The rich redox activities of phthalocyanines pave the way for the use of these structures as functional materials, particularly in applications requiring electron transfer. Therefore, improving the redox properties of these structures through the metal centers and substituents present in the structure is of great importance. For this purpose, in this study, we synthesized peripheral manganese (III) (OX-MnIIIClPc), cobalt (II) (OX-CoIIPc), and copper (II) (OX-CuIIPc) phthalocyanine compounds containing 1,3,4-oxadiazole and characterized with the FT-IR, MALDI-TOF, and UV-Vis spectroscopy to determine their structures. Then the electrochemical characterizations of MPc compounds (OX-MnIIICl/CoII/CuIIPcs) were carried out in solution using various voltammetric and spectroelectrochemical techniques. These characterization results supported preparations of the complexes successfully with the proposed structures. The cyclic voltammetry (CV), square wave voltammetry (SWV), and controlled potential coulometry (CPC) measurements indicated the common predicted reduction and oxidation reactions of the Pc ring and metal centers, which also supported the proposed structures. Voltammetric responses showed enhancements of the redox richness of the Pc ring with the extra redox reactions of Co2+ and Mn3+ cations of the OX-CoIIPc and OX-MnIIIClPc compounds. For the OX-CuIIPc compound, only Pc-based redox processes were observed due to the redox inactivity of the Cu2+ cation. In-situ spectroelectrochemical (SEC) analyses supported the voltammetric redox behaviors. Additionally, significant spectral and color changes in SEC analyses indicated that these materials can be used in opto-electrochemical applications.

A novel series of hydroxyl-functionalized Schiff bases was synthesized via condensation reactions of 4-morpholinoaniline with various hydroxybenzaldehydes. The resulting Schiff base ligands were subsequently transformed into novel phthalonitrile derivatives through nucleophilic aromatic substitution, employing potassium carbonate in DMF. The structures of all synthesized compounds were elucidated by FT-IR, 1H-NMR, and MALDI-TOF MS analyses. Cholinesterase inhibitory activities were assessed against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Within the Schiff base series, compound MA3-SB showed the most potent AChE inhibition, with an IC50 value of 11.88 nM. In contrast, the phthalonitrile derivative MA3-OFN displayed the strongest BChE inhibitory activity (IC50 = 4.916 nM), suggesting preferential selectivity for the BChE active site. Molecular docking studies supported the in vitro results, revealing strong binding affinities and multiple stabilizing interactions of MA3-SB and MA3-OFN within the enzyme active sites. These findings indicate that Schiff base derivatives preferentially inhibit AChE, whereas phthalonitrile derivatives display enhanced selectivity towards BChE. The observed structure-activity relationships highlight the potential of these compounds as dual or selective cholinesterase inhibitors and provide promising scaffolds for future drug development targeting distinct stages of Alzheimer's disease.

Cadmium (II) is among the most toxic heavy metals that accumulate in aquatic and biological systems, posing serious risks to environmental and public health. Hence, the development of reliable, rapid, and selective analytical strategies for Cd2+ detection remains a critical challenge. In this study, a novel turn-on fluorescent nanosensor based on a naphthalene-derived Fe3O4@Schiff-base hybrid (Fe3O4@NSB) was designed and synthesized for the spectrofluorimetric determination of Cd2+ ions. The hybrid material was thoroughly characterized by FT-IR, XRD, TGA, SEM, and TEM analyses, confirming the successful surface functionalization without structural degradation of the Fe3O4 core. The as-prepared nanosensor exhibits weak native emission due to photo-induced electron transfer (PET) from the π-conjugated ligand framework to the azomethine (C=N) site, which is efficiently suppressed upon Cd2+ coordination. Under optimized conditions (pH 8.0, λex = 270 nm, λem = 308 nm), the system displayed a pronounced fluorescence enhancement proportional to Cd2+ concentration in the range of 1.5–46.0 μM, with a low detection limit of 0.42 μM and excellent precision (RSD = 2.12%). The sensor demonstrated high selectivity toward Cd2+ over a variety of competing metal ions and biomolecules. Real-sample analyses in river and seawater provided recovery values between 94.95% and 104.45%, showing strong agreement with ICP-MS results. Furthermore, a paper-based test strip incorporating Fe3O4@NSB enabled a distinct visual turn-on response toward Cd2+, indicating its potential for on-site environmental monitoring.

