In this study, three series of quinazolinone derivatives containing hydrazone structures were designed and synthesized. Bioactivity assays indicated that these compounds showed good antitumour ...activities towards human lung cancer cells (A549) and human prostate cancer cells (PC-3) and no apparent toxicity towards those nontumorigenic rat renal tubular epithelial cells (NRK-52E). In particular, compound
7n
showed potent inhibitory activity towards A549 and PC-3 with IC
50
of 7.36 and 7.73 μmol L
−1
, respectively. Subsequently, the relationships between the compound structures and numerous biological activities are discussed. A good predictive three-dimensional quantitative structure-activity relationship (3D-QSAR) model was constructed
via
CoMFA to direct the future structural units. The present results strongly show that
7n
with the introduction of 2-fluorobenzoyl should be considered as a lead compound to develop novel antitumour agents.
A series of novel quinazolinone derivatives containing hydrazone structural units were synthesized and their antitumour activities were evaluated.
•Near baseline separation for 15 sulfonamides and metabolites by UHPSFC was achieved.•Stationary phases, modifiers, additives, column temperature, ABPR backpressure and flow rate were optimized for ...baseline separate 15 sulfonamides.•UHPSFC-PDA for determination 15 sulfonamides and metabolites in serum.•Simple, accurate, green, low cost, faster separations and better resolution.•Assumed that the retention behavior of sulfonamides on BEH column may mainly depend on the molecule polarity.
An analytical method based on ultra-high performance supercritical fluid chromatography (UHPSFC) with photo-diode array detection (PDA) has been developed to quantify 15 sulfonamides and their N4-acetylation metabolites in serum. Under the optimized gradient elution conditions, it took only 7min to separate all 15 sulfonamides and the critical pairs of each parent drug and metabolite were completely separated. Variables affecting the UHPSFC were optimized to get a better separation. The performance of the developed method was evaluated. The UHPSFC method allowed the baseline separation and determination of 15 sulfonamides and metabolites with limit of detection ranging from 0.15 to 0.35μg/mL. Recoveries between 90.1 and 102.2% were obtained with satisfactory precision since relative standard deviations were always below 3%. The proposed method is simple, accurate, time-saving and green, it is applicable to a variety of sulfonamides detection in serum samples.
A series of new sorafenib derivatives was designed and synthesized. The antiproliferative activity of the synthesized compounds against human lung cancer cell (A549), human pancreatic cancer cell ...(PC‐3), human leukemia cell (K562), and human hepatoma cell (SMMC‐7721) was evaluated by MTT assay. The results revealed that several compounds displayed more significant antitumor activities than commercial anticancer agent sorafenib against SMMC‐7721. In addition, compounds 7a, 7g, 7l, 7m, and 7p represented obvious growth inhibition with IC50 values of 1‐9 μM against four cancer cell lines, demonstrating more predominant activities against cancer cells as compared to sorafenib. Furthermore, some structure‐activity relationships have also been established. Compounds containing indole and benzene ring substituted by halogen showed better activity than sorafenib. Wound healing assay suggested that cells would be targeted on their migratory capacity by 7g, potentially affecting the migration activity of these tumors. The effects of A549 and PC‐3 cell apoptosis induced by compound 7g were significantly increased compared with sorafenib. Importantly, the result of western blot assay showed that 7g inhibited cell growth by suppressing the activity of EGFR, especially the expression of p‐EGFR (Tyr1068).
The novel coronavirus 2019 (COVID-19) pandemic represents one of the biggest global health threats in the last two decades, so researchers around the world are searching for solutions and treatments ...for COVID-19. At the time of writing, there are no specific drugs that have demonstrated suitable effectiveness in treating COVID-19. The current challenge involves designing tools for the prevention, rapid and accurate diagnosis, drug delivery, and effective treatment of this novel coronavirus. In this short review, we discuss how nanotechnology offers new ways to combat COVID-19, and how nanomaterials can be applied to control the COVID-19 outbreak. We also summarize relevant studies regarding the use of nanomaterials for preventing viral spread, preparing vaccines, and diagnosing coronavirus, as well as studies that show how nanoparticles can be used as drug delivery systems for the treatment of viral infections. Research on nanotechnology-based diagnosis, drug delivery, and antiviral therapy is currently in the early stages. However, the unique chemical properties of some nanomaterials highlight the broad prospect of nanomaterials in the future, and we propose that they will play an important role in the fight against COVID-19.
Graphical abstract
(group A
GAS) is an important human pathogen causing a broad spectrum of diseases and associated with significant global morbidity and mortality. Almost all GAS isolates express a surface hyaluronic ...acid capsule, a virulence determinant that facilitates host colonization and impedes phagocyte killing. However, recent epidemiologic surveillance has reported a sustained increase in both mucosal and invasive infections caused by nonencapsulated GAS, which questions the indispensable role of hyaluronic acid capsule in GAS pathogenesis. In this study, we found that pilus of M4 GAS not only significantly promotes biofilm formation, adherence, and cytotoxicity to human upper respiratory tract epithelial cells and keratinocytes, but also promotes survival in human whole blood and increased virulence in murine models of invasive infection. T4 antigen, the pilus backbone protein of M4 GAS, binds haptoglobin, an abundant human acute-phase protein upregulated upon infection and inflammation, on the bacterial surface. Haptoglobin sequestration reduces the susceptibility of nonencapsulated M4 GAS to antimicrobial peptides released from activated neutrophils and platelets. Our results reveal a previously unappreciated virulence-promoting role of M4 GAS pili, in part mediated by co-opting the biology of haptoglobin to mitigate host antimicrobial defenses.
