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Spectrochimica Acta. Part A, Molecular... Jun 2023This study represents detailed vibrational analysis of naphthalene bisbenzimidazole (NBBI), perylene bisbenzimidazole (PBBI), and naphthalene imidazole (NI) by...
Heterojunction solar cell based on donor-acceptor pi-conjugated naphthalene bisbenzimidazole, perylene bisbenzimidazole, and naphthalene imidazole: A spectroscopic, microscopic and DFT assessment.
This study represents detailed vibrational analysis of naphthalene bisbenzimidazole (NBBI), perylene bisbenzimidazole (PBBI), and naphthalene imidazole (NI) by vibrational spectroscopic (Fourier Transform Infrared (FT-IR) and Raman), Atomic Force Microscopic (AFM) and quantum chemical studies for the first time. These sorts of compounds provide an opportunity to build potential n-type organic thin film phototransistors which can be used as organic semiconductors. Optimized molecular structures and vibrational wavenumbers of these molecules in their ground states have been calculated by Density Functional Theory (DFT) using B3LYP functional with 6-311++G(d,p) basis set. Finally, theoretical UV-Visible spectrum was predicted and Light Harvesting Efficiencies (LHE) were evaluated. AFM analysis revealed that PBBI has the highest surface roughness thus exhibits an increase in high Jsc value and high conversion efficiency.
PubMed: 36868025
DOI: 10.1016/j.saa.2023.122516 -
Phytomedicine : International Journal... Sep 2023Triple-negative breast cancer (TNBC) is a heterogeneous carcinoma characterized by the most aggressive phenotype among all breast cancer subtypes. However, therapeutic...
Calycosin inhibits triple-negative breast cancer progression through down-regulation of the novel estrogen receptor-α splice variant ER-α30-mediated PI3K/AKT signaling pathway.
BACKGROUND
Triple-negative breast cancer (TNBC) is a heterogeneous carcinoma characterized by the most aggressive phenotype among all breast cancer subtypes. However, therapeutic options for TNBC patients have limited clinical efficacy due to lack of specific target and efficient targeted therapeutics.
AIM
To investigate the biological characteristics of a novel estrogen receptor (ER)-α splice variant ER-α30 in breast cancer cells, and its possible role in the anticancer effects of calycosin, a typical phytoestrogen derived from the herbal plant Astragalus membranaceus, against TNBC. This may also provide a better understanding of the inhibitory activity of calycosin on TNBC progression.
METHODS
Breast cancer tissues and para-cancer tissues were collected and analyzed for the expression levels of ER-α30 using immunohistochemistry (IHC), and its expression in two TNBC cell lines (MDA-MB-231 and BT-549) was detected by western blot and qRT-PCR assays. Then the alteration of cell viability, apoptosis, migration, invasion and epithelial-mesenchymal transition (EMT) in response to overexpression or knockdown of ER-α30 was separately determined by CCK-8, Hoechst 33258, wound healing, transwell and western blot assays in two TNBC cell lines. Next, the anticancer effects of calycosin on MDA-MB-231 cells were evaluated through CCK-8, colony formation, flow cytometry, Hoechst 33258 and western blot assays, along with the role of ER-α30 in these effects and the possible downstream targets of ER-α30. In addition, the in vivo experiments were carried out using MDA-MB-231 xenograft model intraperitoneally treated with calycosin. The volume and weight of xenograft tumor were measured to evaluate the in vivo anticancer activities of calycosin, while the corresponding changes of ER-α30 expression in tumor tissues were detected by IHC.
