C60 Derivatives Research Articles

Synthesis of tricyclic 1,4-dihydro-1,4-phosphagermines - trying to establish molecular fencing of reactive centers.

Novel tricyclic 1,4-dihydro-1,4-phosphagermines (3a and 4a) were synthesised from Ge(NR2)2-bridged 1,3-imidazole-2-thione derivative 2a; all structures were crystallographically confirmed. In going from rather small alkyl substituents (Me, nBu) at the nitrogen centers of the 1,3-imidazole-2-thione units to sterically more demanding R = Mes and changing the employed Ge reagent from (R2N)2GeCl2 to R2NGeCl3 we achieved access to mixed functional bis(1,3-imidazole-2-thione)-substituted germanium derivative 2c. The latter was treated with MeLi and, subsequently, with PCl3 to yield a pentacyclic P,Ge-heterocycle (5); its formation was rationalized using DFT theoretical calculations.

Ethynyl-substituted benzosiloxaboroles: the role of C(π)⋯B interactions in their crystal packing and use in Cu(i)-catalyzed 1,3-dipolar cycloaddition.

The synthesis and characterization of two novel 6-ethynyl-7-halogen substituted benzosiloxaboroles (Hal = F, Cl) is reported. The crystal structures of these compounds show a unique type of supramolecular assembly dictated by distinctive C(π)⋯B interactions resulting in the formation of columnar networks involving alternating ethynyl groups and boron atoms. The QTAIM, NBO and NCI analyses were performed in order to obtain a deeper quantitative insight into the nature of these interactions including energy and charge density distribution. The fluoro derivative 1c was used as a starting material in Cu-catalyzed 1,3-dipolar cycloaddition reactions with substituted benzenesulfonyl azides giving rise to benzosiloxaboroles with pendant 1-(arylsulfonyl)-1,2,3-triazole-4-yl functionalities or analogous ionic species, i.e., 1,2,3-triazolium arylsulfonates. Screening of antimicrobial activity of obtained derivatives against a wide selection of Gram-positive and Gram-negative bacteria as well as fungi strains was performed and the obtained results were compared with the data obtained previously for related benzosiloxaborole derivatives.

N-Type Fullerene-Carbon Dots: Synthesis and Electrochemical and Photophysical Properties.

The covalent incorporation of C60 and C70 derivatives of the well-known n-type organic semiconductor PCBM ([6,6]-phenyl-C61-butyric acid methyl ester) onto carbon dots (CD) is described. Morphological and structural characterization reveal combined features of both pristine starting materials (CD and PCBM). Electrochemical investigations evidenced the existence of additional reduction processes to that of CD or PCBM precursors, showing rich electron-acceptor capabilities, with multistep processes in an affordable and narrow electrochemical window (ca. 1.5 V). Electronic communication in the obtained nanoconjugated species were derived from steady-state absorption and emission spectroscopies, which showed bathochromically shifted absorptions and emissions well entering the red region. Finally, the lower fluorescence quantum yield of CD-PCBM nanoconjugates, compared with CD, and the fast decay of the observed emission of CD, support the existence of an electronic communication between both CD and PCBM units in the excited state.

Iodoquinazoline-derived VEGFR-2 and EGFRT790M dual inhibitors: Design, synthesis, molecular docking and anticancer evaluations

Herein, we report the synthesis of a series of new fourteen iodoquinazoline derivatives 7a-c to 13a-e and their evaluation as potential anticancer agents via dual targeting of EGFRT790M and VEGFR-2. The new derivatives were designed according to the target receptors structural requirements. The compounds were evaluated for their cytotoxicity against HepG2, MCF-7, HCT116 and A549 cancer cell lines using MTT assay. Compound 13e showed the highest anticancer activities with IC50 = 5.70, 7.15, 5.76 and 6.50 µM against HepG2, MCF-7, HCT116 and A549 cell lines correspondingly. Compounds 7c, 9b and 13a-d exhibited very good anticancer effects against the tested cancer cell lines. The highly effective six derivatives 7c, 10, 13b, 13c, 13d and 13e were examined against VERO normal cell lines to estimate their cytotoxic capabilities. Our conclusion revealed that compounds 7c, 10, 13b, 13c, 13d and 13e possessed low toxicity against VERO normal cells with IC50 prolonging from 41.66 to 53.99 μM. Also compounds 7a-c to 13a-e were further evaluated for their inhibitory activity against EGFRT790M and VEGFR-2. Also, their ability to bind with both EGFR and VEGFR-2 receptors was examined by molecular modeling. Compounds 13e, 13d, 7c and 13c excellently inhibited VEGFR-2 activity with IC50 = 0.90, 1.00, 1.25 and 1.50 µM respectively. Moreover, Compounds 13e, 7c, 10 and 13d excellently inhibited EGFRT790M activity with IC50 = 0.30, 0.35, 0.45 and 0.47 µM respectively. Finally, our derivatives 7b, 13d and 13e showed good in silico calculated ADMET profile.

