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51.
Rosane Bassi Soares Denis Honorato Costa Walter Miyakawa Maria Goretti Temoteo Delgado Aguinaldo Silva Garcez Tania Mateus Yoshimura Martha Simões Ribeiro Silvia Cristina Nunez 《Photochemistry and photobiology》2020,96(3):618-624
Ventilator-associated pneumonia (VAP) is an infection that arises after endotracheal intubation affecting patients under intensive care. The presence of the endotracheal tube (ETT) is a risk factor since it is colonized by multispecies biofilm. Antimicrobial photodynamic therapy (aPDT) could be a strategy to decontaminate ETTs. We verify if methylene blue (MB) associated with external illumination of the ETT could be an alternative to destroy biofilm. We performed an in vitro and ex vivo study. In vitro study was performed with P. aeruginosa biofilm grew over ETT for 7 days. After treatment, the surviving cells were cultured for 3 days and the biofilm was analyzed by crystal violet absorbance. Ex vivo study employed ETT obtained from extubated patients. aPDT was performed with MB (100 µm ) and red LED (λ = 640±20 nm). We quantified the biofilm thickness and used scanning electron microscopy and fluorescence technique to verify morphological and functional changes after aPDT. Our results showed that bacteria remain susceptible to aPDT after sequential treatments. We also attested that aPDT can reduce biofilm thickness, disrupt biofilm attachment from ETT surface and kill microbial cells. These data suggest that aPDT should be investigated to decrease VAP incidence via ETT decontamination. 相似文献
52.
Svitlana V. Shishkina Igor V. Ukrainets Olga V. Vashchenko Natali I. Voloshchuk Pavlo S. Bondarenko Lidiya A. Petrushova Galina Sim 《Acta Crystallographica. Section C, Structural Chemistry》2020,76(1):69-74
The title benzothiazine‐3‐carboxamide, C17H16N2O4S, crystallized in two enantiomorphic crystal forms with the space groups P32 and P31 despite the absence of a classic stereogenic atom. The molecular structures are mirror images of each other. Only one sulfonyl O atom takes part in intramolecular hydrogen bonding as a proton acceptor and this atom is different in the two enantiomorphic structures. As a result, the S atom becomes a pseudo‐stereogenic centre. This fact is worth taking into account due to the different biological activities of the enantiomorphic forms. One form possesses a high analgesic activity, while the other form revealed a high anti‐inflammatory activity. 相似文献
53.
Sim Woojeong Lee Booyeong Kim Dong Ju Lee Jeong A Kim Jaewon Chung Jintai 《Nonlinear dynamics》2022,108(2):987-1004
Nonlinear Dynamics - This study analyzes the vibro-impact behavior of two adjacent cantilever beams subjected to vibration generated by applying harmonic excitation to their rigid base. For the... 相似文献
54.
Mubashir Hassan Balasaheb D. Vanjare Kyou-Yeong Sim Hussain Raza Ki Hwan Lee Saba Shahzadi Andrzej Kloczkowski 《Molecules (Basel, Switzerland)》2022,27(5)
A series of nine novel 1,2,4-triazole based compounds were synthesized through a multistep reaction pathway and their structures were scrutinized by using spectral methods such as FTIR, LC-MS, 1H NMR, and 13C NMR. The synthesized derivatives were screened for inhibitory activity against the mushroom tyrosinase and we found that all the synthesized compounds demonstrated decent inhibitory activity against tyrosinase. However, among the series of compounds, N-(4-fluorophenyl)-2-(5-(2-fluorophenyl)-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-ylthio) acetamide exhibited more prominent activity when accompanied with the standard drug kojic acid. Furthermore, the molecular docking studies identified the interaction profile of all synthesized derivatives at the active site of tyrosinase. Based on these results, N-(4-fluorophenyl)-2-(5-(2-fluorophenyl)-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-ylthio) acetamide could be used as a novel scaffold to design some new drugs against melanogenesis. 相似文献
55.
