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•A range of new scaffolds based on pyridine based chalcones were synthesized and characterized using analytical and spectroscopic methods.•All synthesized compounds were tested for ...anticancer and antioxidant activities.•Compounds3a, 3d, 3e, 3f, and 3j showed promising activities against Human Breast Cancer Cell Line MDA-MB-231.•The results were compared to that of the in silico molecular docking and ADME studies.
A novel class of chalcones were synthesized via the Claisen-Schmidt condensation of 6-chloropyridine-3-carbaldhyde with various ortho, meta, and para substituted acetophenones in the presence of a base and a polar protic solvent. The newly synthesized compounds were characterized by using various spectral techniques 1H NMR, 13C NMR, FT-IR, and mass spectroscopy methods. All newly synthesized compounds were evaluated in vitro for anticancer activity against the Human Breast Cancer Cell Line MDA-MB-231, and antioxidant activity was quantified using the DPPH free radical scavenging technique. The anticancer screening findings revealed that the synthesized compounds 3a, 3d, 3e, 3f, and 3j had GI50 of < 10 μg/mL. The compounds 3a and 3j have showed excellent antioxidant activity. Molecular docking simulations have been done against inhibitor of the human estrogen receptor alpha enzyme (PDB ID: 2iog) found that compounds 3a, 3d, 3e, 3f, and 3j have a high binding energy (−7.8 to −8.8 Kcal/mol). The in silico ADME properties of the synthesized compounds (3a-3j) demonstrated that they are very good oral bioavailability medications.
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•Synthesis of ZrO2 nanoparticles by facile, cost effective sol-gel method.•ZrO2 nanoparticles were characterized by different techniques.•Toxicity assessment of ZrO2 nanoparticles ...against MDA-MB-231 cell line.•Agar well diffusion assay of ZrO2 nanoparticles against bacterial strains.•DPPH and nitric oxide scavenging assay of ZrO2 nanoparticles was measured.
Health care costs of antibiotic resistance to the community have been astounding over the last decade and require urgent attention. This calls for new alternatives, such as metal oxide nanomaterials, to be considered at a more extended level. Metal oxide nanomaterials have been exerting a pull-on deal with its complete applications in biological and pharmaceutical fields of nanobiotechnology. The present study addresses the synthesis of nanoparticles of the zirconium oxide (ZrO2) by a process that can be quickly, economically and industrially used to combat deadly pathogens. The biological activity of synthesized zirconium oxide nanoparticles against bacterial strains has been studied by using agar well diffusion method. Besides, DPPH (1,1-diphenyl-2-picryl hydrazyl) and a nitrous oxide-scavenging study, we have also studied the antioxidant ability of ZrO2 nanoparticles along with the anticancer activity. Importantly, our research demonstrated the antimicrobial activity of ZrO2 nanoparticles at different concentrations comparable to standard antibiotics against gram-positive bacteria (Staphylococcus aureus) and gram-negative bacteria (Klebsiella pneumonia), respectively. We believe that the synthesized ZrO2 nanoparticles demonstrated inhibitive activity against K. pneumoniae by the attraction of negatively charged K. pneumoniae cell wall against positively charged zirconium ions. Our findings suggest that synthesized multifunctional ZrO2 nanoparticles may be a successful candidate in health care systems.
Perfluoroalkyl substances (PFASs) are a category of high-concerned emerging contaminants which are suspected to correlate with various human adverse health outcomes including tumors. It is also a ...question whether short-chain PFASs are qualified alternatives under the regulation of long-chain PFASs. In this study, a three-dimensional (3D) culture system based on Gelatin methacrylate (GelMA) hydrogel matrix was used to investigate the impacts of 120-h perfluorooctanoic acid (PFOA) and perfluorobutanoic acid (PFBA) exposure of MDA-MB-231 cells. The results showed that PFOA exposure promoted the proliferation, migration, and invasion of MDA-MB-231 cells in an environmentally relevant concentration range (0.1 to 10 μM), exhibiting a clear malignant-promoting risk. In contrast, PFBA only showed a trend to induce non-invasive cell migration. Hippo/YAP signaling pathway was identified as the contributor to the differences between the two PFASs. PFOA but PFBA reduced YAP phosphorylation and increased the nuclear content of YAP, which further facilitated abundant key factors of epithelial-mesenchymal transition (EMT) process. Our results provided a new idea for the carcinogenicity of PFOA using a 3D-based paradigm. Although the effects by PFBA were much milder than PFOA in the current test duration, the cell model suitable for longer exposure is still necessary to better assess the safety of alternative short-chain PFASs.