Construction of synergistic active sites on MoS2 basal plane by interfacing with C60 derivative for enhanced photocatalytic hydrogen evolution coupled with biomass alcohol conversion

As a promising alternative to platinum, molybdenum disulfide (MoS2) is widely utilized as catalyst/co-catalyst in hydrogen evolution reaction (HER). However, its inactive basal plane greatly hampers its catalytic activity. Herein, we propose a function-oriented strategy to enhance the catalytic activity of MoS2 by interfacing with fullerene derivatives, specifically indene-C60 bisadduct (ICBA). The ICBA-MoS2 hybrid was then employed as an efficient co-catalyst, in conjunction with CdS, to construct a photocatalyst for solar-driven hydrogen production coupled with the selective oxidation of furfural alcohol (FOL) to furfural (FAL). The optimized 5 % ICBA-MoS2/CdS (5 %-IMC) sample exhibits a remarkable H2 and FAL production rates of 978 and 1160 μmol h−1 g−1, respectively, which was 2.4 times higher than that of the primitive sample without ICBA modified. This prominent catalytic performance can be attributed to the high activity of synergistic active sites in ICBA-MoS2, as well as the speed transportation and separation of the photogenerated charges from CdS to ICBA-MoS2, as evidenced by both experimental and theoretical investigations.

Antioxidative activity of alcohol-soluble fullerene derivative

To utilize the radical scavenging property of fullerene (C60), hydrophilic poly(ethylene glycol) (PEG) was chemically attached by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The resulting C60-PEG derivatives were soluble in methanol when the molecular weight of PEG was 5,000. The antioxidative activity was evaluated for the alcohol-soluble C60 derivative. The C60-PEG has sufficient antioxidative activity with the β-carotene-attributed chromaticity of 76% for the C60-PEG derivative (9.96 mM). Further chemical modification will produce water-soluble fullerenes with higher antioxidative activities.

Synthesis of an Open‐Cage C60 Derivative with a Double Stopper

AbstractThe construction of a suitable stopper on a C60 orifice is of importance to prevent the release of once‐encapsulated chemical species. However, a single stopper on a large orifice is in usual not sufficient to retain a small molecule within the C60 cavity. In this work, we introduced a double stopper, constituted of two hydroxy groups, on a huge orifice with a ring‐atom count of 18 by a reduction using BH3⋅THF. The resulting double stopper was demonstrated to effectively isolate an argon atom inside the cavity so that the argon was retained even under mass spectrometric conditions at 200 °C. The structure of the open‐cage C60 derivative with the double stopper was confirmed by X‐ray diffraction analysis, showing a dimeric configuration via intermolecular hydrogen‐bondings. The dimerization behavior was also studied in solution.

Indazole derivatives as novel inhibitors of monoamine oxidase and D-amino acid oxidase

The monoamine oxidase (MAO) enzymes metabolize neurotransmitter amines in the peripheral and central tissues, and inhibitors of these enzymes find application in the treatment of neuropsychiatric and neurodegenerative disorders. Based on reports that the neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole, inhibits the MAO-B isoform, the present study investigated the MAO inhibition potencies of a synthetic series of fifteen C5- and C6-substituted indazole derivatives. While only one derivative (5c) was a submicromolar inhibitor of human MAO-A (IC50 = 0.745 µM), all compounds inhibited human MAO-B with submicromolar IC50 values. Substitution on C5 of indazole yielded particularly potent MAO-B inhibition with IC50 values that ranged from 0.0025–0.024 µM. Further investigation of a selected indazole derivative showed a competitive mode of MAO inhibition. To further explore the pharmacological properties of the indazole derivatives, they were also evaluated as potential inhibitors of porcine D-amino acid oxidase (DAAO). None of the synthetic compounds were noteworthy DAAO inhibitors, however, 1H-indazol-5-ol, a synthetic precursor, was found to be a good potency inhibitor with an IC50 value of 2.03 µM.