Dongjoon Lee Jong-Chan Park Keum Sim Jung Jiyeong Kim Ji Sung Jang Sunghoon Kwon Min Soo Byun Dahyun Yi Gihwan Byeon Gijung Jung Yu Kyeong Kim Dong Young Lee Sun-Ho Han Inhee Mook-Jung 《Experimental & molecular medicine》2022,54(1):61
The deposition of beta-amyloid (Aβ) in the brain precedes the onset of symptoms such as cognitive impairment in Alzheimer’s disease (AD); therefore, the early detection of Aβ accumulation is crucial. We previously reported the applicability of the QPLEXTM Alz plus assay kit for the prescreening of Aβ accumulation. Here, we tested the specific application of the kit in a large cohort of cognitively normal (CN) individuals of varying ages for the early detection of Aβ accumulation. We included a total of 221 CN participants with or without brain Aβ. The QPLEXTM biomarkers were characterized based on age groups (1st–3rd tertile) and across various brain regions with cerebral amyloid deposition. The 3rd tertile group (>65 years) was found to be the most suitable age group for the application of our assay kit. Receiver operating characteristic curve analysis showed that the area under the curve (AUC, discrimination power) was 0.878 with 69.7% sensitivity and 98.4% specificity in the 3rd tertile group. Additionally, specific correlations between biomarkers and cerebral amyloid deposition in four different brain regions revealed an overall correlation with general amyloid deposition, consistent with previous findings. Furthermore, the combinational panel with plasma Aβ1–42 levels maximized the discrimination efficiency and achieved an AUC of 0.921 with 95.7% sensitivity and 67.3% specificity. Thus, we suggest that the QPLEXTM Alz plus assay is useful for prescreening brain Aβ levels in CN individuals, especially those aged >65 years, to prevent disease progression via the early detection of disease initiation.Subject terms: Alzheimer''s disease, Neural ageing, ELISA 相似文献
56.
Eun Kee Cho Phong K. Quach Yunfei Zhang Jae Hun Sim Tristan H. Lambert 《Chemical science》2022,13(8):2418
The use of hydrazine-catalyzed ring-closing carbonyl–olefin metathesis (RCCOM) to synthesize polycyclic heteroaromatic (PHA) compounds is described. In particular, substrates bearing Lewis basic functionalities such as pyridine rings and amines, which strongly inhibit acid catalyzed RCCOM reactions, are shown to be compatible with this reaction. Using 5 mol% catalyst loadings, a variety of PHA structures can be synthesized from biaryl alkenyl aldehydes, which themselves are readily prepared by cross-coupling.Hydrazine catalysis enables the ring-closing carbonyl–olefin metathesis (RCCOM) to form polycyclic heteroaromatics, especially those with basic functionality.Polycyclic heteroaromatic (PHA) structures comprise the core framework of many valuable compounds with a diverse range of applications (Fig. 1A).1 For example, polycyclic azines (e.g. quinolines) are embedded in many alkaloid natural products, including diplamine2 and eupolauramine3 to name just a few. These types of structures are also of interest for their biological activity, such as with the inhibitor of the Src-SH3 protein–protein interaction shown in Fig. 1A.4 Many nitrogenous PHAs are also useful as ligands for transition metal catalysis, as exemplified by the widely used ligand 1,10-phenanthroline.5 Meanwhile, chalcogenoarenes6 such as dinaphthofuran7 and benzodithiophene8 have attracted high interest for both their medicinal properties9 and especially for their potential use as organic light-emitting diodes (OLEDs), organic photovoltaics (OPVs), and organic field-effect transistors (OFETs).10 These and numerous other examples have inspired the development of a wide variety of strategies to construct PHAs.1,11–14 Although these approaches are as varied as the structures they target, the wide range of molecular configurations within PHA chemical space and the challenges inherent in exerting control over heteroatom position and global structure make novel syntheses of these structures a topic of continuing interest.Open in a separate windowFig. 