Synthesis and investigation of cytotoxicity of new N- and S,S-substituted-1,4-naphthoquinone (1,4-NQ) derivatives on selected cancer lines

1,4-Naphthoquinones (1,4-NQ) have been reported to possess a variety of pharma-cological properties including antibacterial, antifungal, antiviral, anti-inflammatory, anti-artherosclerotic, and anticancer effects. In this study, new N- and S,S-substituted-1,4-NQ derivatives were synthesized in excellent yields and were completely characterized by spectroscopic analysis IR, NMR (¹H and ¹³C), MS and microanalysis. The cytotoxic activities of 1,4-NQ derivatives were examined against to A-549, DU145, HCT-116 and MDA-MB-231 cancer cells. Among these compounds, 2-[4-(2-furoyl)piperazine-1-yl]-3-chloro-1,4-NQ 5 and 2,3-bis(cyclobuthylsulfanyl)-1,4-NQ 17 were identified as the most potent anticancer agents with cytotoxic activity against three cell lines (breast (MDA-MB-231), prostate (DU145), colorectal (HCT-116).     

Synthesis,cytotoxicity, apoptosis and molecular docking studies of novel phenylbutyrate derivatives as potential anticancer agents

Phenylbutyrate (PB), a small aromatic fatty acid, has been known as an interesting compound with the ability of anti-proliferation and cell growth inhibition in cancer cells. In the present study, a series of PB derivatives were synthesized by Passerini multicomponent reaction and their cytotoxic activities against various human cancer cell lines including A549 (non-small cell lung cancer), MDA-MB-231 (breast cancer), and SW1116 (colon cancer) were evaluated. The results revealed that B9, displayed significantly higher in vitro cytotoxicity with IC₅₀ of 6.65, 8.44 and 24.71 μM, against A549, MDA-MB-231 and, SW1116, respectively, in comparison to PB. The effects of these compounds on the proliferation of MCF-10A as non-tumoral breast cell line, showed good selectivity of the compounds between tumorigenic and non-tumorigenic cell lines. Moreover, B9 has indicated apoptosis-inducing activities to MDA-MB-231 cancer cell line in a dose-dependent manner. The molecular docking studies of the synthesized compounds on pyruvate dehydrogenase kinase 2 (PDK2; PDB ID: 2BU8) and histone deacetylase complex (HDAC; PDB ID: 1C3R), as the main targets of PB were applied to predict the binding sites and binding orientation of the compounds to these targets.     

Design,Synthesis, and Antitumor Activity of a Series of Novel 4-(Aromatic Sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-ones

Many sulfonamides show anticancer activity. Based on benzenesulfonylazaspirodienone (HL-X9) identified in our previous work, we optimized the lead compound for better efficacy, thereby synthesizing a series of novel 4-(aromatic sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-one derivatives through a key step of metal-catalyzed cascade cyclization. The preliminary antiproliferative tests have shown that the anticancer activities of acetyl-protected mannose-linked sulfonylazaspirodienone derivatives (7i–7l) have been greatly improved. Among them, 7j is the most potent derivative, with IC₅₀ values of 0.17 µM, 0.05 µM, and 0.07 µM for A549, MDA-MB-231, and HeLa cell lines, respectively. Flow cytometry analysis shows that 7j arrests MDA-MB-231 cells in the G2/M phase and has a certain effect on the apoptosis of MDA-MB-231 cells. In addition, the acute toxicity of 7j was lower than that of adriamycin.     

Cytotoxicity and anticancer activity of natural rubber latex particles for cancer cells

To broaden the knowledge of cytotoxicity of natural rubber latex (NRL) nanoparticles we for the first time examined the latex biocompatibility in vitro against a panel of cancer cells (A549, A2780, and MDA-MB-231). Owing to fractionation of NRL nanoparticles by ultra-centrifuge, the effect of the non-rubber constituents (intermediate of 5.8 wt% and sediment of 0.2 wt%) on the cytotoxicity was clarified. For intermediate constituent, the half maximal inhibitory concentration (IC₅₀) values at 24 h was 1.05 mg/mL for A549 cells, which was one order of magnitude higher in toxicity as compared to that for A2780 (0.24 mg/mL) and MDA-MB-231 (0.36 mg/mL) cells. In addition, profound studies including cell cycle arrest abilities and apoptosis induction profiles against cancer cells were discussed in detail. It was found that the constituents exhibit some significant effect on the cell cycle arrest and trigger apoptosis for A2780 cells. This effective apoptosis induction profiles was more prominent in MDA-MB-231 cells incubated with NRL nanoparticles and sediment loading conditions. The percentage of apoptotic cells was ca. 6–8% of the total cells.     