Cholinergic neurons and presynaptic indicators of the cholinergic system gradually disappear as a result of neurodegenerative disorders, including Alzheimer's disease (AD), one of the most prevalent causes of dementia. By inhibiting acetylcholinesterase (AChE) and thus reducing the rate of acetylcholine hydrolysis, these effects can be counteracted. Anticholinesterase medications that have reversible inhibitory effects are therefore used to treat neurodegenerative illnesses. This work involved the synthesis of Schiff base compounds (Schiffb.OH/CN) and their cobalt (Schiffb.CoPc) and copper (Schiffb.CuPc) phthalocyanine compounds, as well as spectrophotometric analysis of their in vitro cholinergic enzyme inhibitory potentials. Overall, it was found that, when compared to the other compounds examined, Schiffb.CuPc was the most potent inhibitor. Furthermore, it exhibited statistically comparable results to the positive control, galantamine (26.17 +/- 0.52 mu M). However, at the concentrations examined, it was shown that the compounds exhibited no action against BuChE. The compounds may be selective for AChE, according to this research.

ABSTRACT In this research, we designed phthalocyanine compounds that are thought to be used as potential acetyl/butyrylcholinesterase inhibitors in the treatment of Alzheimer's disease. First, phthalonitrile compound ( PNM‐CN ), which is the precursor compound for phthalocyanines, was synthesized. Then, by cyclotetramerizing this compound, pyridine‐substituted peripheral cobalt ( PNM‐CoPc ), copper ( PNM‐CuPc ), and manganese ( PNM‐MnClPc ) phthalocyanine compounds were synthesized, and their structures were described using mass, NMR (except phthalocyanines), FT‐IR, and UV–Vis (except phthalonitrile) spectroscopic techniques. Investigations were carried out into the new pyridine‐substituted peripheral ( PNM‐Cu/Co/MnClPcs ) phthalocyanines' in vitro inhibitory properties against butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE). With an IC 50 of 5.95 ± 2.12 μM (AChE) and 0.74 ± 0.01 μM (BuChE), PNM‐CuPc showed the most potent inhibitory effect against AChE and BuChE among all compounds.

Novel metallophthalocyanines (6-8) bearing 4-(2-methoxy-5-(((4-morpholinophenyl)imino)methyl)phenoxy) substituents were synthesized and thoroughly characterized. The structures of the key intermediates and final phthalocyanine complexes were confirmed by FT-IR, 1H NMR, and mass spectrometry. The electrochemical properties of the newly synthesized nickel(II) (6), cobalt(II) (7), and copper(II) (8) phthalocyanines were investigated using cyclic voltammetry (CV) and square wave voltammetry (SWV). Among them, the cobalt(II) phthalocyanine (7) exhibited a distinct metal-centered redox process due to the redox-active nature of its central metal ion, while the nickel(II) (6) and copper(II) (8) analogs displayed relatively limited electrochemical activity. All three complexes showed nearly reversible redox behavior, as evidenced by scan rate-dependent peak current changes. Electropolymerization studies revealed that increasing polymer film thickness led to reduced conductivity and diminished peak currents, accompanied by shifts in oxidation potentials. These findings underscore the significant role of the central metal ion and polymer film characteristics in modulating electrochemical performance. The synthesized phthalocyanines (6-8) also demonstrated promising potential for modifying electrode surfaces, offering improved electrical conductivity, enhanced stability, corrosion resistance, and suitability for sensor and protective coating applications.

The presented work describes the synthesis, characterization, and biological effects of three new Schiff base compounds (SOH-F/Cl/Br) and their phthalonitrile derivatives (SCN-F/Cl/Br). The structures of all synthesized compounds were elucidated by NMR, FT-IR, and mass spectroscopic methods. Enzyme results were obtained at the nanomolar level. Cytotoxic activity of novel compounds was evaluated against neuroblastoma (SH-SY5Y) and mouse fibroblast (NIH-3T3) cell lines using MTT. It has been determined that all tested molecules have a powerful cytotoxic effect; IC50 values were under 10 mu M against SH-SY5Y cells. Among all compounds, the lowest IC50 value was observed in SCN-Br (1.798 +/- 0.036 mu M). Moreover, the IC50 concentration of SCN-Br (12.79 +/- 0.33 mu M) in healthy NIH-3T3 cells was significantly higher than in cancerous cells. The activity comparison of the studied six molecules was made with both DFT calculations and molecular docking calculations. Various proteins that are hCA I protein (PDB ID: 2CAB), hCA II protein (PDB ID: 5AML), and SH-SY5Y protein (PDB ID: 7LQZ, 5WIV, and 2F37) were used in molecular docking calculations. After this comparison, ADME/T calculations were used to analyze the molecules to be used as drugs.

