MOLECULES
·
2022
·Vol. 27
·期 5
·1537
·
IF 4.927
Juan Ma,Guo-Hua Gong
In this paper, a small series of novel quinoline sulfonamide derivatives was synthesized, and their structure of the target compounds were confirmed by 1H NMR and MS. The screening of the news target compounds’ in vitro cytotoxic activities against tumor cell lines by the MTT method was performed. Among them, compoundD13(N-(4-methoxybenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide exhibited the strongest inhibitory effect on the proliferation of HeLa (IC50: 1.34 μM), and this value correlated well with the inhibitory activities of the compound against tubulin polymerization (IC50: 6.74 μM). In summary, a new type of quinoline-sulfonamide derivative with tubulin polymerization inhibitory activity was discovered, and it can be used as a lead compound for further modification.Keywords:synthesis;quinoline-sulfonamide;anti-tumor;tubulin polymerization
研究领域:
药物化学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Foods
·
2022
·Vol. 11
·期 13
·1839
·
IF 5.561
Qiao Yang,Xiaoyi Zhang,Huini Qin,Feijun Luo,Jiali Ren
Cancer is still the leading cause of death across the world, and there is a lack of efficient therapies.Lactarius hatsudakeis a mushroom with a food and medicine homology that contains numerous biologically active substances. This study aimed to investigate the composition of extracts fromLactarius hatsudake(L. hatsudake) and their anti-cancer function and molecular mechanisms. Our results showed that the total phenolic content ofL. hatsudakeextracts was 139.46 ± 5.42 mg/g. The following six phenolic compounds were identified fromL. hatsudakeextracts by HPLC and UPLC-QTOF/MS: gallic acid, pyrogallol, chlorogenic acid, ferulic acid, myricetin, and cinnamic acid. Colorectal cancer cell HCT116 and hepatic cancer cell HepG2 were used to evaluate the anti-cancer function of theL. hatsudakeextracts. Compared with HepG2 cells, theL. hatsudakeextracts showed stronger anti-cancer activity against HCT116 cells and these were used to study molecular mechanisms. The results indicated that theL. hatsudakeextracts could arrest the cancer cell cycle and inhibit cancer cell proliferation, which may be mediated by the MAPK/NFκB/AP-1 signalling pathway; theL. hatsudakeextracts also promoted cancer cell apoptosis through a mitochondrial-dependent pathway. Taken together, these findings demonstrate thatL. hatsudakeethanol extracts contain six main phenolics and illustrate the remarkable potentiality ofL. hatsudakeas a source of natural phenolics for cancer prevention and as an adjuvant in the treatment of functional foods.Keywords:Lactarius hatsudake;phenolic acids;anti-cancer;molecular mechanism
研究领域:
药用真菌学
·
肿瘤生物学
·
植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Fang Pan,Yueping Li,Yujie Ding,Songwei Lv,Rongrong You,Roja Hadianamrei,Mhd Anas Tomeh,Xiubo Zhao
Anticancer peptides (ACPs) have attracted increasing attention in cancer therapy due to their unique mechanism of action on cancer cells. The main challenge is to establish the correlation between their physicochemical properties and their selectivity and anticancer effect, leading to a clear design strategy. In this study, a series of new α-helical short peptides (coded At1-At12) with different anticancer activities were systematically designed with different amphiphilicity based on a natural α-helical antimicrobial peptide (AMP) derived from ant. Three of the designed peptides, At7, At10 and At11, showed considerable anticancer activity with low toxicity to normal skin fibroblasts. The high selectivity of the peptides is attributed to their balanced amphiphilicity and cationic nature which favours binding to the outer membrane of negatively charged cancer cells over the neutral membrane of normal mammalian cells . In addition to rapid membrane penetration, the designed peptides also damaged the mitochondria and induced mitochondrial membrane depolarization. Moreover, these peptides were found to induce apoptosis in cancer cells by up-regulating the expression of apoptotic proteins Bax and Caspase-3, down-regulating the apoptotic protein Bcl-2, and activating the Caspase enzyme-linked reaction. The results of this study reveal the potential of these peptides for clinical applications, and provide a guidance for further development of highly selective anticancer medications.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Canadian Journal of Chemistry
·
2016
·Vol. 94
·期 6
·
IF 1.003
Yafei Guo,Jiuling Li,Yuqi Liu,Yongping Ma,Huilin Cheng,Bo Yang,Dandan Liu,Rui Yang
This article describes the preparation of a series of inclusion complexes of anhydrolycorine with three cyclodextrins (CDs), namely β-CD, γ-CD, and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), and their successful characterization through UV, TG, DSC, XRD, SEM, 1H NMR, and 2D NMR spectroscopies. The results demonstrated that the water solubility of anhydrolycorine increased notably by about 23–42 times after the inclusion complexation with these CDs. Furthermore, preliminary in vitro cytotoxicity experiments on human colon cancer cell lines HT-29, SW480, HCT116, and DLD-1 were also performed, and the complexes showed remarkable anticancer activity against HT-29, SW480, and HCT116. These results suggested that the inclusion complexes would be potentially useful for applications for human colon cancer chemotherapy.