1(A) Examples of PHAs. (B) RCCOM strategy for PHA synthesis. (C) Lewis base inhibition for Lewis acid vs. hydrazine catalyzed RCCOM. (D) Hydrazine-catalyzed RCCOM for PHA synthesis.One potentially advantageous strategy for PHA synthesis is the use of ring-closing carbonyl–olefin metathesis15 (RCCOM) to forge one of the PHA rings, starting from a suitably disposed alkenyl aldehyde precursor 2 that can be easily assembled by cross-coupling (Fig. 1B). In related work, the application of RCCOM to form polycyclic aromatic hydrocarbons (PAHs) was reported by Schindler in 2017.16 In this case, 5 mol% FeCl3 catalyzed the metathesis of substrates to form phenanthrenes and related compounds in high yields at room temperature. This method was highly attractive for its efficiency, its use of an earth-abundant metal catalyst, and the production of benign acetone as the only by-product. Nevertheless, one obvious drawback to the use of Lewis acid activation is that the presence of any functionality that is significantly more Lewis basic than the carbonyl group can be expected to strongly inhibit these reactions (Fig. 1C). Such a limitation thus renders this method incompatible with a wide swath of complex molecules, especially PHAs comprised of azine rings. This logic argues for a mechanistically orthogonal RCCOM approach that allows for the synthesis of PHA products with a broader range of ring systems and functional groups.We have developed an alternative approach to catalytic carbonyl–olefin metathesis that makes use of the condensation of 1,2-dialkylhydrazines 5 with aldehydes to form hydrazonium ions 6 as the key catalyst–substrate association step.17–19 This interaction has a much broader chemoorthogonality profile than Lewis acid–base interactions and should thus be much less prone to substrate inhibition than acid-catalyzed approaches. In this Communication, we demonstrate that hydrazine-catalyzed RCCOM enables the rapid assembly of PHAs bearing basic functionality (Fig. 1D).For our optimization studies, we chose biaryl pyridine aldehyde 7 as the substrate (20 salt 11 was also productive (entry 2), albeit somewhat less so. Notably, iron(iii) chloride generated no conversion at either ambient or elevated temperatures (entries 3 and 4). Trifluoroacetic acid (TFA) was similarly ineffective (entry 5). Meanwhile, a screen of various solvents revealed that, while the transformation could occur in a range of media (entries 6–9), THF was optimal. Finally, by raising the temperature to 90 °C (entry 10) or 100 °C (entry 11), up to 96% NMR yield (85% isolated yield) of adduct 8 could be obtained in the same time period.Optimization studiesa
Open in a separate windowaConditions: substrate 8 (0.2 mmol) and 5 mol% catalyst in 0.4 mL of solvent (0.5 M) in a 5 mL sealed tube were heated to the temperature indicated for 15 h. Yields were determined by 1H NMR using CH2Br2 as an internal standard.b2 equiv. of TFA was used.c85% isolated yield.Using the optimized conditions, we explored the synthesis of various PHAs (Fig. 2). In addition to benzo[h]isoquinoline (8), products 12 and 13 with fluorine substitution at various positions could be generated in good yields. Similarly, benzoisoquinolines 14 and 15 bearing electron-donating methoxy groups and the dioxole-fused product 16 were also accessed efficiently. Furthermore, a phenolic ether product 17 with a potentially acid-labile N-Boc group was generated in modest yield. We found that an even more electron-donating dimethylamino group was also compatible with this chemistry, allowing for the production of 18 in 68% yield. On the other hand, adduct 19 bearing a strongly electron-withdrawing trifluoromethyl group was isolated in only modest yield. The naphtho-fused isoquinoline 20 could be generated as well; however, 20 mol% catalyst was required to realize a 35% yield. The thiophene-fused product 21 was furnished in much better yield, also with the higher catalyst loading. Although not a heterocyclic system, we found that the reaction to form phenanthrene (22) was well-behaved, providing that compound in 83% yield. In addition, an amino-substituted phenanthrene 23 was also formed in good yield. Other thiophene-containing PAHs such as 24–26 were produced efficiently. On the other hand, adduct 27 was generated only in low yield. Naphthofuran (28), which is known to have antitumor and oestrogenic properties,21 was synthesized in good yield. Finally, pharmaceutically important structures such as benzocarbazole2229 and naphthoimidazole2330 could be accessed in moderate yields with increased catalyst loading.Open in a separate windowFig. 2Substrate scope studies for hydrazine 1-catalyzed RCCOM synthesis of polycyclic heteroaromatics. a Conditions: substrate and catalyst 1·(TFA)2 (5 mol%) in THF (0.5 M) were heated to 100 °C in a 5 mL sealed tube for 15 h. Yields were determined on purified products. b 20 mol% catalyst.We also examined the scope of the olefin substitution pattern ( Entry Substrate Time (h) Yield (%) 1 15 96 2 48 5 3b 48 27 4 48 54 5 48 64
Entry | Catalyst | Solvent | Temp. (°C) | 8 yield (%) |
---|---|---|---|---|
1 | 10 | THF | 80 | 67 |
2 | 11 | THF | 80 | 53 |
3 | FeCl3 | DCE | rt | 0 |
4 | FeCl3 | DCE | 80 | 0 |
5 | TFA | THF | 80 | 0b |
6 | 10 | i-PrOH | 80 | 31 |
7 | 10 | CH3CN | 80 | 28 |
8 | 10 | EtOAc | 80 | 26 |
9 | 10 | Toluene | 80 | 24 |
10 | 10 | THF | 90 | 87 |
11 | 10 | THF | 100 | 96c |