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•A 3D cell culture system was constructed by GelMA hydrogel based on ECM-like properties.•PFOA exposure promotesmigration, and invasion of TNBC cells, and PFBA exhibits a tendency to induce only non-invasive migration.•Hippo pathway and its effector protein YAP were identified as factors contributing to the differences between the two PFASs.•YAP entry into the nucleus leads to EMT process in TNBC cells under the influence of PFOA.
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•Synthesis and characterization of fluorescence receptors N1, N2-bis(2-piperazine-1-yl) ethyl) oxalamide OX(PIP)2 and Di-(benzoyloxalohydrazide) OX(BH)2 for detecting Sn2+ and Fe3+ ...ions.•Absorbance and fluorescence spectral activity of the OX(PIP)2 & OX(BH)2 receptors for Sn2+/Fe3+ ions.•Gelation ability of receptor with various solvent.•CT-DNA binding studies with fluorescence receptors with their Sn2+/Fe3+ ions.•Investigate the antibacterial activity, anticancer activity and cell imaging properties.
The development of colorimetric and fluorescence receptors N1, N2-bis(2-piperazine-1-yl)ethyl)oxalamide OX(PIP)2 and Di-(benzoyloxalohydrazide) OX(BH)2 for the accurate and easily identified Sn2+ & Fe3+ ions respectively in DMSO/HEPES buffer (1:9, v/v, 20 μM, pH 7.3) was a success. The process of sensing entails the complexation of OX(PIP)2 receptors with Sn2+ addition, which sets off the fluorescence 'Turn-On' mode and OX(BH)2 displays ‘Turn-Off’ mode after the inclusion of Fe3+ ions. An improved linear correlation between fluorescence intensity and Sn2+/Fe3+ concentration was attained in the range of 0–20 μM, with a detection limit (LOD) of 0.6 μM & 0.013 μM respectively. The average fluorescence lifespan measurements of OX(PIP)2 and OX(BH)2 were determined to be 2.77 and 2.22 ns, and the average life time of 4.49 ns for OX(PIP)2 + Sn2+ and 2.18 ns for OX(BH)2 + Fe3+ were observed. The binding mechanisms of OX(PIP)2 + Sn2+ and OX(BH)2 + Fe3+ were confirmed by Fourier transform infrared analysis, NMR spectral titrations, and mass (ESI) spectral analysis. The chemosensing of OX(PIP)2 and OX(BH)2 has also been examined in bioimaging experiments as useful fluorescent markers for finding the source of Sn2+/Fe3+ in living cells. Significantly, receptors OX(PIP)2 and OX(BH)2 could distinguish Sn2+/Fe3+ ions in live cells and Sn2+/Fe3+ in human cancer cells.
The successful targeting of tumors can be achieved by conjugating targeting moieties to nanoparticles. These modifications allow nannocarriers to achieve greater targeting specificity through binding ...to specific receptors overexpressed on the surface of the tumor cells. In this study, pegylated liposomes encapsulating the model drug/dye calcein and conjugated to hyaluronic acid (HA) molecules were successfully synthesized, and their ability to target HA receptors overexpressed on a breast cancer cell line was investigated
. Low-frequency ultrasound (LFUS), applied at three different power densities (6.2, 9, and 10 mW/cm²) were used to trigger the release of the entrapped calcein. Both the control and HAconjugated liposomes showed similar release profiles. HA conjugation to the liposomes resulted in a significant increase in calcein uptake by the breast cancer cell line MDA-MB-231 known for its CD44 (HA receptor) overexpression, while such an effect was not recorded with NIH-3T3, an embryonic mouse fibroblast, with low levels of CD44 expression. The application of low LFUS showed a significant enhancement of calcein uptake by MDA-MB-231 cells from our liposome compared to calcein uptake without cell exposure to ultrasound. These findings suggest that combining HA-conjugated liposomes with ultrasound is a promising drug delivery platform in breast cancer treatment.