研究领域:
药学
·
肿瘤学
·
有机化学
✓ 已验证
DOI
高影响因子
PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
·
2021
·Vol. 38
·期 7
·2100062
·
IF 3.31
Pengfei Yang,Zhihuan Zhao,Shasha Yang,Jianying Lin,Jimin Fan,Bing Zhang
In this study, a chemotherapy-photothermal synergistic anti-tumor system is constructed. Both W 18 O 49 @R-C and PEG-W 18 O 49 @R-C synthesized by hydrothermal method show the potential of photothermal therapy (PTT). The structure of reflux-carbon is bubble-like spherical and W 18 O 49 @R-C obtained by hydrothermal synthesis will cause bubble collapse due to the formation of crystal W 18 O 49 ; thus, the particle size decreases sharply. Furthermore, the photothermal stability of PEG-W 18 O 49 @R-C is higher than that of W 18 O 49 @R-C, and ζ-potential measurement indicates that PEG-W 18 O 49 @R-C has excellent dispersion characteristics. The test of drug loading and drug release performance show that PEG-modified W 18 O 49 @R-C has superior performance on drug loading amount and release capacity. In the synergistic anti-tumor process, the cancer cell viability after co-incubating with PEG-W 18 O 49 @R-C+DOX . HCl (with 808nm) is only 16.6%. These results indicate that PEG-W 18 O 49 @R-C has potential in the treatment of cancer by a combination of PTT and chemotherapy.
研究领域:
肿瘤学
·
材料科学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
IUBMB LIFE
·
2019
·Vol. 71
·期 7
·1014-1020
·
IF 3.051
Yanbin Su,Chengyu Sun,Yan Chen,Shichang Liu,Ning Jing,Shuxin Li
The aim of this study was to explore how the toxic trans -crotonaldehyde (TCA) in mitochondria or aldehyde dehydrogenase (ALDH) at different pHs was intercepted by oxyresveratrol (Oxy-Res) contributing to anticancer. Ultraviolet–visible (UV–vis) spectroscopy and Raman spectroscopy were employed. UV–vis spectra showed that the Oxy-Res red shifted the peak of the toxic TCA from 316 nm to 325 nm, while the peaks of the Oxy-Res shifted from 329 nm with 290 nm and 300 nm to 325 nm with 303 nm. In the mitochondria, the Oxy-Res blue shifted the peaks of the toxic TCA from 325 nm with 303 nm to 321 nm with 301 nm. Raman spectra revealed that the Oxy-Res caused shifting of the CHO of the toxic TCA from 1,689 cm −1 to 1,671 cm −1 with band decline. The CC of the toxic TCA at 1641 cm −1 was split into 1,639 cm −1 and 1,642 cm −1 with band decline. The bands of the Oxy-Res at 1634 cm −1 , 1,617 cm −1 , and 1,595 cm −1 disappeared. In the mitochondria, the CC of the toxic TCA at 1641 cm −1 splitting disappeared. In ALDH, with the decrease of pH from 7.8 to 6.5, the CHO of the toxic TCA did not red shift from 1,689 cm −1 to 1,674 cm −1 up to pH 6.5. There was no change in the CC of the toxic TCA at 1640 cm −1 in ALDH at different pHs. The conclusion of the study was that the CHO of the toxic TCA was intercepted by the Oxy-Res under the action of ALDH in the mitochondria, particularly at pH 7.8. © 2019 IUBMB Life, 2019
研究领域:
生物化学
·
医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2020
·Vol. 13
·期 10
·2706-2715
·
IF 8.183
Yan Jing,Zhu Rongying,Wu Fan,Zhao Ziyin,Ye Huan,Hou Mengying,Liu Yong,Yin Lichen
Insufficient intratumoral penetration greatly hurdles the anticancer performance of nanomedicine. To realize highly efficient tumor penetration in a precisely and spatiotemporally controlled manner, far-red light-responsive nanoclusters (NCs) capable of size shrinkage and charge conversion were developed and co-administered with iRGD to synergistically improve the intratumoral penetration and the anticancer efficacy. The NCs were constructed using the singlet oxygen-sensitive (SOS) polyethylene glycolpolyurethane-polyethylene glycol (PEG-( 1 O 2 )PU-PEG) triblock copolymer to encapsulate the doxorubicin (DOX)-loaded, chlorin e6 (Ce6)-conjugated polyamindoamine (PAMAM) dendrimer (DCD) via the double-emulsion method. Co-administration of iRGD notably increased the permeability of NCs within tumor vasculature and tumor tissues. In addition, upon far-red light irradiation (660 nm) of tumors at low optical density (10 mW/cm 2 ), the generated 1 O 2 could disintegrate the NCs and release the DCD with positive surface charge and ultra-small size (∼5 nm), which synergized with iRGD to enable deep intratumoral penetration. Consequently, the local 1 O 2 at lethal concentrations along with the released DOX efficiently and cooperatively eradicated tumor cells. This study provides a convenient approach to spatiotemporally promote the intratumoral penetration of nanomedicine and mediate programmed anticancer therapy.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2015