Pd-catalyzed synthesis, characterization, and biological evaluations of pyrazole derivatives: DFT, molecular modelling and antioxidant studies

Using Pd(PPh3)4 as a catalyst, a new series of coupling products (5a–5l) synthesized from pyrazole derivatives (4a-4c) and substituted boronic acids. Afterward, 1H, 13C-NMR, FT-IR, UV-visible, and LC-MS techniques were used to characterize the pyrazole derivatives. These pyrazole derivatives (4a-4c and 5a-5l) were assessed for their in-vitro antifungal activity, growth pattern evaluations, and hemolytic assays against the Candida strains. The antibacterial inhibitory potential of the lead compound 5c, with a panel of three Gram-positive bacterial strains and two Gram-negative bacterial strains, was employed to find out MIC, FICI, and toxicity. Results showed that the MIC values with all bacterial strains for compound 5c indicate substantial antimicrobial potential. Analog 5c was tested for its ability to interact with Ct-DNA using various techniques. Compound 5c showed binding constants (Kb) of 9.93 × 105 M−1 while the Gibbs free energy was -34.22 kJmol−1. The linear Stern-Volmer constant (KSV) for 5c was calculated to be 4.81 × 104. DFT calculation study has been investigated for the geometrical optimization and energy parameters calculation. Pyrazole derivative 5c was used for molecular modelling investigation with PDB: 1BNA, 2XCT, and 5FSA, which validated the manner of binding and supported in vitro DNA binding results. Utilizing the DPPH and H2O2 assay, derivative 5c was also tested for antioxidant activity.

The effect of chemically functionalized C60-nanocages as sorbents and sensors for methamphetamine drug: A DFT and QTAIM study

In this study, the sensing capabilities of pristine and doped C60 (R-C60) with elements of O, Al, Ga, Br, Mg, V, Y and Zn toward methamphetamine (MAT) were studied using Density-functional theory (DFT) and quantum theory of atoms in molecules (QTAIM). For this purpose, the geometric structures of C60 derivatives (R-C60) were optimized in the presence and absence of MAT at the level of CAM-B3LYP/6-311 + G(d,p) in the water media. Then the adsorption energy, as well as some chemical properties such as HOMO and LUMO energy levels, energy gap, chemical hardness, sensitivity, recovery time, and dipole moment were determined for (R-)C60 and (R-)C60/MAT complex. Among the studied fullerene derivatives, Zn-C60 showed the highest reactivity with MAT with an adsorption energy of −45.02 kcal/mol. According to the results of this study, Zn-C60 has a strong interaction with MAT, and this nanostructure could be an electroactive sensing material or a significant carrier for this drug.

Targeting carbonic anhydrases II/IX/XII with novel series of coumarin-based compounds: Synthesis, biological activity and molecular dynamics analysis

In the current study, unique series of coumarin sulfonate and sulfamate derivatives were synthesized. Their selectivity and inhibitory activity against glaucoma and cancer-associated CAs (hCA II, IX, and XII) were evaluated compared to standard acetazolamide. In addition, the cytotoxic effects of the synthesized compounds on colorectal carcinoma (HCT116) were examined. Generally, structure-activity relationship (SAR) analysis revealed that potent inhibitors bearing zinc binding group (ZBG) dimethyl sulfamate (4a-c) were shown to lack selectivity against three isoforms owing to the classical inhibitory mode of action. The incorporation of aryl or fluoro aryl sulfone moiety in non-sulfamate coumarin derivatives shifted selectivity toward cancer-related isoforms XII and IX, respectively. Para-fluorine substituted derivative 3c with IC50 value of 0.62 µM exhibited excellent activity and selectivity against hCA IX, while benzene sulfone possessing derivative 3b demonstrated selectivity toward hCA XII with IC50 value of 0.56 µM. Moreover, coumarin derivatives with ethyl sulfone (3e, 3i, and 6a) reported excellent selectivity toward CAII. In-silico studies were also conducted over selective, potent compounds. Molecular docking studies have shown that potent compounds could interact with the active site by different modes of action. The molecular dynamic analysis confirmed the stability of the protein in the presence of a potent ligand.