Kadsufolins A – D and Related Cytotoxic Lignans from Kadsura oblongifolia

Kadsufolins A–D ( 1 – 4 , resp.), four new dibenzocyclooctane‐type lignans, were isolated from the roots and stems of Kadsura oblongifolia, together with eleven known lignans. Their structures and configurations were elucidated by spectroscopic methods including 2D‐NMR techniques. The compounds were also evaluated for cytotoxic activity against human tumor cell lines A549 (lung carcinoma), DU145 (prostate carcinoma), KB (epidermoid carcinoma of the nasopharynx), and HCT‐8 (ileocecal carcinoma). Kadsufolin A ( 1 ), kadsufolin D ( 4 ), angeloylbinankadsurin A, and heteroclitin B were found to show cytotoxic activities against A549, DU145, KB and HCT‐8 with GI₅₀ values of 5.1–20.0 μg/ml.     

Impaired Expression of Cytoplasmic Actins Leads to Chromosomal Instability of MDA-MB-231 Basal-Like Mammary Gland Cancer Cell Line

We have shown previously that two cytoplasmic actin isoforms play different roles in neoplastic cell transformation. Namely, β-cytoplasmic actin acts as a tumor suppressor, whereas γ-cytoplasmic actin enhances malignant features of tumor cells. The distinct participation of each cytoplasmic actin in the cell cycle driving was also observed. The goal of this study was to describe the diverse roles of cytoplasmic actins in the progression of chromosomal instability of MDA-MB-231 basal-like human carcinoma cell line. We performed traditional methods of chromosome visualization, as well as 3D-IF microscopy and western blotting for CENP-A detection/quantification, to investigate chromosome morphology. Downregulation of cytoplasmic actin isoforms alters the phenotype and karyotype of MDA-MB-231 breast cancer cells. Moreover, β-actin depletion leads to the progression of chromosomal instability with endoreduplication and aneuploidy increase. On the contrary, γ-actin downregulation results not only in reduced percentage of mitotic carcinoma cells, but leads to chromosome stability, reduced polyploidy, and aneuploidy.     

Synthesis,in vitro cytotoxicity,and molecular docking study of novel 3,4-dihydroisoquinolin-1(2H)-one based piperlongumine analogues

With the aim of expanding the scope of SAR on piperlongumine (PL), a naturally occurring anticancer molecule, we have designed a novel hybrid molecule bearing 3,4-dihydroisoquinolin-1(2H)-one and trans-cinnamic acids. The structure, based on hybridization strategy, is used for hybridization of naturally occurring scaffolds. We have synthesized 14 hybrid molecules by coupling 3,4-dihydroisoquinolin-1(2H)-one core with cinnamic acids using the mix anhydride approach. The newly synthesized inhibitors were evaluated for cell viability against breast cancer MCF-7 and cervical cancer HeLa cell lines. Furthermore, the active compounds were screened for their potential in breast cancer MDA-MB-231, cervical cancer C33A cell lines, prostate cancer DU-145, PC-3, and normal VERO cells. From the series, compound 10g was seen to inhibit MCF-7 cell growth significantly with GI₅₀ < 0.1 μM along with growth inhibition in MDA-MB-231 (GI₅₀ = 20 μM) and C33A (GI₅₀ = 3.2 μM). While the inhibitor 10i inhibits MCF-7 breast cancer cell growth GI₅₀ = 3.42 μM along with inhibition of cell growth in MDA-MB-231 (GI₅₀ = 30 μM), HeLa (GI₅₀ = 7.67 μM), C33A (GI₅₀ = 13 μM), DU-145 (GI₅₀ = 6.45 μM), PC-3 (GI₅₀ = 8.68 μM), and VERO (GI₅₀ = 2.93 μM), respectively. Furthermore, molecular docking study demonstrated these compounds could bind tightly to the colchicine domain of tubulin through a network of favorable steric and electrostatic interactions and thus act as a tubulin polymerization inhibitor.     

Synthesis and antitumor activities of novel 1,4-substituted phthalazine derivatives

<正>A series of 1,4-substituted phthalazine derivatives were designed and synthesized.All the prepared compounds were screened for their cytotoxic activities against A549.HT-29 and MDA-MB-231 cell lines in vitro.Among them,compounds 7a-7h showed excellent selectivity for MDA-MB-231 cell line with IC_(50) values from 1 nmol/L to 0.92μmol/L.A preliminary SAR study of these derivatives was performed.     