Novel Co-II (nANTH-CoPc), Cu-II (nANTH-CuPc), and (MnCl)-Cl-III (nANTH-MnClPc) phthalocyanines were obtained by substituting the 3-(4-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylimino)methyl)phenoxy) Schiff base compound (nANTH-OH) obtained by the acid-catalyzed condensation reaction of 4-aminoantipyrine and 4-hydroxybenzaldehyde at non-peripheral positions. By using various spectroscopic techniques, (NMR, MALDI-TOF, FT-IR, and UV-Vis), the structures of green-colored phthalocyanine compounds and precursor phthalonitrile compounds were identified. The electrochemical responses of cobalt (II) (nANTH-CoPc), cupper (II) (nANTH-CuPc), and manganese (III) (nANTH-MnClPc) phthalocyanines were determined, and their redox responses were analyzed based on the different metal centers. The results indicated that using redox-active Co2+ and Mn3+ cations instead of Cu(2+)enhanced the redox richness of the complexes due to the observation of extra metal-based electron transfer reactions in addition to the Pc-based ones. In-situ spectroelectrochemical analyses of the complexes were used to support the peak assignments of the redox processes and the spectrum and color of the electrogenerated species during the redox reactions. Supported these redox mechanisms. Multi-electron transfer processes and distinct color changes during these processes indicate the possible usage of these complexes in various electrochemical and opto-electrochemical processes. Metalbased electron transfer reactions illustrated different spectral changes than those of the Pc-based ones, and these spectral changes significantly differed the color of the anionic and cationic species.

In this study, axially substituted silicon (IV) phthalocyanine complexes containing pyrimidine-substituted Schiff bases were synthesized and characterized. The Schiff bases (Pyr-1 and Pyr-2) were synthesized through a condensation reaction between pyrimidine derivatives and appropriate aldehydes, followed by their coordination with silicon (IV) to form the corresponding phthalocyanine complexes (Pyr-1-SiPc and Pyr-2-SiPc). The synthesized Schiff bases (Pyr-1 and Pyr-2) and silicon (IV) phthalocyanine derivatives (Pyr-1-SiPc and Pyr-2-SiPc) were subsequently tested in vivo for their inhibitory effect on the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). A substantial number of these compounds exhibited pronounced inhibitory activity against both enzymes. Notably, among the phthalocyanines and their precursor compounds, the most intriguing were identified as submicromolar selective inhibitors of AChE and BChE, with IC50 values of 4.26 mu M and 6.46 mu M, respectively.

In this work, 4-((5,7-dichloro-2-methylquinolin-8-yl)oxy)phthalonitrile (3) and peripherally tetra 5,7-dichloro8-hydroxy-2-methylquinoline substituted zinc(II) (4), nickel(II) (5), copper(II) (6), cobalt(II) (7) and manganese (III)chloride (8) phthalocyanines were prepared for the first time. Electrochemical characterizations of metallophthalocyanines were performed to determine their redox activities and influence of the metal centers and substituent to the redox responses. Peripherally tetra substituted zinc(II) (4), nickel(II) (5) and copper(II) (6) phthalocyanines illustrated very similar redox responses due to the redox inactivity of the Zn2+, Ni2+and Cu2+ central cations. Peripherally tetra substituted cobalt(II) (7) and manganese (III)chloride (8) phthalocyanines gave metal based electron transfer processes in addition to the phthalocyanine based ones. The reduction processes of cobalt(II) phthalocyanine (7) were assigned to [CoIIPc2-]/[CoIPc2-]1-, [CoIPc2-]1-/[CoIPc3-]2- and [CoIPc3-]2-/[CoIPc4-]3-[CoIIPc2-]/[CoIIIPc2-]1+couples and the oxidation processes were assigned to [CoIIPc2-]/ [CoIIIPc2-]1+and [CoIIIPc2-]1+/[CoIIIPc1-]2+couples. For manganese (III) chloride (8), [Cl1--MnIIIPc2-]/[Cl1-- MnIIPc2-]1-, [Cl1--MnIIPc2-]1-/[Cl1--MnIPc2-]2-, [Cl1--MnIPc2-]2-/[Cl1--MnIPc3-]3- and [Cl1--MnIPc3-]3-/[Cl1-- MnIPc4-]4- couples were recorded during the reduction process and [Cl1--MnIIIPc2-]/[Cl1--MnIIIPc1-]1+couple was recorded during the oxidation process. Spectral changes observed during the in-situ spectroelectrochemical measurements supported these redox mechanisms. Multi-electron transfer processes and distinct color changes indicated possible usage of novel phthalocyanines in various electrochemical and opto-electrochemical processes.