Design, synthesis, and molecular docking studies of new phenanthrene-linked oxadiazoles as potential antimicrobial agents

Oxadiazoles and phenanthrene-based tylophorine alkaloids exhibit diverse biological activities, and the combination of both provides significant biological activity. Herein, we report the novel synthesis of phenanthrene-linked oxadiazoles (7a-m). Molecular docking studies were performed, and the binding energy values with the protein β-ketoacyl-acyl carrier protein synthase III (FabH) enzyme provide an attractive new target for the development of antibacterial agents and support their biological activities. Most of the derived compounds adhere to "Lipinski's Rule of Five" for assessing drug-likeness. The newly synthesized analogues were assessed for their in vitro antibacterial and antifungal activities against selected gram-positive and gram-negative bacteria as well as fungal strains. Compounds 7b, 7e, 7j, and 7c demonstrate potential antimicrobial activity, while the remaining compounds show moderate activity. The selected derivatives (7b, 7e, 7j, and 7c) exhibit a promising zone of inhibition (mm) against the minimum inhibitory concentration.

1,2,3-Triazole-based esters and carboxylic acids as nonclassical carbonic anhydrase inhibitors capable of cathepsin B inhibition.

Herein, we report the design and synthesis of a library of 28 new 1,2,3-triazole derivatives bearing carboxylic acid and ester moieties as dual inhibitors of carbonic anhydrase (CA) and cathepsin B enzymes. The synthesised compounds were assayed in vitro for their inhibition potential against four human CA (hCA) isoforms, I, II, IX and XII. The carboxylic acid derivatives displayed low micromolar inhibition against hCA II, IX and XII in contrast to the ester derivatives. Most of the target compounds showed poor inhibition against the hCA I isoform. 4-Fluorophenyl appended carboxylic acid derivative 6c was found to be the most potent inhibitor of hCA IX and hCA XII with a KI value of 0.7 μM for both the isoforms. The newly synthesised compounds showed dual inhibition towards CA as well as cathepsin B. The ester derivatives exhibited higher % inhibition at 10-7 M concentration as compared with the corresponding carboxylic acid derivatives against cathepsin B. The results from in silico studies of the target compounds with the active site of cathepsin B were found in good correlation with the in vitro results. Moreover, two compounds, 5i and 6c, showed cytotoxic activity against A549 lung cancer cells, with IC50 values lower than 100 μM.

The Second Derivative of Fullerene C60 (SD-C60) and Biomolecular Machinery of Hydrogen Bonds: Water-Based Nanomedicine.

The human body contains 60-70% water, depending on age. As a body fluid, it is not only a medium in which physical and chemical processes take place, but it is also one of the active mediators. Water is the richest substance with non-covalent hydrogen bonds. Water molecules, by themselves (in vacuum), are diamagnetic but when organized into clusters, they become diamagnetic or paramagnetic. Also, biomolecules (DNA, collagen, clathrin, and other proteins) have non-covalent hydrogen bonds in their structure. The interaction, as well as signal transmission, between water and biomolecules is achieved through the vibrations of covalent and non-covalent hydrogen bonds, which determine the state and dynamics of conformational changes in biomolecules. Disruptive conformational changes in biomolecules, cells, and tissues lead to their dysfunctionality, so they are a frequent cause of many disorders and diseases. For example, the rearrangement of hydrogen bonding due to mitochondrial disease mutation in cytochrome bc1 disturbs heme bH redox potential and spin state. In order to prevent and repair the dysfunctional conformational changes, a liquid substance was developed based on the second derivative of the C60 molecule (SD-C60), which has classical and quantum properties. The characterization of SD-C60 by UV-VIS-NIR, FTIR, TEM, and AFM/MFM was performed and it is shown that SD-C60 water layers generate vibrations with near-zero phase dispersion which are transmitted through Fibonacci's water chains to biomolecules. In comparison with previously published SD-C60 derivate (3HFWC, size until 10 nm, and 1-5 water layers), the improved formulation (3HFWC-W, size 10-25 nm, and 6-9 water layers) showed multiplied cytotoxic activity against melanoma cell lines of different aggressiveness. Apart from this, the mode of action was preserved and based on an induction of senescence rather than cell death. Importantly, high selectivity towards malignant phenotypes was detected. Observed effects can be ascribed to a machinery of hydrogen bonds, which are generated in SD-C60 and transmitted through water to biomolecules. This approach may open a new field in science and healthcare-a "water-based nanomedicine".