Fucoxanthin Holds Potential to Become a Drug Adjuvant in Breast Cancer Treatment: Evidence from 2D and 3D Cell Cultures

Fucoxanthin (Fx) is a carotenoid derived from marine organisms that exhibits anticancer activities. However, its role as a potential drug adjuvant in breast cancer (BC) treatment is still poorly explored. Firstly, this study investigated the cytotoxic effects of Fx alone and combined with doxorubicin (Dox) and cisplatin (Cis) on a panel of 2D-cultured BC cell lines (MCF7, SKBR3 and MDA-MB-231) and one non-tumoral cell line (MCF12A). Fucoxanthin induced cytotoxicity against all the cell lines and potentiated Dox cytotoxic effects towards the SKBR3 and MDA-MB-231 cells. The combination triggering the highest cytotoxicity (Fx 10 µM + Dox 1 µM in MDA-MB-231) additionally showed significant induction of cell death and genotoxic effects, relative to control. In sequence, the same combination was tested on 3D cultures using a multi-endpoint approach involving bioactivity assays and microscopy techniques. Similar to 2D cultures, the combination of Fx and Dox showed higher cytotoxic effects on 3D cultures compared to the isolated compounds. Furthermore, this combination increased the number of apoptotic cells, decreased cell proliferation, and caused structural and ultrastructural damages on the 3D models. Overall, our findings suggest Fx has potential to become an adjuvant for Dox chemotherapy regimens in BC treatment.     

Synthesis of Novel Methyl 3-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates and Antitumor Activity Evaluation: Studies In Vitro and In Ovo Grafts of Chick Chorioallantoic Membrane (CAM) with a Triple Negative Breast Cancer Cell Line

A series of novel functionalized methyl 3-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates 2a–2h were synthesized by C-C Pd-catalyzed Suzuki-Miyaura cross-coupling of methyl 3-bromothieno[3,2-b]pyridine-2-carboxylate with (hetero)aryl pinacol boranes, trifluoro potassium boronate salts or boronic acids. Their antitumoral potential was evaluated in two triple negative breast cancer (TNBC) cell lines—MDA-MB-231 and MDA-MB-468, by sulforhodamine B assay. Their effects on the non-tumorigenic MCF-12A cells were also evaluated. The results demonstrated that three compounds caused growth inhibition in both TNBC cell lines, with little or no effect against the non-tumorigenic cells. The most promising compound was further studied concerning possible effects on cell viability (by trypan blue exclusion assay), cell proliferation (by bromodeoxyuridine assay) and cell cycle profile (by flow cytometry). The results demonstrated that the GI₅₀ concentration of compound 2e (13 μM) caused a decreased in MDA-MB-231 cell number, which was correlated with a decreased in the % of proliferating cells. Moreover, this compound increased G0/G1 phase and decreased S phases, when compared to control cells (although was not statistic significant). Interestingly, compound 2e also reduced tumor size using an in ovo CAM (chick chorioallantoic membrane) model. This work highlights the potential antitumor effect of a novel methyl 3-arylthieno[3,2-b]pyridine-2-carboxylate derivative.     

Synthesis and in vitro cytotoxic evaluation of 2-hydrazinylpyrido[2,3-b]pyrazin-3(4H)-one derivatives

A series of novel 2-hydrazinylpyrido[2,3-b]pyrazin-3（4H）-one derivatives were synthesized and evaluated for their cytotoxic activities against A549,MDA-MB-231 and HT-29 cell lines in vitro.Pharmacological data indicated that compounds 5b,5c,10a and 10g possessed marked cytotoxicity,especially 10a(with IC₅₀ values of 0.81,2.56 and 1.63μmol/L against A549,MDA-MB- 23 1 and HT29 cell lines,respectively),which had emerged as a lead compound.     

Synthesis and antiproliferative evaluation of 2,3-diarylquinoline derivatives

A number of 2,3-diarylquinoline derivatives were synthesized and evaluated for antiproliferative activities against the growth of six cancer cell lines including human hepatocellular carcinoma (Hep G2 and Hep 3B), non-small cell lung cancer (A549 and H1299), and breast cancer (MCF-7 and MDA-MB-231) cell lines. The preliminary results indicated that 6-fluoro-2,3-bis{4-[2-(piperidin-1-yl)ethoxy]phenyl}quinoline (16b) was one of the most active compounds against the growth of Hep 3B, H1299, and MDA-MB-231 with a GI(50) value of 0.71, 1.46, and 0.72 μM respectively which was more active than tamoxifen. Further investigations have shown that 16b induced cell cycle arrest at G2/M phase followed by DNA fragmentation via an increase in the protein expression of Bad, Bax and decrease in Bcl-2, and PARP which consequently cause cell death.     