The cytotoxic effects of axial disubstituted silicon phthalocyanine (SiPc) and both peripheral and non-peripheral substituted zinc phthalocyanines (ZnPcp/np) were evaluated on neuroblastoma (SH-SY5Y) and mouse fibroblast (NIH-3T3) cell lines utilizing the MTT assay. All evaluated drugs had a pronounced cytotoxic impact on SH-SY5Y cells, with IC50 values much lower than those observed in NIH-3T3 cells, which displayed the highest IC50 values. These results imply that produced phthalocyanines (SiPc, ZnPcp/np) may be effective, specific, and promising therapeutic candidates for the treatment of neuroblastoma. In addition, the activities of these compounds (SiPc, ZnPcp/np) on alpha-glucosidase and hCA I and II isozymes, which were developed as inhibitors in the treatment of diseases such as diabetes, cancer, glaucoma, obesity, and epilepsy, were also determined. The results obtained proved that these compounds (SiPc, ZnPcp/np) were more potent alpha-glucosidase inhibitors than Acarbose (IC50: 4.58 mu M), which was used as a positive control. Molecular docking calculations of dinitrile derivatives (CNp/np), which are precursor molecules for phthalocyanines, and metal complexes (SiPc, ZnPcp/np) were performed on a series of proteins, including hCA I enzyme protein (PDB ID: 2CAB), hCA II enzyme protein (PDB ID: 3DC3), alpha-Gly enzyme protein (PDB ID: 1UAS), and SH-SY5Y cell protein (PDB ID: 3PBL, 7CKZ, and 7LQZ).

In the presented study, a series of methoxylated pyrazoline compounds containing amine (Py1-NH2 and Py2-NH2), tosyl (Py1-Ts and Py2-Ts), and nitrile (Py1-CN and Py2-CN) group were synthesized The structures of these compounds were clarified (by MS, FT-IR, and NMR analysis) through the use of mass spectral (spectrometer), FT-IR (spectrophotometer), and NMR (spectrometer) data. In order to examine the chemical properties of methoxylated pyrazoline derivatives theoretically, calculations were performed on the B3LYP, HF, and M06-2x methods using the 6-31++g(d,p) basis set. In addition, molecular docking calculations were performed to examine the interactions of methoxylated pyrazoline derivatives against cancer proteins. Afterwards, ADME/T was performed to examine the effects of methoxylated pyrazoline derivatives as drugs on human metabolism. According to the Gaussian calculations, the Py1-NH2 molecule is typically more active than other molecules. However, after the molecular docking calculations, the compounds' effects on cancer proteins were examined, and it was discovered that the Py1-NH2 molecule had more activity overall than the others. Following a comprehensive examination of the compounds' interactions with cancer proteins, the ADME properties of the molecules were examined. According to this analysis, it would not be detrimental to use the chemicals as drugs for human metabolism.

In this work, a series of aldehyde‐substituted phthalocyanine compounds (1, 3, and 5) were prepared by the cyclotetramerization of the 4‐(5‐(diethylamino)‐2‐formylphenoxy) phthalonitrile (a) and the corresponding metal salts. Schiff base‐substituted phthalocyanines (2, 4, and 6) were derived from an aldehyde‐substituted phthalocyanine (1, 3, and 5) via the reaction of aldehyde‐substituted phthalocyanines with an amine reagent. The compounds that were obtained were characterized using FT‐IR, 1H {13C} NMR, UV–Vis, and MS spectra (a and 1–6). The inhibitory qualities of synthesized aldehyde and Schiff base‐substituted complexes against the enzymes butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) were assessed. The majority of phthalocyanines exhibited strong enzyme‐inhibiting properties. Out of the six produced phthalocyanines, 3 and 4 displayed the most intriguing profiles as submicromolar selective AChE inhibitors (IC50 = 0.060 μM), whereas 1 demonstrated the most potent BChE inhibitor (IC50 = 0.024 μM). The aggregation studies of CoPcs, CuPcs, and ZnPcs (1–6) were also carried out in this work.

