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Chalcone is a common simple fragment of natural products with anticancer activity. In a previous study, the research group discovered a series of chalcone derivatives with stronger anticancer activities. To find better anticancer drugs, novel chalcone derivatives A1–A14, B1–B14 have continuously been designed and synthesized. The antiproliferative activity of these compounds against breast cancer cells (MCF-7) was investigated by the Cell Counting Kit-8 (CCK-8) method with 5-fluorouracil (5-Fu) as the control drug. The results showed that compound A14 exhibited excellent antiproliferative ability compared to the control drug 5-Fu. Scratch experiments and cloning experiments further confirmed that compound A14 could inhibit the proliferation and colony formation activity of MCF-7 cells. In addition, molecular docking primarily explains the interaction between compound and protein. These results suggested that compound A14 could be a promising chalcone derivative for further anti-breast cancer research. [ABSTRACT FROM AUTHOR]

[Display omitted] Chalcone, a common chemical scaffold of many naturally occurring compounds, has been widely used as an effective template for drug discovery due to its broad biological activities. In this study, a series of chalcone derivatives were designed and synthesized based on the hybridization of 1-(2,4,6-trimethoxyphenyl)butan-1-one with chalcone. Interestingly, most of the target compounds exhibited inhibitory effect of tumor cells in vitro. Especially, (E)-3-(5-bromopyridin-2-yl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one (B3) revealed over 10-fold potency than 5-fluorocrail against the Hela and MCF-7 cells with IC 50 values of 3.204 and 3.849 μM respectively. Moreover, B3 displayed low toxicity on normal cells. Further experiments indicated that B3 effectively inhibited the proliferation and migration of tumor cells, and promoted their apoptosis. The calculation and prediction of ADME showed that the target compounds may have good pharmacokinetic properties and oral bioavailability. Reverse molecular docking suggested that the possible target of B3 is CDK1. Taken together, these results suggested that B3 appears to be a promising candidate that merits further attention in the development of anticancer drugs. [ABSTRACT FROM AUTHOR]

Among gynecological tumors, cervical cancer (CC) has the second‐highest prevalence and mortality rate. α‐Pinene is a bicyclic monoterpenoid compound extracted from pine needles that carried promising anticancer properties. Nevertheless, its effect on CC and the underlying mechanism has not yet been elucidated. Therefore, we investigated the effect of α‐Pinene on apoptosis in CC via in vitro assays of flow cytometry (FCW), terminal deoxynucleotidyl transferase‐mediated nick end labeling (TUNEL) assay, quantitative real‐time polymerase chain reaction (qRT‐PCR), and Western blot. Following that, we detected the proapoptotic function of α‐Pinene on HeLa cells in vivo by TUNEL assay and immunofluorescence staining. Our results displayed that the α‐Pinene inhibited the growth of HeLa cells and stalled the cells in the G0/G1 phase. Interestingly, we also detected that α‐Pinene induced HeLa cells to apoptosis. The results investigated that α‐Pinene induced HeLa cells apoptosis along with up‐regulating the expression of Bax, Bid, caspase‐9, caspase‐3, miR‐34a‐5p, and down‐regulating the expression of Bcl‐2 in vitro. At the same time, the expression levels of target genes in vivo were consistent with those in vitro. Our experiment proved that α‐Pinene promoted apoptosis, which will be used to hopefully maximize the therapeutic strategies in clinical studies in CC. [ABSTRACT FROM AUTHOR]

Globally, wound infection is considered to be one of the major healthcare problems, with bacterial infections being the most critical threat, leading to poor and delayed wound healing, and even death. As a superbug, methicillin-resistant Staphylococcus aureus (MRSA) causes a profound hazard to public health safety, prompting us to search for alternative treatment approaches. Herein, the MTT test and Hoechst/propidium iodide (PI) staining demonstrated that PD was slightly less toxic to human fibroblasts including Human keratinocytes (HaCaT) cell line than Silver sulfadiazine (SSD), and Vancomycin (Van). In the MRSA-infected wound model, PD hydrogel (1%, 2.5%) was applied with for 14 days. The wound healing of PD hydrogel groups was superior to the SSD, Van, and control groups. Remarkably, the experimental results showed that PD reduced the number of skin bacteria, reduced inflammation, and upregulated the expression of PCNA (keratinocyte proliferation marker) and CD31 (angiogenesis manufacturer) at the wound site by histology (including hematoxylin–eosin (HE) staining, Masson staining) and immunohistochemistry. Additionally, no toxicity, hemocompatibility or histopathological changes to organs were observed. Altogether, these results suggested the potential of PD hydrogel as a safe, effective, and low toxicity hydrogel for the future clinical treatment of MRSA-infected wounds. [ABSTRACT FROM AUTHOR]