·Vol. 38
·期 10
·1658-1662
·
IF 1.828
Lu-yang Lu,Yuan Liu,Zhi-feng Zhang,Xiao-jun Gou,Jun-hao Jiang,Ji-zhong Zhang,Qian Yao
Pomegranate seed oil (PSO) has diverse bioactivities. It was hyphothesized that if PSO were employed to construct a trans-resveratrol-loaded self-nanoemulsifying drug delivery system (RES SNEDDS-PSO), not only could PSO serve as an oil phase but also exert synergistic effects with resveratrol to yield better therapeutic outcomes. In this study, we prepared RES SNEDDS-PSO for the first time to validate that hypothesis. The anti-inflammatory and anticancer activities of RES SNEDDS-PSO were compared with another SNEDDS composed of oil phase isopropyl palmitate (RES SNEDDS-IP). The results showed that upon exposure to a 10-fold amount of water, RES SNEDDS-PSO was converted into nanoemulsions with a mean size of 44 nm. Nanoemulsions enhanced the water solubility of resveratrol by 20-fold, significantly improved resveratrol stability in intestinal fluid, and slowed the decomposition of resveratrol in water by 1-fold. An in vivo anti-infection test showed that the degree of inflammatory swelling in mice given RES SNEDDS-PSO was only 60 and 76% that of the group fed with RES SNEDDS-IP at doses of 10 and 20 mg/kg, respectively. An in vitro anticancer study showed that the inhibitory rate of RES SNEDDS-PSO against MCF-7 breast cancer cells was 2.03- and 1.24-fold that of RES SNEDDS-IP at a concentration of 12.5 and 25 µg/mL, respectively. This study demonstrated that the newly developed SNEDDS may be a prospective formulation in the functional food and clinical fields.
研究领域:
药剂学
·
生物医学
·
食品科学
✓ 已验证
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2013
·Vol. 42
·期 27
·9852-9861
·
IF 3.806
Yuan Wu,Dongmei Yang,Xiaojiao Kang,Ping'an Ma,Shanshan Huang,Yang Zhang,Chunxia Li,Jun Lin
Multifunctional nanocomposites integrating mesoporous and luminescence properties into a single entity are synthesized via a facile and effective approach. Oleic acid capped β-NaYF4:Ce3+/Tb3+ nanoparticles (NPs) are transferred into aqueous solution by cetyltrimethylammonium bromide (CTAB) surfactants, and further encapsulated with uniform mesoporous silica shell followed by the surface modification with poly(ethylene glycol) (PEG), leading to the formation of water-dispersible and biocompatible core–shell structured β-NaYF4:Ce3+/Tb3+@mSiO2-PEG (denoted as NPs@mSiO2-PEG) nanospheres. The as-synthesized nanospheres show a typical mesoporous structure and a green emission under UV irradiation. Doxorubicin hydrochloride (DOX), a widely used anti-cancer drug, is used as a model drug to evaluate the loading and controlled release behaviors of the NPs@mSiO2-PEG in phosphoric acidic buffer solutions (PBS) at different pH values (pH = 7.4 and 5.0). The composite carriers provide a pH-sensitive drug release pattern and the drug releases faster under lower pH value. The endocytosis process of fluorescein isothiocyanate (FITC)-labelled nanospheres is characterized using flow cytometry and confocal laser scanning microscopy (CLSM) against A549 cells. The in vitro cytotoxic effect against A549 cells of the DOX-loaded carriers is investigated in detail. In addition, the extent of drug release can be monitored by the variation of photoluminescence (PL) intensity of β-NaYF4:Ce3+/Tb3+. Considering the good biocompatibility and pH-dependent drug release pattern, such core–shell structured luminescent NPs@mSiO2-PEG nanospheres have potential applications in controlled drug delivery.