Assessment of antioxidant and cytotoxic potential of silver nanoparticles synthesized from root extract of Reynoutria japonica Houtt

Free radicals, mostly consist of reactive oxygen species, are generated in human body by several exogenous and endogenous systems. Overproduction of free radicals is known to cause several degenerative disorders including cancer. The aim of this study is to synthesize silver nanoparticles (AgNPs) using root extract of Reynoutria japonica and to investigate its antioxidant and cytotoxic potential. AgNPs were synthesized by green approach and subsequently characterized using UV–vis spectroscopy, SEM, TEM, FTIR, XRD, EDS and DLS. The antioxidant activity was investigated using DPPH, FRAP, H₂O₂, and ABT?⁺ radical scavenging assays while the cytotoxic effect was assessed using different human cancer cell lines including lung (A549), liver (Hep-G2) and breast (MDA-MB-231) by MTS assay. Moreover, the specificity of NPs was assessed against two normal human cell lines e.g. alveolar and renal primary epithelial cells (HPAEpiC and HRPTEpiC). The UV–vis spectra confirmed the synthesis of AgNPs by producing a characteristic peak at 410 nm. Further analysis confirmed that AgNPs were crystalline in nature, predominantly spherical in shape, with an average width and area of 17.34 nm and 164.46 nm², respectively. DLS analysis revealed that NPs possess a high negative zeta potential value (?28.5 mV), thus facilitating its electrostatic stabilization. AgNPs showed dose dependent antioxidant activity against DPPH, FRAP, H₂O₂ and ABTS with IC₅₀ values 19.25, 22.45, 24.20 and 18.88 µg/ml, respectively. The AgNPs depicted significant cytotoxic effects against A549, Hep-G2 and MDA-MB-231 cell lines with IC₅₀ values of 4.5, 5.1 and 3.46 µg/ml, respectively. Moreover, the NPs exhibited highest selectivity index (>2.0) for A549, Hep-G2 and MDA-MB-231, confirming its specificity towards cancer cell lines. In conclusion, AgNPs prepared from root extract of R. japonica possess strong antioxidant and cytotoxic potential which suggests that they should be investigated further in order to develop safe and effective antioxidant and/or cytotoxic formulations.     

Polyphenol-Enriched Blueberry Preparation Controls Breast Cancer Stem Cells by Targeting FOXO1 and miR-145

Scientific evidence supports the early deregulation of epigenetic profiles during breast carcinogenesis. Research shows that cellular transformation, carcinogenesis, and stemness maintenance are regulated by epigenetic-specific changes that involve microRNAs (miRNAs). Dietary bioactive compounds such as blueberry polyphenols may modulate susceptibility to breast cancer by the modulation of CSC survival and self-renewal pathways through the epigenetic mechanism, including the regulation of miRNA expression. Therefore, the current study aimed to assay the effect of polyphenol enriched blueberry preparation (PEBP) or non-fermented blueberry juice (NBJ) on the modulation of miRNA signature and the target proteins associated with different clinical-pathological characteristics of breast cancer such as stemness, invasion, and chemoresistance using breast cancer cell lines. To this end, 4T1 and MB-MDM-231 cell lines were exposed to NBJ or PEBP for 24 h. miRNA profiling was performed in breast cancer cell cultures, and RT-qPCR was undertaken to assay the expression of target miRNA. The expression of target proteins was examined by Western blotting. Profiling of miRNA revealed that several miRNAs associated with different clinical-pathological characteristics were differentially expressed in cells treated with PEBP. The validation study showed significant downregulation of oncogenic miR-210 expression in both 4T1 and MDA-MB-231 cells exposed to PEBP. In addition, expression of tumor suppressor miR-145 was significantly increased in both cell lines treated with PEBP. Western blot analysis showed a significant increase in the relative expression of FOXO1 in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Furthermore, a significant decrease was observed in the relative expression of N-RAS in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Our data indicate a potential chemoprevention role of PEBP through the modulation of miRNA expression, particularly miR-210 and miR-145, and protection against breast cancer development and progression. Thus, PEBP may represent a source for novel chemopreventative agents against breast cancer.     

