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Background: Spirocyclic indoline compounds widely exist in numerous natural products and synthetic molecules with significant biological activities. In recent years, these kinds of compounds have attracted extensive attention as potent anti-tumor agents in the fields of pharmacology and chemistry. Objective: In this study, we focused on designing and synthesizing novel 1'-methylspiro[indoline- 3,4'-piperidine] derivatives, which were evaluated by preliminary bioactivity experiment in vitro and molecular docking. Methods and Materials: The key intermediate 1'-methylspiro[indoline-3,4'-piperidine] (B4) reacted with benzenesulfonyl chloride with different substituents under alkaline condition to obtain its derivatives (B5-B10). We evaluated their antiproliferative activities against A549, BEL-7402 and HeLa cell lines by MTT assay. We performed the CDOCKER module in Accelrys Discovery Studio 2.5.5 for molecular docking of compound B5, and investigated the binding modes of compound B5 with three different target proteins. Results: The results indicated that compounds B4-B10 exhibited good antiproliferative activities against the above three types of cell lines, in which compound B5 with chloride atom as electronwithdrawing substituent on a phenyl ring showed the highest potency against BEL-7402 cell lines (IC50=30.03±0.43 μg/mL). The results of molecular docking showed that the binding energies of the prominent bioactive compound B5 with CDK, c-Met, and EGFR protein crystals are -44.3583 kcal/mol, -38.3292 kcal/mol, -33.3653 kcal/mol, respectively. Conclusion: 1'-methylspiro[indoline-3,4'-piperidine] and its six derivatives were synthesized and evaluated against BEL-7402, A 549, and Hela cell lines. Compound B5 showed significant inhibition on BEL-7402 cell lines. Molecular docking assays revealed that B5 as a ligand showed strong affinity and appropriate binding pose on the amino acid residues in active sites of the tested targets, which encourage us to conduct further evaluation such as the kinase experiment.

Purpose α-pinene was a chemical compound which was extracted from pine needles oil, and it exerted effects on various diseases. However, the effect of α-pinene on cervical cancer had not been reported. The goal of this study was to explore the anti-tumor role of α-pinene. Methods Methyl thiazolyl tetrazolium (MTT) method was used to detect cytotoxicity of α-pinene. Flow cytometry was used to quantify the cell cycle and apoptosis. TUNEL staining was also performed for the revalidation of apoptosis. QRT-PCR and western blot was implemented to detect the expression levels of apoptosis genes and miR-34a-5p. Tumor-bearing nude mouse models was adopted to assess the anti-tumor action of α-pinene in vivo. Results The results displayed α-pinene restrained proliferation of Hela cells in G1 phase and induced Hela cell apoptosis, which was related to up-regulating expressions of Bax, Bid, Caspase-9, Caspase-3, miR-34a-5p and down-regulating the expression of Bcl-2. Afterwards, α-Pinene could regulate miR-34a-5p/Bcl-2 pathway. Furthermore, α-pinene treatment also induced apoptosis in xenografts tumor models. The fluorescence intensity of Bax, Bid, Caspase-9, Caspase-3 increased and fluorescence intensity of Bcl-2 decreased. Conclusions Our research demonstrated α-pinene could restrain the development of cervical cancer growth, and it might be an effective chemical compound for therapy of cervical cancer.

Liver fibrosis has the potential to progress into liver cirrhosis, liver failure, and even death. Hepatic stellate cells (HSCs) activation play a central role in liver fibrosis, and persistently damaged hepatocytes secrete soluble factors that activate transdifferentiation of HSCs into myofibroblasts. Our previous studies indicated that fine particulate matter (PM2.5) can activate HSCs by stimulating hepatocytes to secrete TGF-β1. However, whether PM2.5 activates HSCs by regulating oxidative stress in hepatocytes remains uncertain. Oleanolic acid (OA) has been widely used in the clinic for hepatoprotection in Chinese medicine. In the present study, OA-loaded nanoparticles (OA-NP) with high solubility were used to attenuate the activation of HSCs induced by PM2.5-treated hepatocytes, and further studies were performed to explore the mechanism in which OA-NP plays a vital part. Our results showed that consistently PM2.5 treatment induced oxidative stress in hepatocytes. Moreover, the activation of HSCs induced by PM2.5-treated hepatocytes was reversed by antioxidant N-acetylcysteine treatment. Hence, PM2.5 may participate in the activation of HSCs by regulating oxidative stress in hepatocytes. Using a co-cultivation system, our results proved pretreatment with OA-NP significantly attenuates the activation of HSCs induced by PM2.5-exposed hepatocytes. In addition, the TGF-β1 expression and oxidative stress in hepatocytes with PM2.5 treated were reduced by the incubation with OA-NP. These observations demonstrated that OA-NP protects against the activation of HSCs by decreasing the TGF-β1 level and oxidative stress in PM2.5-exposed hepatocytes.

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.

s Pine needle oil from crude extract of pine needles has been used as an anti-cancer agent in Traditional Chinese Medicine. The α-pinene is a natural compound isolated from pine needle oil which has been shown anti-cancer activity. In previous study, we found that pine needle oil exhibited significant inhibitory effect on hepatoma carcinoma BEL-7402 cells. In this study, we investigate the inhibition of α-pinene on hepatoma carcinoma BEL-7402 cells in vitro and in vivo and further explore the mechanism. The results show that liver cancer cell growth was inhibited obviously with inhibitory rate of 79.3% in vitro and 69.1% in vivo , Chk1 and Chk2 levels were upregulated, CyclinB, CDC25 and CDK1 levels were downregulated.