ABSTRACTIn this study, novel chlorine‐thymol derivatives (1,3‐bis(4‐chloro‐2‐isopropyl‐5 methylphenoxy)propan‐2‐ol (Thy‐OHI) and 2‐[2‐(4‐chloro‐2‐isopropyl‐5‐methylphenoxy)ethoxy]ethanol (Thy‐OHII)) and axially di‐4‐chloro‐2‐isopropyl‐5‐methylphenoxy (Thy‐SiPc), 1,3‐bis(4‐chloro‐2‐isopropyl‐5‐methylphenoxy)propanoxy (Thy‐OHI‐SiPc), and 2‐[2‐(4‐chloro‐2‐isopropyl‐5‐methylphenoxy)ethoxy]ethanoxy (Thy‐OHII‐SiPc) substituted silicon phthalocyanine compounds were obtained, and their structures were elucidated by the combination of various methods such as NMR, IR, UV–Vis, and MS. The inhibitory effects of these compounds (Thy‐OHI, Thy‐OHII, Thy‐SiPc, Thy‐OHI‐SiPc and Thy‐OHII‐SiPc), synthesized for the first time, on cholinesterase enzymes (AChE and BChE) were investigated in the laboratory environment. In the studies, notably Thy‐OHI‐Si and thymol derivative ligand Thy‐OHII displayed significant inhibition against AChE and BChE.

Cancer has grown to be a global issue and has put strain on the healthcare system in recent years. Promising alternatives for the treatment of cancer include photodynamic therapy (PDT). For therapeutic purposes, phthalocyanines have been widely employed as sensitizers, especially for photodynamic treatment (PDT). The primary goal of this work is to examine the photophysicochemical properties of newly synthesized and characterized pyrazoline substituted peripherally tetra substituted and non-peripherally tetra substituted ZnIIphthalocyanines. Several techniques were applied during the characterization of the novel compounds, such as mass (MALDI-TOF), nuclear magnetic resonance (NMR), infrared (FT-IR), and UV-Vis spectroscopies. The impact of substituting 3-(5-(4-(dimethylamino)phenyl)-1-phenyl-4,5-dihydro-1H-pyrazole-3-yl)phenol from the peripheral and non-peripheral positions on solubility and aggregation behaviors was examined. The newly synthesized pyrazoline substituted ZnII-phthalocyanines display high solubility in common organic solvents and additionally do not aggregate at concentrations from 1 to 10 mu M. The potential use of the pyrazoline substituted ZnII-phthalocyanines as a photosensitizers in photodynamic therapy was investigated by examining their photophysical and photochemical properties. Non-peripheral pyrazoline substituted ZnII-phthalocyanine (HYZnPcnp) may be a potential photosensitizer for PDT, owing to an examination of the results.

The axially silicon phthalocyanines, consisting of different acyclic hydrocarbons, were generated by SiPcCl 2 reacting with either geraniol or phytol in toluene in the presence of NaH. FT-IR, UV-Vis, MALDI TOF, and NMR spectroscopy all provided information about the structures of silicon phthalocyanines. The cholinesterase, tyrosinase, and alpha-glucosidase inhibitory effects of G-SiPc and P-SiPc were tested using spectrophotometric assays. The IC 50 values of G-SiPc and P-SiPc were 7.22 +/- 0.53 and 11.28 +/- 2.73 mu M for AChE; 70.05 +/- 3.00 and 60.55 +/- 3.80 mu M for BuChE. In addition, G-SiPc and P-SiPc inhibited the tyrosinase enzyme with IC 50 values of 280.36 +/- 7.92 mu M and 40.51 +/- 3.88 mu M, respectively. P-SiPc had about seven times stronger inhibitory properties than G-SiPc . The substances exhibited less inhibition than acarbose in the alpha-glucosidase inhibitory assay. Finally, the cytotoxic effects of G-SiPc and P-SiPc were investigated using the MTT assay on L-929 mouse fibroblast cells as normal cells. G-SiPc and P-SiPc did not reach IC 50 values up to 100 mu M.