A series of imidazopyrazine derivatives were synthesized, and evaluated for their anti‐inflammatory activity in vitro and in vivo using RAW264.7 cells model and Zebrafish Traumatic Infection Inflammation model. The results in vitro showed that the compounds had significant inhibitory effect on inflammatory factor interleukin 6 (IL6), and N‐ (3 ‐(4‐ ((1,1‐dioxidothiomorpholino) methyl)phenyl) imidazo [1,5‐a] pyrazin‐6‐yl) cyclopropanecarboxamide A1 the best activity, which was significantly different from that of the lipopolysaccharide (LPS) control group (P<0.03). The experiment of anti‐inflammatory activity in vivo indicated that compound A1 showed obvious aggregation inhibitory activity on inflammatory effector cells which was significantly different from that in the tail‐cutting control group (P<0.03). When the concentration of the compound was 160 μg/mL, the inhibitory activity of compound A1 was better than that of dexamethasone positive control group (P<0.05). This study could supply some anti‐inflammatory leading structure and possible mechanism for studying and developing new anti‐inflammatory agents. [ABSTRACT FROM AUTHOR]

Bicyclic phloroglucinol is a phenolic compound which mainly exist in Dryopteris fragrans (L.) Schott with antiinflammatory, antithrombotic, antifungal and antitumor activity. Although a series of anticancer agents target various tumors under clinical trials, different limitations hinder their clinical development and novel targeting chemical agents are required. Herein, we have made a number of modifications around the scaffold of the phloroglucinol. The results of antitumor activities reveal that compound A5 against A549 cells and compound A3 against HepG2 and McF‐7 cells were best with a degree of concentration dependence, which stronger than that of positive control 5‐FU, and compound A3 and A5 display lower cytotoxicity to normal cells. The molecule docking studies indicate protein Bcl‐xl and Mcl‐12 may be a potential target of these compounds. In general, A3 and A5 with potent binding affinity and good efficacy have the potential to develop into antitumor lead compounds which also deserve further study. [ABSTRACT FROM AUTHOR]

Neratinib is an oral pan HER inhibitor, that irreversibly inhibits EGFR and HER2 and was proven to be effective against multiple EGFR mutations. In previous study, we reported spiro [indoline-3, 4′-piperidine]-2-ones as anticancer agents. In this study, we designed aminopyridine-containing spiro [indoline-3,4′-piperidine] derivatives A1-A4 using Neratinib and spiro [indoline-3, 4′-piperidine]-2-one compound patented as lead structure, then replaced piperidine with cyclopropane to obtain B1-B7 and replaced indoline with benzmorpholine to get C1-C4 and D1-D2. We synthesized these compounds and evaluated their residual activities under 0.5 M drug concentration on EGFR and ERBB2. Most of compounds showed stronger inhibition on EGFR-wt and ERBB2, in which A1-A4 showed excellent inhibitory activity with inhibition percentage on EGFR-wt kinase of 7%, 6%, 19%, 27%, respectively and 9%, 5%, 12%, 34% on ERBB2 kinase compared with 2% and 6% of Neratinib. [ABSTRACT FROM AUTHOR]

In the current investigation, total phenols and flavonoids contents of Eleutherine bulbosa (Mill.) Urb. bulbs, leaves, and flowers were quantified by Folin–Ciocalteu's and borohydride/chloroquinone methods, respectively. Antioxidant activity of the plant extracts was evaluated by means of peroxide scavenging capacity assay and by cell antioxidation method. Antioxidant activity of E. bulbosa bulbs, leaves, and flowers was correlated with total phenols and flavonoids. The total phenols and flavonoids of the bulbs of E. bulbosa were higher than leaves and flower and its antioxidant activity was also stronger than leaves and flowers of E. bulbosa. The higher content of flavonoids or total phenols, the stronger the antioxidant capacity in vitro. The antioxidant activity of E. bulbosa extract showed it's certain nutritional value and therefore had the potential as a source of natural antioxidants. Total phenolic, flavonoid content of Eleutherine bulbosa were quantified. Antioxidation of E. bulbosa was correlated with total phenols content and flavonoids. The total phenols or flavonoids was higher and antioxidation was also stronger. Antioxidation of flowers was more valuable than bulbs and leaves. [ABSTRACT FROM AUTHOR]

