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Acta Naturae 2024Its broad spectrum of biological activity makes benzimidazole a fundamental pharmacophore in pharmaceutics. The paper describes newly synthesized AT-specific fluorescent...
Its broad spectrum of biological activity makes benzimidazole a fundamental pharmacophore in pharmaceutics. The paper describes newly synthesized AT-specific fluorescent bis-benzimidazole molecules DB2Py(n) that contain a pyrrolcarboxamide fragment of the antibiotic drug netropsin. Physico-chemical methods using absorption, fluorescence, and circular dichroism spectra have shown the ability of bis-benzimidazole- pyrroles to form complexes with DNA. The new DB2Py(n) series have turned out to be more toxic to human tumor lines and less vulnerable to non-tumor cell lines. Bis-benzimidazole-pyrroles penetrated the cell nucleus, affected the cell-cycle synthesis (S) phase, and inhibited eukaryotic topoisomerase I in a cellfree model at low concentrations. A real-time tumor cell proliferation test confirmed the molecule's enhanced toxic properties upon dimerization. Preliminary cytotoxicity data for the bis-benzimidazole-pyrroles tested in a cell model with a MDR phenotype showed that monomeric compounds can overcome MDR, while dimerization weakens this ability to its intermediate values as compared to doxorubicin. In this respect, the newly synthesized cytotoxic structures seem promising for further, in-depth study of their properties and action mechanism in relation to human tumor cells, as well as for designing new AT-specific ligands.
PubMed: 38698958
DOI: 10.32607/actanaturae.27327 -
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 -
Lasers in Medical Science Feb 2024To investigate the effects of photodynamic therapy (PDT) mediated by hematoporphyrin derivatives (HPD) on the proliferation of small cell lung cancer H446 cells and...
To investigate the effects of photodynamic therapy (PDT) mediated by hematoporphyrin derivatives (HPD) on the proliferation of small cell lung cancer H446 cells and bronchial epithelial BEAS-2B cells. H446 cells and BEAS-2B cells were cultured in vitro with different concentrations of HPD(0, 5, 10, 12, 15, 20 μg/mL) for 4 h, and then irradiated with 630 nm laser with different energy densities (0, 25, 50, 75, 100 mW/cm2). Cell viability of H446 cells and BEAS-2B cells were detected by CCK8 assay. The cell apoptosis was observed with Annexin V-FTTC/PI double staining and Hoechst 33258. The RT-PCR examination was applied to detect the transcriptional changes of the mRNA of Bax、Bcl-2, and Caspase-9. The results of CCK8 showed that when the HPD was 15 μg/mL and the laser power density reached 50 mW/cm2, the cell viability was significantly decreased compared with the black control group. Hoechst 33258 staining showed that with the increase of HPD concentration, the cell density was reduced, and apoptotic cells increased. Flow cytometry assay revealed that the apoptotic rates of the HPD-PDT group of H446 cells and BEAS-2B cells were significantly different from those of the blank control group. The RT-PCR examination showed that the expression levels of Bax and Caspase-9 mRNA in the HPD-PDT group were up-regulated, while the expression levels of Bcl-2 mRNA were down-regulated significantly. HPD-PDT can inhibit H446 cells and BEAS-2B cells growth. The mechanism may be related to up-regulating the expression levels of Bax and Caspase-9 mRNA and down-regulating the expression levels of Bcl-2 mRNA.
Topics: Humans; Hematoporphyrin Derivative; Small Cell Lung Carcinoma; Caspase 9; Lung Neoplasms; bcl-2-Associated X Protein; Bisbenzimidazole; Photochemotherapy; Epithelial Cells; Apoptosis; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger
PubMed: 38368311
DOI: 10.1007/s10103-024-04013-2 -
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 -
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 -
International Journal of Molecular... May 2023The bis-benzimidazole derivative (BBM) molecule, consisting of two 2-(2'-hydroxyphenyl) benzimidazole (HBI) halves, has been synthesized and successfully utilized as a...
The bis-benzimidazole derivative (BBM) molecule, consisting of two 2-(2'-hydroxyphenyl) benzimidazole (HBI) halves, has been synthesized and successfully utilized as a ratiometric fluorescence sensor for the sensitive detection of Cu based on enol-keto excited-state intramolecular proton transfer (ESIPT). In this study, we strategically implement femtosecond stimulated Raman spectroscopy and several time-resolved electronic spectroscopies, aided by quantum chemical calculations to investigate the detailed primary photodynamics of the BBM molecule. The results demonstrate that the ESIPT from BBM-enol* to BBM-keto* was observed in only one of the HBI halves with a time constant of 300 fs; after that, the rotation of the dihedral angle between the two HBI halves generated a planarized BBM-keto* isomer in 3 ps, leading to a dynamic redshift of BBM-keto* emission.
Topics: Models, Molecular; Protons; Isomerism; Benzimidazoles
PubMed: 37298391
DOI: 10.3390/ijms24119438 -
Magnetic hysteresis and large coercivity in bisbenzimidazole radical-bridged dilanthanide complexes.Chemical Science May 2023A judicious combination of radical ligands innate to diffuse spin orbitals with paramagnetic metal ions elicits strong magnetic exchange coupling which leads to...