研究领域:
生物材料
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2021
·
IF 5.275
Zhiwen Qi,Guliang Yang,Tao Deng,Jianmin Wang,Hao Zhou,Sergey A. Popov,Elvira E. Shults,Chengzhang Wang
Ursolic acid (UA) is an accessible triterpenoid, widely applied in the design and synthesis of antitumor compounds. However, the mechanism of its anti-tumor effect is still unclear. To verify the molecular mechanism of its biological activity, based on the bifunctional activity of ubiquitination and subsequent proteasomal degradation of the target protein of the proteolysis-targeting chimeras (PROTACs) strategy, here we report the design, synthesis and cellular activity of six UA PROTAC hydrochloride compounds 1A - 1F , in which UA acts as the binding ligand of the PROTAC and is linked to thalidomide (E3 ligand) through a series of synthetic linkers. The results revealed that compound 1B , connected with a POE-3 (3-Polyoxyether) possessed remarkable in vitro antitumor activity (with the IC 50 value of 0.23 ~ 0.39 μM against A549, Huh7, HepG2). WB results demonstrated that the administration of compound 1B induced significant degradation of MDM2 (only 25% to that of SM1), and promoted the expression of P21 and PUMA proteins, and thus inhibited the proliferation (77.67% of 1B vs 60.37% of CON in G1 phase) and promoted the apoptosis (26.74% of 1B vs 3.35% of CON) of A549 cells. This work demonstrated proof of designing the efficient target protein degradation by UA PROTACs with the POE linkers. In addition, we confirmed that UA possess the characteristic of targeted-binding the protein of murine double minute-2 protein (MDM2). This will lay a foundation for the comprehensive utilization of forest natural compound UA.
研究领域:
药理学
·
肿瘤学
·
化学生物学
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2015
·
IF 4.074
Xuejing Jia,Chao Zhang,Jianfeng Qiu,Lili Wang,Jiaolin Bao,Kai Wang,Yulin Zhang,Meiwan Chen,Jianbo Wan,Huanxing Su,Jianping Han,Chengwei He
Three novel acidic polysaccharides termed PRM1, PRM3 and PRM5 were purified from Rhynchosia minima root using DEAE-52 cellulose and sephadex G-150 column chromatography. Their structures were characterized by ultraviolet (UV) and Fourier transform infrared (FTIR) spectrometry, gel permeation chromatography (GPC), gas chromatography–mass spectrometry (GC–MS), and differential scanning colorimeter (DSC) analysis. The uronic acid contents of PRM1, PRM3 and PRM5 were 30.7%, 12.7% and 47.7%, respectively. PRM1 (143.2 kDa), PRM3 (105.3 kDa) and PRM5 (162.1 kDa) were heteropolysaccharides because they were composed of arabinose, mannose, glucose and galactose. Their enthalpy values were 201.0, 111.0 and 206.8 J/g, respectively. PRM3 and PRM1 exhibited strong in vitro anticancer activity against lung cancer A549 and liver cancer HepG2 cells in a dose-dependent manner. These findings suggested that PRM1 and PRM3 could be potentially developed as natural anticancer agents.
研究领域:
植物化学
·
药理学
·
肿瘤学
✓ 已验证
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2019
·
IF 2.12
Xue-Pu Feng,Xin Na,Ya-Fei Guo,Rui Qian,Jian-Qiang Zhang,Zhen Chen,Rui Yang
1, 2-O, O-Diacetyllycorine (DALY) is one of the lycorine derivatives which has various biological properties. However, the bioavailability and clinical application of DALY was restrained because of its low water solubility and moderate antitumor activities . In order to improve its physicochemical properties, we prepared the inclusion complex of DALY with α-cyclodextrin (α-CD). The inclusion complex was characterized by UV, XRD, DSC , TG, 1 H, 2D NMR spectroscopy and its anticancer activity was evaluated in vitro against the human cell lines HCT116, A549, HepG2 and K562. The results demonstrated that DALY was encapsulated into the cavity of α-CD to form the complexes with 1:1 stoichiometry . The water solubility of DALY significantly increased for about 49 times after the inclusion complexation with α-CD. Furthermore, the cytotoxicity of DALY/α-CD against the examined cell lines was significantly increased for about 80 times compared to that of the free DALY. The improved physicochemical and biological properties of the inclusion complexes will be beneficial for its potential applications in the design and formulation of natural medicines.
研究领域:
药学
·
肿瘤学
·
天然药物化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）