to 119.20 μM), compared to the positive control kojic acid (IC50 : 125.08 μM). With IC50 value of 80.93 μM, 5-(2-(4-(1H-benzimidazol-1-yl)phenyl)-4-oxothiazolidin-3-yl)-2-methylbenzenesulfonamide 3 g was found to be the most active derivative of the series. Molecular docking studies were conducted to elucidate the binding interactions between compounds and tyrosinase. The MTT assay studies used to determine the cytotoxicity of 3 b-g showed that 3 c, 3 d, 3 f and 3 g were not cytotoxic in the range of 0-200 μM. Considering its tyrosinase inhibitory activity and cytotoxic effect, 3 g exhibits promising potential for further research and development as a novel tyrosinase inhibitor.