The N1,N2‐diphenyloxalohydrazide OX(HA)2 chemosensor was synthesized and used as a colorimetric and fluorescent receptor to detect Cu2+ and Fe3+ ions in the presence of other metal ions. A range of ...physicochemical approaches were utilized to characterize the symmetrical oxalohydrazide‐based receptor, including FT‐IR, 1H and 13C NMR, TGA, and mass spectrometry. According to single crystal X‐ray diffraction investigation, OX(HA)2 crystallizes in monoclinic with space group C2/c. UV‐Vis and fluorescence spectroscopy were used to thoroughly explore OX(HA)2’s sensing capabilities towards diverse cations. Using measurements of fluorescence intensity, the binding constant for OX(HA)2 with Cu2+/Fe3+ ions was calculated to be 2.78×103 M−1 and 1.12×103 M−1 with the lower detection limit of 0.43 μM and 0.2 μM respectively. With a 1 : 1 binding mechanism validated by Job's plot, mass spectral analysis, FT‐IR spectra, and density functional theory, the dual‐sensing receptor exhibits remarkable selectivity and sensitivity towards Cu2+ and Fe3+ ions. The average fluorescence lifetimes of OX(HA)2, OX(HA)2+Cu2+, and OX(HA)2+Fe3+ were calculated to be 2.19 ns, 1.73 ns, and 1.26 ns, respectively. This fluorescence lifetime measurement results strongly support the complexation of Cu2+ and Fe3+. When Cu2+ and Fe3+ ions bind with OX(HA)2, they induce the ‘Turn‐Off’ signal. Then, fluorescence imaging of the OX(HA)2 receptor in MDA‐MB‐231 demonstrated that the receptor holds a lot of promise for usage in bioimaging and their IC50 value for cytotoxicity is 96.96 μg. Furthermore, fluorescence microscopy experiments demonstrate that OX(HA)2 can be utilized as a fluorescent probe for detecting Cu2+ and Fe3+ ions in living cells, making it potentially helpful as an anticancer medication.
New N1,N2‐diphenyloxalohydrazide‐based receptor OX(HA)2 was synthesized and evaluated. When compared to other metal ions, the receptor has a highly specific selectivity for Cu2+/Fe3+ with a fluorescence “Turn‐Off” effect and detection limits of 1.25×103 M−1 and 1.28×103 M−1, respectively. Moreover, the fluorescence imaging in MDA‐MB‐231 cells suggested that chemosensors had great potential in the application of bioimaging. The cell viability of receptor OX(HA)2 decreases with increasing concentration of the receptor, and the IC50 values of the receptor was found to be 96.96 μg.
Drug resistance in breast cancer remains a major obstacle of clinical therapy. We found that suppression of ELK3 in the triple negative breast cancer cell line MDA-MB-231 impaired autophagy and led ...to a hypersensitive response to doxorubicin treatment. In ELK3-knockdown MDA-MB-231 cells (ELK3 KD), autophagy was not activated under starvation conditions, which is a major stimulus of autophagy activation. We revealed that activation of the PI3K/Akt pathway was the main cause of impaired autophagy in ELK3 KD. Our results suggest that targeting ELK3 may be a potential approach to overcome doxorubicin resistance in breast cancer therapeutics.
•Autophagy is impaired by suppression of ELK3 in the triple negative breast cancer cell line, MDA-MB-231.•ELK3 inhibits autophagy through activation of the PI3K-Akt signaling pathway.•ELK3 suppressed MDA-MB-231 cells are doxorubicin-sensitive due to the impaired autophagy.
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