New Chromone-Thiazolopyrimidine Hybrids as Potent TNF-α, IL-6 and PGE2 Inhibitors: Synthesis, Anti-Inflammatory Evaluation and Molecular Modeling Studies

Inflammation is deemed to be a substantial and terrifying indicator of the advancement of diverse life‐threatening diseases. Regarding the preceding studies that assured the remarkable efficiency of chromone scaffolds and thiazolopyrimidine-based compounds as efficacious anti-inflammatory candidates, a new chromone-thiazolopyrimidine hybrid 3a–t was synthesized and investigated for their in vivo anti-inflammatory efficacy as well as their ulcerogenic effect. The majority of the examined candidates displayed a noticeable anti-inflammatory potency comparable to the standard drug (celecoxib), and interestingly, they exhibited no ulcerogenic effect. Moreover, the promising compounds 3a, 3c, 3i, and 3 l were assessed for their inhibitory properties against the production of various inflammatory mediators (TNF-α, IL-6, and PGE2). They demonstrated a noteworthy suppression efficiency on the emission of TNF-α, IL-6 and PGE2 (TNF-α level range 52.30-63.56 pg/mL, IL-6 level range 165.44–177.17 pg/mL, PGE2 level range 38.46–47.21 pg/mL) relative to celecoxib (49.77, 164.49, and 37.50 pg/mL, respectively). Additionally, the molecular docking studies for the bioactive derivatives 3a, 3c, 3i, and 3l were accomplished to determine the interaction forms inside the binding sites of the inflammatory mediators TNF-α, IL-6, and mPGES-1. The screened receptors exhibited essential binding interactions with the chromone and the 3-oxothiazolo[3,2-a]pyrimidine scaffolds. Finally, ADME investigations of the latter derivatives portended their significant oral bioavailability and GI absorption.

Vetting of New 2,5-Bis (2,2,2-trifluoroethoxy) Phenyl-Linked 1,3-Thiazolidine-4-one Derivatives as AURKA and VEGFR-2 Inhibitor Antiglioma Agents Assisted with In Vitro and In Silico Studies.

The bioactivity of 1,3-thiazolidin-4-one derivatives with a 2,5-bis (2,2,2-trifluoroethoxy) phenyl moiety was computationally developed and evaluated. All of the synthesized thiazolidin-4-one derivatives have their chemical structures characterized using a variety of methods, including nuclear magnetic resonance (NMR) (1H and 13C), high-resolution mass spectrometry (HRMS), and Fourier transform infrared (FTIR) radiation. A human glioblastoma cancer cell line (LN229) was used to investigate the purified derivatives' antiglioma cancer efficacy. By using the MTT, colony formation, and tunnel tests, respectively, the in vitro cytotoxic and apoptotic effects of these compounds were assessed. Thiazolidin-4-one derivatives 5b, 5c, and 5e were discovered to have the best efficacy against glioblastoma cells out of all of these compounds. The derivatives 5b, 5c, and 5e were determined to have respective IC50 values of 9.48, 12.16, and 6.43 g/mL. Computation results showed that the bioactivity evaluations of the compounds were quite significant. The bridging -NH group forms a hydrogen bond with Glu 260 of synthesized derivatives 5b, 5c, 5d, 5e, and 5h. The vast majority of freshly developed compounds obeyed Lipinski's rule of five, which is in line with the results that the ADMET model predicted. Additionally, molecular docking evaluation and molecular dynamics simulation investigations against the proteins AURKA and VEGFR-2 were conducted for the synthesized compounds to incorporate both in silico and in vitro data. The findings revealed that almost all of the compounds had considerable binding to AURKA and VEGFR-2 residues, with binding affinities ranging from -9.8 to -7.9 kcal/mol. Consequently, the results of the biological investigations and the docking scores demonstrated that thiazolidinone molecule 5e containing 4-chlorophenyl substituent may be considered as a potential moiety for glioblastoma cancer treatments.