Synthesis,characterization, in vitro antimicrobial and cytotoxic evaluation of Co(II), Ni(II), Cu(II) and Zn(II) complexes derived from bidentate hydrazones

Co(II), Ni(II), Cu(II) and Zn(II) complexes have been synthesized from hydrazone ligands (HL¹–HL⁴) obtained by condensation reaction of 6-chlorothiochroman-4-one with benz hydrazide/nicotinic hydrazide/isonicotinic hydrazide/p-toluic hydrazide. The synthesized compounds (1–20) were characterized by physicochemical procedures, i.e. (FTIR, ¹H NMR, ¹³C NMR, mass, ESR, UV–Vis), TGA/DTA, powder XRD, elemental analysis (CHN), magnetic susceptibility and molar conductance measurements. The various data suggested bidentate nature (NO) of hydrazones, which coordinate with central metal ions via nitrogen of azomethine (–C=N–) group and deprotonated carbonyl oxygen in the enolized form, resulting in octahedral complexes. Low values of molar conductance suggested their non-electrolytic nature. Thermal decomposition pattern of complexes confirms the metal oxides as end product. In vitro antimicrobial activity of hydrazones and their metal complexes were evaluated against two gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus); two gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli); and two fungal strains (Candida albicans and Aspergillus niger) by serial dilution method, and it was found that the metal complexes were highly active as compared to hydrazones. Among all the compounds, complexes 11, 13, 14 and 19 were found most efficient antimicrobial agent. The anticancer activity of (1–20) compounds was performed on human cancer cell lines A549 (lung), DU145 (prostate) and SW620 (colorectal) by MTT assay using paclitaxel as reference drug. The cytotoxicity results suggested compounds [Cu(L²)₂(H₂O)₂] 11 as most potent against A549, DU145 and SW620 cancer cell lines with IC₅₀ values of 3.46, 18.21 and 7.61 µM. Furthermore, compounds (9, 10, 11, 12) were also investigated on A549 cell line for their ROS generation and mitochondrial membrane potential loss and suggested that complex [Cu(L²)₂(H₂O)₂] 11 has highest ROS production and induction of apoptosis by mitochondrial depolarization in cancer cells.

Graphic abstract

The synthesized compounds (1–20) were screened for in vitro cytotoxicity against A549 (lung), DU145 (prostate), SW620 (colorectal) human cancer cell lines. Copper complex (11) was found to be the most active antitumor agent which enhance ROS production and MMP loss on A549 cells.

     

Design and Synthesis of Non-Covalent Imidazo[1,2-a]quinoxaline-Based Inhibitors of EGFR and Their Anti-Cancer Assessment

A series of 30 non-covalent imidazo[1,2-a]quinoxaline-based inhibitors of epidermal growth factor receptor (EGFR) were designed and synthesized. EGFR inhibitory assessment (against wild type) data of compounds revealed 6b, 7h, 7j, 9a and 9c as potent EGFR^WT inhibitors with IC₅₀ values of 211.22, 222.21, 193.18, 223.32 and 221.53 nM, respectively, which were comparable to erlotinib (221.03 nM), a positive control. Furthermore, compounds exhibited excellent antiproliferative activity when tested against cancer cell lines harboring EGFR^WT; A549, a non-small cell lung cancer (NSCLC), HCT-116 (colon), MDA-MB-231 (breast) and gefitinib-resistant NSCLC cell line H1975 harboring EGFR^L858R/T790M. In particular, compound 6b demonstrated significant inhibitory potential against gefitinib-resistant H1975 cells (IC₅₀ = 3.65 μM) as compared to gefitinib (IC₅₀ > 20 μM). Moreover, molecular docking disclosed the binding mode of the 6b to the domain of EGFR (wild type and mutant type), indicating the basis of inhibition. Furthermore, its effects on redox modulation, mitochondrial membrane potential, cell cycle analysis and cell death mode in A549 lung cancer cells were also reported.     