RESULTS
It was demonstrated that the novel ER-α splice variant ER-α30 was primarily distributed in the nucleus of TNBC cells. Compared with normal breast tissues, ER-α30 expression was found in significantly higher levels in breast cancer tissues of ER- and progesterone receptor (PR)-negative subtype, so did in TNBC cell lines (MDA-MB-231 and BT-549) when compared to normal breast cell line MCF10A. Moreover, ER-α30 overexpression strikingly enhanced cell viability, migration, invasion and EMT progression and reduced apoptosis in TNBC cells, whereas shRNA-mediated knockdown of ER-α30 revealed the opposite results. Notably, calycosin suppressed the expression of ER-α30 in a dose-dependent manner, accompanied with the inhibition of TNBC growth and metastasis. A similar finding was observed for the xenografts generated from MDA-MB-231 cells. The treatment with calycosin suppressed the tumor growth and decreased ER-α30 expression in tumor tissues. Furthermore, this inhibition by calycosin was more pronounced in ER-α30 knockdown cells. Meanwhile, we found a positive relationship between ER-α30 and the activity of PI3K and AKT, which could also be inactivated by calycosin treatment.
CONCLUSION
For the first time, it is demonstrated that the novel estrogen receptor-α splice variant ER-α30 could function as pro-tumorigenic factor in the context of TNBC by participating in cell proliferation, apoptosis, invasion and metastasis, thus it may serve as a potential therapeutic target for TNBC therapy. Calycosin could reduce the activation of ER-α30-mediated PI3K/AKT pathway, thereby inhibited TNBC development and progression, suggesting that calycosin may be a potential therapeutic option for TNBC.
Topics: Humans; Triple Negative Breast Neoplasms; Proto-Oncogene Proteins c-akt; Receptors, Estrogen; Phosphatidylinositol 3-Kinases; Down-Regulation; Bisbenzimidazole; Sincalide; Cell Line, Tumor; Signal Transduction; Cell Proliferation; Cell Movement
PubMed: 37393829
DOI: 10.1016/j.phymed.2023.154924 -
Mikrochimica Acta Dec 2023Co-based coordination polymers (CoCP) based on 4,4'-bis(1H-benzo[d]imidazol-1-yl)-1,1'-biphenyl (BMB) ligand have been synthesized for the first time by the solvothermal...
Co-based coordination polymers (CoCP) based on 4,4'-bis(1H-benzo[d]imidazol-1-yl)-1,1'-biphenyl (BMB) ligand have been synthesized for the first time by the solvothermal method. The CoCP was carbonized at 700 °C under a nitrogen atmosphere to obtain carbide coordination polymer (C-CoCP) with a unique two-dimensional layered network structure. C-CoCP@GO was obtained by binding with GO and C-CoCP, its morphology and structure were investigated by XRD, SEM, EDS, FTIR, and TGA, which confirmed its two-dimensional stacked layered structure with high catalytic activity and large specific surface area. A highly sensitive electrochemical sensor was constructed for the simultaneous detection of hydroquinone and catechol based on the prepared carbon-based composite. Under optimized conditions, the working potentials (vs. Ag/AgCl) of HQ and CC are at 0.097 V and 0.213 V, respectively. The sensor exhibited an extremely wide linear range of 3-600 μM and 3-1750 μM for hydroquinone (HQ) and catechol (CC), respectively, with limits of detection (LOD) of 0.46 μM and 0.27 μM. The electrode material demonstrated stability over 14 days without significant attenuation of the response signal. Impressively, the sensor shows high stability, reproducibility, and selectivity due to the stable carbon skeleton structure of the C-CoCP material. In addition, it can be applied to the detection of hydroquinone in real samples with high interference immunity and high recovery. Hence, the C-CoCP@GO composite proved to be a great prospect and highly sensitive sensing platform for the detection of phenolic isomers.
PubMed: 38091124
DOI: 10.1007/s00604-023-06099-x -
ACS Omega Nov 2023Rhenium(I)tricarbonyl core-based heteroleptic "figure-eight"- and Z-shaped metallocycles (-) of the general formula -[{(CO)Re(μ-L)Re(CO)}(dppz)] were self-assembled...
Rhenium-Pyrazolyl-Based Figure-Eight- and Z-Shaped Metallocycles: Self-Assembly, Solid-State Structures, Dynamic Properties in Solution, and Competitive Ligand-Induced Supramolecular Transformations into Rhenium-Pyridyl/-Benzimidazolyl/-Phosphine-Based Metallocycles/Acyclic Complexes.