In this study a variety of phloroglucinols were isolated from the plant, and the activity experiment showed that the phloroglucinols had strong antifungal activity, especially methylphloroglucinol derivatives such as aspidin PB, dryofragin, aspidinol, aspidin BB, aspidin AB, and albicanol, in which the hydroxyl group of methylphloroglucinol is the active group of compounds, and C-2 or C-6 is the active site. The introduction of different groups in this position could change the properties and bioactivity of the compounds. In this study, different functional groups were introduced to the structure of methylphloroglucinol to obtain methylphloroglucinol derivatives that were synthesized, and antidermatophyte activities on Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis , and Gypsum microspore bacteria were evaluated. Molecular docking verified its ability to combine the protein binding site. The antidermatophyte mechanism of compounds on cytochrome P450 sterol 14a-demethylase, squalene epoxidase, and β-1,3-glucan synthase was investigated by the enzyme-linked immunosorbent assay. The results showed that compounds had an inhibitory effect on four kinds of common dermatophytes in varying degrees, in which compound g had the strongest activities, the binding mode of methylphloroglucinol and its derivatives were similar to those of three enzymes, and compounds e and g had significant effects on the activity of the three enzymes, and compound g had a slightly stronger effect than the blank group. Compounds e and g also had a significant effect on the ergosterol synthesis of M. canis. This study could supply some antidermatophyte leading structure and possible mechanism for studying and developing new antifungal agents. [ABSTRACT FROM AUTHOR]

In this paper, a specific design strategy targeting c-met kinase was reported based on docking modeling and topomer comparative molecular field analysis (Topomer CoMFA). A novel U-shape conformation which is distinct from the literature was demonstrated by molecular docking among 68 U-shape c-met inhibitors. According to the docking results, two Topomer CoMFA models with high predictive ability were established based on the two fragment rule. The results from both docking and topomer CoMFA showed that the π-π stacking interaction with Tyr1230 and the hydrogen bond with hinge region play an important role in inhibitory activity. Furthermore, the flexible linker and the adjacent solvent group would be favorable to stabilize the conformation and to enhance the two interactions mentioned above. Based on our patent, 14 new compounds were designed by our design strategy. The binding mode exhibited as expected and their activities were predicted by topomer CoMFA model. The preliminary biological tests showed most of them have potent activity to c-met kinase. Our study would provide guidelines to design some new U-shaped c-met inhibitors with new scaffolds and optimize the current molecules. [ABSTRACT FROM AUTHOR]

Since deregulation of the tyrosine-kinase receptor c-Met is implicated in several human cancers and is an attractive target for small-molecule-drug discovery, we report herein the synthesis of 2,3,4,5-tetrahydro-8-[1-(quinolin-6-ylmethyl)-1 H-1,2,3-triazolo[4,5- b]pyrazin-6-yl]-1 H-pyrido[4,3- b]indoles 4a- 4c and 2,3,4,5-tetrahydro-8-[3-(quinolin-6-ylmethyl)-1,2,4-triazolo[4,3- b]pyridazin-6-yl]-1 H-pyrido[4,3-b]indoles 5a- 5c. These indole derivatives demonstrated inhibition of c-Met kinase activity. Concurrently, five key intermediates were synthesized. These compounds could be prepared in good yields. [ABSTRACT FROM AUTHOR]

Pseudoaspidinol is a phloroglucinol derivative with Antifungal activity and is a major active component of Dryopteris fragrans. In our previous work, we studied the total synthesis of pseudoaspidinol belonging to a phloroglucinol derivative and investigated its antifungal activity as well as its intermediates. However, the results showed these compounds have low antifungal activity. In this study, in order to increase antifungal activities of phloroglucinol derivatives, we introduced antifungal pharmacophore allylamine into the methylphloroglucinol. Meanwhile, we remained C1–C4 acyl group in C-6 position of methylphloroglucinol using pseudoaspidinol as the lead compound to obtain novel phloroglucinol derivatives, synthesized 17 compounds, and evaluated antifungal activities on Trichophyton rubrum and Trichophyton mentagrophytes in vitro. Molecular docking verified their ability to combine the protein binding site. The results indicated that most of the compounds had strong antifungal activity, in which compound 17 were found to be the most active on Trichophyton rubrum with Minimum Inhibitory Concentration (MIC) of 3.05 μg/mL and of Trichophyton mentagrophytes with MIC of 5.13 μg/mL. Docking results showed that compounds had a nice combination with the protein binding site. These researches could lay the foundation for developing antifungal agents of clinical value. [ABSTRACT FROM AUTHOR]