Design, synthesis, and antimicrobial evaluation of new antipyrine derivatives bearing thiazolopyridazine and pyrazolothiazole scaffolds

In the current research, a new set of antipyrine–thiazole hybrids were designed and synthesized and screened for their antimicrobial activities against Gram-positive and Gram-negative bacteria and fungal strains using ciprofloxacin and nystatin as reference drugs. The antipyrine derivatives 3a, 5a, 7c, and 11a revealed promising and broad antibacterial activity especially against S. aureus, followed by in vitro enzyme inhibitory assay against S. aureus DNA gyrase to predict the mechanism of action. The thiazole 3a and pyrazolo[4,3-d]thiazole 7c afforded superior inhibitory activity against S. aureus DNA gyrase (IC50 = 0.292 ± 0.15 and 0.255 ± 0.10 µM, respectively) in comparison with ciprofloxacin (IC50 = 0.331 ± 0.20 µM). Finally, the in silico molecular docking and ADME studies were established to give better rationalization and optimization of efficient new antimicrobial leads.

Inhibitory Effects of B-, C-, and E-Ring-Truncated Deguelin Derivatives Against A549, HCT116, and MCF-7 Cancer Cells.

Deguelin has been extensively studied for its anticancer properties; however, its clinical application has been hindered by concerns about in vivo toxicity. Structural modifications of deguelin including ring truncation have been explored to enhance its pharmacological properties. In this study, the design and straightforward synthesis of a series of B, C, and E (BCE)-ring-truncated deguelin analogues with deoxybenzoin backbone were described. The structure-activity relationships (SARs) were established by evaluation of their inhibitory activities against three cancer cell lines, A549 (adenocarcinomic human alveolar basal epithelial cells), HCT116 (human colorectal cancer cells), and MCF-7 (breast cancer cells). Six derivatives demonstrated significant and selective inhibitory activities. The ketone derivative 3a showed potency against A549 (IC50 = 6.62 μM) while the oxime analogue 6a and D-ring-benzylated ketone analogue 8d exhibited activity against HCT116 (IC50 = 3.43 and 6.96 μM, respectively). Moreover, the D-ring alkylated derivatives 8c and 8e-f were active against MCF-7 cells (IC50 < 10 μM). The potential suitability of the BCE-ring-truncated deguelin derivatives for drug development was further supported by the favorable in silico prediction of their physicochemical properties, druglikeness, and toxicity. This study could provide valuable insights for the further development of novel anticancer agents.

Structure and antiradical activity of N-monosubstituted amino acid derivatives of fullerene C60 in aqueous colloidal solutions

The dimensional characteristics of nanoparticles of N-mono- substituted amino acid derivatives of fullerene C60 (AAFDs) in aqueous colloidal solutions, determined by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS), were compared. The DLS data on the dimensional characteristics of fullerene C60 and AAFD nanoparticles, obtained at scattering angles of 90° and 173°, are close in values with a correlation coefficient of 0.89, and the SAXS data indicate that AAFDs form ordered structures in solution. Based on the results of DLS and the ability of fullerene and AAFDs to inhibit peroxyl radicals, it can be concluded that varying the concentrations of the studied compounds in the range from 10-7 to 10-3 m does not affect the degree of aggregation of their nanoparticles.

Benzimidazoles Containing Piperazine Skeleton at C-2 Position as Promising Tubulin Modulators with Anthelmintic and Antineoplastic Activity.

Benzimidazole anthelmintic drugs hold promise for repurposing as cancer treatments due to their interference with tubulin polymerization and depolymerization, manifesting anticancer properties. We explored the potential of benzimidazole compounds with a piperazine fragment at C-2 as tubulin-targeting agents. In particular, we assessed their anthelmintic activity against isolated Trichinella spiralis muscle larvae and their effects on glioblastoma (U-87 MG) and breast cancer (MDA-MB-231) cell lines. Compound 7c demonstrated exceptional anthelmintic efficacy, achieving a 92.7% reduction in parasite activity at 100 μg/mL after 48 hours. In vitro cytotoxicity analysis of MDA-MB 231 and U87 MG cell lines showed that derivatives 7b, 7d, and 7c displayed lower IC50 values compared to albendazole (ABZ), the control. These piperazine benzimidazoles effectively reduced cell migration in both cell lines, with compound 7c exhibiting the most significant reduction, making it a promising candidate for further study. The binding mode of the most promising compound 7c, was determined using the induced fit docking-molecular dynamics (IFD-MD) approach. Regular docking and IFD were also employed for comparison. The IFD-MD analysis revealed that 7c binds to tubulin in a unique binding cavity near that of ABZ, but the benzimidazole ring was fitted much deeper into the binding pocket. Finally, the absolute free energy of perturbation technique was applied to evaluate the 7c binding affinity, further confirming the observed binding mode.