Rhenium(I)tricarbonyl core-based heteroleptic "figure-eight"- and Z-shaped metallocycles (-) of the general formula -[{(CO)Re(μ-L)Re(CO)}(dppz)] were self-assembled from Re(CO), H-L (H-L = 5,8-dihydroxy-1,4-naphthaquinone (H-dhnq) for ; 1,4-dihydroxy-9,10-anthraquinone (H-dhaq) for ; 6,11-dihydroxy-5,12-naphthacenedione (H-dhnd) for ; 2,2'-bisbenzimidazole (H-bbim) for ), and bis(4-((pyrazolyl)methyl)phenylmethane) (dppz) via one-pot coordination-driven synthetic approach. The molecular structures of and were unambiguously confirmed by single-crystal X-ray diffraction (SC-XRD) methods. The metallocycles in the DMSO solution exist as an acyclic dinuclear-DMSO adduct of the general formula -[{(CO)Re(μ-L)Re(CO)}(DMSO)] (, L = dhnq; , L = dhaq; , L = dhnd; , L = bbim) and dppz, which are in dynamic equilibrium. The dynamic behavior of the rhenium-pyrazolyl bond in the solution state was effectively utilized to transform metallocycles - into pyridyl/benzimidazolyl/phosphine donor-based heteroleptic metallocycles and acyclic dinuclear complexes (-). These include tetranuclear rectangles -[{(CO)Re(μ-L)Re(CO)}(4,4'-bpy)] ( and , L = dhaq for and bbim for ), dinuclear metallocycles -[{(CO)Re(μ-L)Re(CO)}(dpbim)] (- and ; L = dhnq for , dhaq for , dhnd for , and bbim for ), and dinuclear acyclic complexes -[{(CO)Re(μ-L)Re(CO)}(PTA)] (- and ; L = dhnq for , dhaq for , dhnd for , and bbim for ). These transformations were achieved through component-induced supramolecular reactions while treating with competitive ligands 4,4'-bipyridine (4,4'-bpy), bis(4-((1-benzoimidazole-1-yl)methyl)phenyl)methane (dpbim), and 1,3,5-triaza-7-phosphaadamantane (PTA). The reaction mixture in the solution was analyzed using NMR and electrospray ionization mass spectrometry (ESI-MS) analysis. Additionally, crystal structures of , , and , which were obtained in the mixture of the solutions, were determined, providing unequivocal evidence for the occurrence of supramolecular transformation within the system. The results reveal that the size of the chelating ligand and the pyrazolyl donor angle of the ditopic ligand play crucial roles in determining the resulting solid-state metallacyclic architecture in these synthetic combinations. The dynamic behavior of the rhenium-pyrazolyl bond in the metallocycles can be utilized to transform into other metallocycles and acyclic complexes using suitable competing ligands via ligand-induced supramolecular transformations.
PubMed: 37969972
DOI: 10.1021/acsomega.3c06371 -
Inorganic Chemistry May 2024Ancillary ligand scaffolds that sufficiently stabilize a metal ion to allow its coordination to an open-shell ligand are scarce, yet their development is essential for...
Ancillary ligand scaffolds that sufficiently stabilize a metal ion to allow its coordination to an open-shell ligand are scarce, yet their development is essential for next-generation spin-based materials with topical applications in quantum information science. To this end, a synthetic challenge must be met: devising molecules that enable the binding of a redox-active ligand through facile displacement and clean removal of a weakly coordinating anion. Here, we probe the accessibility of unprecedented radical-containing rare-earth guanidinate complexes by combining our recently discovered yttrium tetraphenylborate complex [{(MeSi)NC(NPr)}Y][(μ-η-Ph)(BPh)] with the redox-active ligands 2,2'-bipyridine (bpy) and 2,2'-bis(benzimidazole) (Bbim), respectively, under reductive conditions. Our endeavor resulted in the first evidence of guanidinate complexes that contain radicals, namely, a mononuclear bipyridyl radical complex, {(MeSi)NC(NPr)}Y(bpy) (), and a dinuclear bis(benzimidazolyl) radical-bridged complex, [K(crypt-222)][{(MeSi)NC(NPr)}Y](μ-Bbim) (). The latter was achieved by an in situ reduction of [{(MeSi)NC(NPr)}Y](μ-Bbim) (), which was isolated from a salt metathesis reaction. and were characterized by X-ray crystallography and IR and UV-vis spectroscopy. Variable-temperature electron paramagnetic resonance spectroscopy was applied to gain insight into the distribution of unpaired spin density on and . Density functional theory calculations were conducted on and to elucidate further their electronic structures. The redox activity of and was also probed by electrochemical methods.