A judicious combination of radical ligands innate to diffuse spin orbitals with paramagnetic metal ions elicits strong magnetic exchange coupling which leads to properties important for future technologies. This metal-radical approach aids in effective magnetic communication of especially lanthanide ions as their 4f orbitals are contracted and not readily accessible. Notably, a high spin density on the donor atoms of the radical is required for strong coupling. Such molecules are extremely rare owing to high reactivity rendering their isolation challenging. Herein, we present two unprecedented series of bisbenzimidazole-based dilanthanide complexes [(Cp*Ln)(-Bbim)] (1-Ln = Gd, Tb, Dy, Bbim = 2,2'-bisbenzimidazole) and [K(crypt-222)][(Cp*Ln)(μ-Bbim˙)] -(2-Ln = Gd, Tb, Dy), where the latter contains the first Bbim˙ radical matched with any paramagnetic metal ion. The magnetic exchange constant for 2-Gd of = -1.96(2) cm suggests strong antiferromagnetic Gd-radical coupling, whereas the lanthanides in 1-Gd are essentially uncoupled. calculations on 2-Tb and 2-Dy uncovered coupling strengths of -4.8 and -1.8 cm. 1-Dy features open hysteresis loops with a coercive field of of 0.11 T where the single-molecule magnetism can be attributed to the single-ion effect due to lack of coupling. Excitingly, pairing the effective magnetic coupling with the strong magnetic anisotropy of Dy results in magnetic hysteresis with a blocking temperature of 5.5 K and coercive field of 0.54 T, ranking 2-Dy as the second best dinuclear single-molecule magnet containing an organic radical bridge. A Bbim species is formed electrochemically hinting at the accessibility of Bbim-based redox-active materials.
PubMed: 37265712
DOI: 10.1039/d3sc01562a -
Polymers May 2023Polyimide (PI) with ultra-high thermal resistance and stability is essential for application as a flexible substrate in electronic devices. Here, the Upilex-type...
Polyimide (PI) with ultra-high thermal resistance and stability is essential for application as a flexible substrate in electronic devices. Here, the Upilex-type polyimides, which contained flexibly "twisted" 4,4'-oxydianiline (ODA), have achieved various performance improvements via copolymerization with a diamine containing benzimidazole structure. With the rigid benzimidazole-based diamine bearing conjugated heterocyclic moieties and hydrogen bond donors fused into the PI backbone, the benzimidazole-containing PI showed outstanding thermal, mechanical, and dielectric performance. Specifically, the PI containing 50% bis-benzimidazole diamine achieved a 5% decomposition temperature at 554 °C, an excellent high glass transition temperature of 448 °C, and a coefficient of thermal expansion lowered to 16.1 ppm/K. Meanwhile, the tensile strength and modulus of the PI films containing 50% mono-benzimidazole diamine increased to 148.6 MPa and 4.1 GPa, respectively. Due to the synergistic effect of rigid benzimidazole and hinged, flexible ODA, all PI films exhibited an elongation at break above 4.3%. The electrical insulation of the PI films was also improved with a dielectric constant lowered to 1.29. In summary, with appropriate mixing of rigid and flexible moieties in the PI backbone, all the PI films showed superior thermal stability, excellent flexibility, and acceptable electrical insulation.
PubMed: 37242916
DOI: 10.3390/polym15102343 -
Antimicrobial Agents and Chemotherapy May 2023Clostridioides difficile infection (CDI) causes substantial morbidity and mortality worldwide with limited antibiotic treatment options. Ridinilazole is a precision...
Clostridioides difficile infection (CDI) causes substantial morbidity and mortality worldwide with limited antibiotic treatment options. Ridinilazole is a precision bisbenzimidazole antibiotic being developed to treat CDI and reduce unacceptably high rates of infection recurrence in patients. Although in late clinical development, the precise mechanism of action by which ridinilazole elicits its bactericidal activity has remained elusive. Here, we present conclusive biochemical and structural data to demonstrate that ridinilazole has a primary DNA binding mechanism, with a co-complex structure confirming binding to the DNA minor groove. Additional RNA-seq data indicated early pleiotropic changes to transcription, with broad effects on multiple C. difficile compartments and significant effects on energy generation pathways particularly. DNA binding and genomic localization was confirmed through confocal microscopy utilizing the intrinsic fluorescence of ridinilazole upon DNA binding. As such, ridinilazole has the potential to be the first antibiotic approved with a DNA minor groove binding mechanism of action.
Topics: Humans; Anti-Bacterial Agents; Clostridioides difficile; Pyridines; Clostridium Infections
PubMed: 37093023
DOI: 10.1128/aac.01563-22 -
Frontiers of Optoelectronics Apr 2023Single perylene diimide (PDI) used as a non-fullerene acceptor (NFA) in organic solar cells (OSCs) is enticing because of its low cost and excellent stability. To...
Single perylene diimide (PDI) used as a non-fullerene acceptor (NFA) in organic solar cells (OSCs) is enticing because of its low cost and excellent stability. To improve the photovoltaic performance, it is vital to narrow the bandgap and regulate the stacking behavior. To address this challenge, we synthesize soluble perylenetetracarboxylic bisbenzimidazole (PTCBI) molecules with a bulky side chain at the bay region, by replacing the widely used "swallow tail" type alkyl chains at the imide position of PDI molecules with a planar benzimidazole structure. Compared with PDI molecules, PTCBI molecules exhibit red-shifted UV-vis absorption spectra with larger extinction coefficient, and one magnitude higher electron mobility. Finally, OSCs based on one soluble PTCBI-type NFA, namely MAS-7, exhibit a champion power conversion efficiency (PCE) of 4.34%, which is significantly higher than that of the corresponding PDI-based OSCs and is the highest PCE of PTCBI-based OSCs reported. These results highlight the potential of soluble PTCBI derivatives as NFAs in OSCs.
PubMed: 37087536
DOI: 10.1007/s12200-023-00063-6