Group A
(GAS) is a strict human pathogen causing more than 700 million infections globally each year. The majority of the disease-causing GAS are encapsulated, which greatly guarantees survival and dissemination in the host. Emergence of the capsule-negative GAS, such as M4 GAS, in recent epidemiologic surveillance alarms the necessity to elucidate the virulence determinants of these pathogens. Here, we found that M4 pili play an important role in promoting M4 GAS adherence and cytotoxicity to human pharyngeal epithelial cells and keratinocytes. The same molecule also significantly enhanced M4 GAS survival and replication in human whole blood and experimental murine infection. T4 antigen, which composes the backbone of M4 pili, was able to sequester the very abundant serum protein haptoglobin to further confer M4 GAS resistance to antibacterial substances released by neutrophils and platelets.
New series of 18 compounds were synthesized using sorafenib derivatives as parent structure and p‐aminoacetophenone as raw materials. The structures of the newly synthesized compounds were confirmed ...on the basis of 1H, 13C NMR and HRMS (Supporting Information). Their antitumor activities against human lung adenocarcinoma cells A549 (A549), prostate cancer cells PC‐3 (PC‐3), human chronic myeloid leukemia cells (K562), and human liver cancer cells (HepG2) in vitro were evaluated, using Sorafenib as a positive control drug. Bioactivity assays indicated that these compounds showed good antitumor activities toward tested four cancer cell lines. In particular, compound 7n showed potent inhibitory activity with IC50 of 7.39 ± 1.51 μM toward K562. The mechanism and the apoptosis inducing effect of 7n against k562 cell line were studied. The results showed that compound 7n blocked K562 cells in G2/M phase to induce cell apoptosis with a concentration and time‐dependent manner.
New series of 18 compounds were synthesized using sorafenib derivatives as parent structure and p‐aminoacetophenone as raw materials. Bioactivity assays indicated that these compounds showed good antitumor activities toward tested four cancer cell lines. The results showed that compound 7n blocked K562 cells in G2/M phase to induce cell apoptosis with a concentration and time dependent manner.
•HPLC-ESI–MS/MS for determination of crocin, crocetin and geniposide .•Novel, simple, rapid, better resolution and low limits of quantitation•Fragment ions were determined upon MS/MS at different ...energies.•Crocin, crocetin and geniposide were determined in real samples.
A novel, rapid and simple analytical method was developed for the quantitative determination of crocin, crocetin and geniposide in soft drink, pastry and instant noodles. The solid samples were relatively homogenized into powders and fragments. The gardenia yellow colorants were successively extracted with methanol using ultrasound-assisted extraction. The analytes were quantitatively measured in the extracts by liquid chromatography coupled with electrospray ionization tandem mass spectrometry. High correlation coefficients (r2>0.995) of crocin, crocetin and geniposide were obtained within their linear ranges respectively (50–1000ng/mL, 50–1000ng/mL, 15–240ng/mL) by external standard method. The limits of detection (LODs) were 0.02μg/g for crocin, 0.01μg/g for crocetin and 0.002μg/g for geniposide. And the limits of quantitation (LOQs) were in the ranges of 0.05–0.45μg/g for crocin, and in the ranges of 0.042–0.32μg/g for crocetin, and in the ranges of 0.02–0.15μg/g for geniposide in soft drink, pastry and instant noodles samples. The average recoveries of crocin, crocetin and geniposide ranged from 81.3% to 117.6% in soft drink, pastry and instant noodles. The intra- and inter-day precisions were respectively in the range of 1.3–4.8% and 1.7–11.8% in soft drink, pastry and instant noodle. The developed methods were successfully validated and applied to the soft drink, pastry, and instant noodles collected from the located market in Beijing from China. Crocin, crocetin and geniposide were detected in the collected samples. The average concentrations ranged from 0.84 to 4.20mg/g for crocin, and from 0.62 to 3.11mg/g for crocetin, and from 0.18 to 0.79mg/g for gardenia in various food samples. The method can provide evidences for government to determine gardenia yellow pigments and geniposide in food.
The differential diagnosis for hereditary ataxia encompasses a variety of diseases characterized by both autosomal dominant and recessive inheritance. There are no curative treatments available for ...these neurodegenerative conditions. This open label treatment study used human umbilical cord blood-derived mononuclear cells (CBMC) combined with rehabilitation training as potential disease modulators.
30 patients suffering from hereditary ataxia were treated with CBMCs administered systemically by intravenous infusion and intrathecally by either cervical or lumbar puncture. Primary endpoint measures were the Berg Balance Scale (BBS), serum markers of immunoglobulin and T-cell subsets, measured at baseline and pre-determined times post-treatment.
A reduction of pathological symptoms and signs was shown following treatment. The BBS scores, IgG, IgA, total T cells and CD3+CD4 T cells all improved significantly compared to pre-treatment values (P < 0.01~0.001). There were no adverse events.
The combination of CBMC infusion and rehabilitation training may be a safe and effective treatment for ataxia, which dramatically improves patients' functional symptoms. These data support expanded double blind, placebo-controlled studies for these treatment modalities.
PDF