PubMed: 38569134
DOI: 10.1021/acs.inorgchem.4c00006 -
Chemistry (Weinheim An Der Bergstrasse,... Nov 2023A new series of highly soluble perylene anti-bis(4,5-dialkoxybenzimidazole)s bearing branched flexible chains stabilizing room temperature columnar hexagonal phase and...
A new series of highly soluble perylene anti-bis(4,5-dialkoxybenzimidazole)s bearing branched flexible chains stabilizing room temperature columnar hexagonal phase and with balanced ambipolar charge carrier mobility is reported for the first time. Only the anti isomer was successfully separated and characterized. These compounds have a high extinction coefficient, small optical band gap and wide absorption range, thus making them a promising class of ambipolar organic semiconductors capable of self-organizing.
PubMed: 37529862
DOI: 10.1002/chem.202302187 -
Molecules (Basel, Switzerland) Jun 2023Heteroaromatic polyimides (PIs) containing benzimidazole have attracted tremendous attention due to their positive impact on the properties of PIs. Some research on PIs...
Heteroaromatic polyimides (PIs) containing benzimidazole have attracted tremendous attention due to their positive impact on the properties of PIs. Some research on PIs containing 4,4'-[5,5'-bi-1-benzimidazole]-2,2'-diylbis-benzenamine () has been reported. However, reports are lacking on homo-polyimides (homo-PIs) containing 3,3'-[5,5'-bi-1-benzimidazole]-2,2'-diylbis-benzenamine (), which is one of the isomers of . In this paper, the influence of amino groups' positions on the performance of homo-PIs was investigated. It was found that the net charge of the amine N group in was lower than that of , resulting in higher reactivity of . Consequently, PIs containing displayed better mechanical performance. Molecular simulation confirmed that and its corresponding PI chain exhibited distorted conformation, leading to the PI films containing having a lighter color. In addition, the structure was calculated to have higher rotational energy compared to , resulting in a higher glass transition temperature () in PIs prepared from . On the other hand, PIs containing exhibited a higher level of molecular linearity, leading to a lower coefficient of thermal expansion (CTE) compared to PIs prepared from . Furthermore, all PIs showed higher thermal stability with a 5% weight loss temperature above 530 °C and higher than 400 °C.
Topics: Humans; Benzimidazoles; Aniline Compounds; Diamines; Fever
PubMed: 37446551
DOI: 10.3390/molecules28134889 -
Microbiology Spectrum Apr 2024We previously identified the bisbenzimide Hoechst 33342 (H42) as a potent multi-stage inhibitor of the prototypic poxvirus, the vaccinia virus (VACV), and several...