Coumarin Sulfonamides and Amides Derivatives: Design,Synthesis, and Antitumor Activity In Vitro

Coumarins possesses immeasurable antitumor potential with minimum side effects depending on the substitutions on the basic nucleus, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, a series of coumarin sulfonamides and amides derivatives were designed and synthetized. The majority of these derivatives showed good cytotoxic activity against MDA-MB-231 and KB cell lines, among which compound 9c was the most potent against MDA-MB-231 cells, with IC₅₀ value of 9.33 μM, comparable to 5-fluorouracil. Further investigation revealed that compound 9c had versatile properties against tumors, including inhibition of cell migration and invasion as well as inducing apoptosis. Reactive oxygen species (ROS) assay and western blotting analysis suggested that compound 9c promoted cancer cell apoptosis by increasing ROS levels and upregulating the expression of caspase-3 in MDA-MB-231 cells. These results indicated that compound 9c could be promising lead compound for further antitumor drug research.     

A mononuclear copper(II) complex containing benzimidazole and pyridyl ligands: Synthesis,characterization, and antiproliferative activity against human cancer cells

Metal complexes are recently being hybridized with different moieties to discover new drugs due to their advantageous attributes. Among the metals, copper is a good one to synthesize a metal complex due to its being endogenous, redox and DNA cleavage potential, reported anti-cancer efficacies and selective permeability for cancer cells. In this study, first we synthesized a new copper (II) complex and determined its toxic doses on NIH/3T3 normal fibroblast cells, SPC212 mesothelioma and DU145 prostate cancer cells. Then, we ascertained anti-proliferative, apoptotic, morphological, oxidative and endoplasmic reticulum (ER) stress inducing effects of these newly synthesized compounds on DU145 prostate cancer cells. A novel Copper(II)/1-(4-(trifluoromethyl)benzyl)-1H-benzimidazole/2,2′-bipyridyl complex was synthesized and mainly characterized by single crystal X-ray diffraction analysis. Anti-proliferative effect of copper(II) complex was gauged by MTT. Oxidative and ER stress were evaluated by ELISA and Western blot. The morphological effect was examined by microscope analysis. Besides, immunocytochemistry of Bax, a pro-apoptotic protein and PCNA, a proliferation marker protein was performed. As a result, the inhibitory effect of newly synthesized substance was superior to the chemicals from which it was synthesized. Its IC₅₀s against DU145 were 37.0, 21.1 and 10.0 µM for 24, 48 and 72 h-treatments, respectively. Oxidative and ER stress increased after treatment. In microscopy, we observed apoptotic hallmarks like nuclear condensation, cellular shrinkage and membrane blebbings. In immunochemistry, increased Bax and decreased PCNA were apparent. Copper(II) complex with its relatively low IC₅₀ can also be tested on other cancer and normal cell lines.     

Synthesis and In Vitro Anticancer Activity of Novel 1,3,4‐Oxadiazole‐Linked 1,2,3‐Triazole/Isoxazole Hybrids

A series of new 1,3,4‐oxadiazole‐linked 1,2,3‐triazole/isoxazole derivatives were designed and synthesized. All the synthesized compounds were screened for in vitro anticancer activity against four human cancer cells: HeLa (cervical), MDA‐MB‐231 (breast), DU‐145 (prostate), and HEPG2 (liver). Among 17 compounds tested, 7a , 7c , and 7d showed potent activity toward four cell lines.     

Suppressed Migration and Enhanced Cisplatin Chemosensitivity in Human Cancer Cell Lines by Tuning the Molecular Mobility of Supramolecular Biomaterials

Cancer cells recognize physical cues transmitted from the surrounding microenvironment, and accordingly alter the migration and chemosensitivity. Cell adhesive biomaterials with tunable physical properties can contribute to the understanding of cancer cell responses, and development of new cancer therapies. Previously, it was reported that polyrotaxane-based surfaces with molecular mobility effectively modulate cellular functions via the yes-associated protein (YAP)-related signaling pathway. In the present study, the impact of molecular mobility of polyrotaxane surfaces on the migration and chemosensitivity of lung (A549), pancreatic (BxPC-3), and breast cancer (MDA-MB-231) cell lines is investigated, and it is found that the cellular spreading of adherent A549 and BxPC-3 cells and nuclear YAP translocation are promoted on low-mobility surfaces, suggesting that cancer cells alter their subcellular YAP localization in response to molecular mobility. Furthermore, low-mobility surfaces suppress cellular migration more than high-mobility surfaces. Additionally, low-mobility surfaces promote the cisplatin chemosensitivity of each cancer cell line to a greater extent than high-mobility surfaces. These results suggest that the molecular mobility of polyrotaxane surfaces suppresses cellular migration and enhances chemosensitivity via the subcellular translocation of YAP in cancer cells. Biointerfaces based on polyrotaxanes can thus be a new platform for elucidating cancer cell migration and chemoresistance mechanisms.