The new phthalocyanines, H2Pc (4), ZnPc (5), and PbPc (6) linked to 1,2,4-triazole groups were synthesized and characterized. Additionally, the performance of these compounds in photodynamic therapy was investigated. The new metal-free phthalocyanine (H2Pc) (4) was directly obtained from new phthalonitrile (3) without the addition of any metal salt. This original nitrile compound (3) was converted to several new metallic phthalocyanines (Pcs) such as Zn(II) (5), and Pb(II) (6) using appropriate metal salts. Newly prepared phthalocyanines (4-6) were examined for their photodynamic therapeutic (PDT) properties as photosensitizers (PS), yielding significant findings. The structures of these newly obtained compounds were elucidated using spectroscopic techniques such as MALDI-TOF MS, FT-IR, UV-vis, 1H NMR and 13C NMR.

In this study, new Schiff base compounds (SB-F-OH, SB-Cl-OH and SB-Br-OH) were derived from chalcone-derived amine compounds containing halogen groups and 4-hydroxybenzaldehyde. Also, their phthalonitrile compounds (SB-F-CN, SB-Cl-CN and SB-Br-CN) have been synthesized. The structures of these compounds were elucidated by NMR, FT-IR and Mass spectroscopic methods. The quantum chemical parameters were calculated at B3LYP/6-31++g(d,p), HF/6-31++g(d,p) and M062X/6-31++g(d,p) levels. As the biological application of the synthesized compounds, (i) their inhibition properties of the synthesized compounds on Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) metabolic enzymes were investigated, and their potential anticancer activities against neuroblastoma (NB; SH-SY5Y) and healthy fibroblast (NIH-3T3) cell lines were determined by in vitro assays. All compounds showed inhibition at nanomolar level with the Ki values in the range of 97.86 ± 30.51-516.82 ± 31.42 nM for AChE, 33.21 ± 4.45-78.50 ± 8.91 nM for BChE, respectively. It has been determined that all tested compounds have a remarkable cytotoxic effect against SH-SY5Y, and IC50 values were significantly lower than NIH-3T3 cells. The lowest IC50 value was observed in SB-Cl-OH (7.48 ± 0.86 µM) and SB-Cl-CN (7.31 ± 0.69 µM). The molecular docking of the molecules was also investigated using crystal structure of AChE enzyme protein (PDB ID: 4M0E), crystal structure of BChE protein (PDB ID: 6R6V) and SH-SY5Y cancer protein (PDB ID: 2F3F, 3PBL and 5WIV). The ADME properties of the compounds were investigated. MM/GBSA method is calculated binding free energy. Afterwards, ADME/T analysis was performed to examine the some properties of the molecules.Communicated by Ramaswamy H. Sarma.

Pyrazoline-fused peripheral zinc phthalocyanine (HY-ZnPcP) showed the highest singlet oxygen generation in DMSO, and it is thought to be a photosensitizer candidate for photodynamic therapy.

Different properties of phthalocyanine compounds can be measured both theoretically and experimentally. In this study, tetra substituted phthalocyanines (H2 (2) and CuII (3) were performed using 4-(4-(4-methoxyphenethyl)-3-benzyl-5-oxo-4,5-dihydro-1,2,4 triazol-1-yl)phthalonitrile (1). The structures of all these original compounds synthesized were elucidated using distinctive of spectroscopic techniques.Theoretical comparison of the chemical and biological activities of phthalocyanine molecules and its copper metal complex has been made. Chemical activities were compared with Gaussian software program and biological activities were compared with molecular docking calculations. Used proteins for biological activity are the crystal structure of estrogen receptor protein (from the breast cancer), ID: 1A52, crystal structure of VEGFR kinase protein (from liver cancer), ID: 3WZE, crystal structure of MLK4 kinase (colon cancer) ID: 4UYA, and crystal structure of an allosteric Eya2 phosphatase inhibitor protein (from lung cancer), ID: 5ZMA. After, the interactions between molecules and proteins were determined using the Protein-Ligand Interaction Profiler (PLIP) server.