We previously identified the bisbenzimide Hoechst 33342 (H42) as a potent multi-stage inhibitor of the prototypic poxvirus, the vaccinia virus (VACV), and several parapoxviruses. A recent report showed that novel bisbenzimide compounds similar in structure to H42 could prevent human cytomegalovirus replication. Here, we assessed whether these compounds could also serve as poxvirus inhibitors. Using virological assays, we show that these bisbenzimide compounds inhibit VACV spread, plaque formation, and the production of infectious progeny VACV with relatively low cell toxicity. Further analysis of the VACV lifecycle indicated that the effective bisbenzimide compounds had little impact on VACV early gene expression but inhibited VACV late gene expression and truncated the formation of VACV replication sites. Additionally, we found that bisbenzimide compounds, including H42, can inhibit both monkeypox and a VACV mutant resistant to the widely used anti-poxvirus drug TPOXX (Tecovirimat). Therefore, the tested bisbenzimide compounds were inhibitors of both prototypic and pandemic potential poxviruses and could be developed for use in situations where anti-poxvirus drug resistance may occur. Additionally, these data suggest that bisbenzimide compounds may serve as broad-activity antiviral compounds, targeting diverse DNA viruses such as poxviruses and betaherpesviruses.IMPORTANCEThe 2022 mpox (monkeypox) outbreak served as a stark reminder that due to the cessation of smallpox vaccination over 40 years ago, most of the human population remains susceptible to poxvirus infection. With only two antivirals approved for the treatment of smallpox infection in humans, the need for additional anti-poxvirus compounds is evident. Having shown that the bisbenzimide H33342 is a potent inhibitor of poxvirus gene expression and DNA replication, here we extend these findings to include a set of novel bisbenzimide compounds that show anti-viral activity against mpox and a drug-resistant prototype poxvirus mutant. These results suggest that further development of bisbenzimides for the treatment of pandemic potential poxviruses is warranted.
Topics: Humans; Poxviridae; Bisbenzimidazole; Smallpox; Pandemics; Vaccinia virus
PubMed: 38376353
DOI: 10.1128/spectrum.04072-23 -
Journal of Biomolecular Structure &... Jun 2024Interaction of the minor groove binder, Hoechst 33258, with the Dickerson-Drew DNA dodecamer sequence has been investigated using docking, MM/QM, MM/GBSA and molecular...
Interaction of the minor groove binder, Hoechst 33258, with the Dickerson-Drew DNA dodecamer sequence has been investigated using docking, MM/QM, MM/GBSA and molecular dynamics computations to study the modes of binding and the interactions responsible for the binding. Besides the original Hoechst 33258 ligand (), a total of 12 ionization and stereochemical states for the ligand are obtained at the physiological pH and have been docked into B-DNA. These states have one or the other or both benzimidazole rings in protonated states, apart from the piperazine nitrogen, which has a quaternary nitrogen in all the states. Most of these states are found to exhibit good docking scores and free energy of binding with B-DNA. The best docked state has been taken further for molecular dynamics simulations and compared with the original . This state is protonated at both benzimidazole rings besides the piperazine ring and hence has very highly negative coulombic interaction energy. In both cases, there are strong coulombic interactions, but these are offset by the almost equally unfavorable solvation energies. Thus, the nonpolar forces, particularly van der Waals contacts, dominate the interaction, and the polar interactions highlight subtle changes in the binding energies, leading to more highly protonated states having more negative binding energies.Communicated by Ramaswamy H. Sarma.
Topics: Molecular Dynamics Simulation; DNA, B-Form; Bisbenzimidazole; Molecular Docking Simulation; Ligands; Thermodynamics; Hydrogen Bonding; Nucleic Acid Conformation; Binding Sites; Computer Simulation
PubMed: 37301606
DOI: 10.1080/07391102.2023.2220807 -
ACS Applied Materials & Interfaces Mar 2024Natural copper oxygenases provide fundamental principles for catalytic oxidation with kinetically inert molecular oxygen, but it remains a marked challenge to mimic both...
Natural copper oxygenases provide fundamental principles for catalytic oxidation with kinetically inert molecular oxygen, but it remains a marked challenge to mimic both their structure and function in an entity. Inspired by the Cu enzymatic sites, herein we report two new photoactive binuclear copper-iodine- and bisbenzimidazole-comodified coordination polymers to reproduce the natural oxo-functionalization repertoire in a unique photocatalytic pathway. Under light irradiation, the Cu-halide coordination polymers effectively reduce NHP esters and complete oxygen reduction activation via photoinduced electron transfer for the aerobic oxidative coupling of hydroquinone with terminal alkynes, affording hydroxyl-functionalized ketones with high efficiency and selectivity. This supramolecular approach to developing bioinspired artificial oxygenases that merge transition metal- and photocatalysis supplies a new way to fabricate distinctive photocatalysts with desirable catalytic performances and controllable precise active sites.
PubMed: 38451748
DOI: 10.1021/acsami.3c17175