SYNTHETIC COMMUNICATIONS
·
2023
·
IF 2.1
Jun Yang,Guang-Ping Liang,Xiong-Li Liu
To investigate the effects and mechanisms of 4-(1H-indol-1-yl)-4-oxobutanoic acid spliced podophyllotoxin derivatives (3a–3l) on tumor cells. The MTT method was adopted to evaluate (3a–3l) antitumor activity in vitro against A549 cells, A549/DDP cells, MCF-7 cells. The results showed that compound 3l had the most prominent inhibitory effect and high selectivity with IC50 18.53 ± 1.51 µM against A549/DDP cells. Meanwhile, the effects of compound 3l on the nuclear state, cell cycle and apoptosis of A549/DDP cells showed that compound 3l induced apoptosis by delaying the G2/M phase of A549/DDP cell cycle. In addition, molecular docking of compound 3l also showed that it could form a good hydrogen bond with ARG-158 (d = 2.6, 2.7 Å) and HIS-406 (d = 2.5 Å) at the colchicine site of tubulin. Compound 3l could provide lead compound for the development of new multi-drug resistant anti-tumor drugs.
研究领域:
药理学
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肿瘤学
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化学
·
分子生物学
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产品关联
DOI
高影响因子
Drug Design Development and Therapy
·
2017
·
IF 2.822
Jingrun Chen,Junjie Liu,Dongxiao Cui,Chaoqun Yan,Liqiang Meng,Liqian Sun,Shurong Ban,Rui Ge,Taigang Liang,Qingshan Li
This study deals with the design and synthesis of a series of novel 4-methoxy-substituted and 5-methyl-substituted (3′S,4′S)-(−)-cis-khellactones. The newly synthesized compounds were characterized by 1H nuclear magnetic resonance (NMR), 13C-NMR, mass spectrometry, and elemental analysis. All the derivatives were subjected to in vitro cytotoxicity screening against HEPG-2 (human liver carcinoma), SGC-7901 (human gastric carcinoma), and LS174T (human colon carcinoma), by using the MTT assay. The results revealed that several of the 4-methoxy-substituted compounds exhibited potent cytotoxicity. Among these, compound 12e showed the highest activity against cancer cells which 50% inhibitory concentration (IC50) values were in the range of 6.1–9.2 μM with low toxicity on normal human hepatocyte. Preliminary investigation of possible mechanisms of action of compound 12e against HEPG-2 cells indicated possible induction of apoptosis, as determined by morphological observations and Annexin V/propidium iodide (PI) double staining, in addition to apparent dissipation of mitochondrial membrane potential (MMP), as measured by 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1) staining in combination with the activation of caspase-9 and caspase-3 by Western blot analysis. Overall, the data suggest that compound 12e may be a promising potential anti-cancer agent that could act primarily by inducing apoptosis through the mitochondria-mediated intrinsic pathway in human hepatoma cells.
研究领域:
药理学
·
肿瘤学
·
药物化学
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DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2024
·
IF 8.1
Xin Liang,Sheng Wang,Jing Zhou,Tengfei Lu,Kaiyu Ruan,Yuqian Xia,Tong Wang
Despite the considerable attention received by switchable solvents in natural product extraction and biorefinery. To tackle this issue, the present study has the following innovative endeavors: (1) Developing an innovative high-speed homogenization assisted extraction method using the DES/SHS/H 2 O system and applying it to the integrated extraction of phenolics, flavonoids, and essential oil from Flos Chrysanthemi Indici . The switching process was characterized using 1 H NMR, the extraction process was optimized employing response surface methodology, the components of extracted essential oils were analyzed by GC–MS, and the cytotoxicity and anti-inflammatory activity of essential oils were determined through MTT and ELISA. Our findings demonstrate that the incorporation of DES can significantly augment the CO 2 switching kinetics of SHS, resulting in a 32.7 % reduction in switching time and a remarkable decrease of 73.7 % residual content within the aqueous phase. The innovative DES/SHS/H 2 O based extraction method exhibited substantial enhancements in phenolics, flavonoids, and essential oil extraction efficiency compared to conventional approaches, yielding extracts with superior chemical profiles and enhanced anti-inflammatory activity. Therefore, the proposed strategy of enhancing the CO 2 switching kinetic properties and extraction ability of SHS by incorporating DES is feasible, providing valuable guidance for the rational design of innovative smart solvent systems. The developed DES/SHS/H 2 O system, exhibiting improved performance, holds significant application and research prospects.
研究领域:
化学工程
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药学
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分析化学
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生物技术
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天然产物研究
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产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Li Shaoguang,Wang Xuewen,Wang Gang,Shi Peiying,Lin Shilan,Xu Dafen,Chen Bing,Liu Ailin,Huang Liying,Lin Xinhua,Yao Hong
Colorectal cancer is one type of cancer with high incidence rate and high mortality worldwide. Thus, developing new chemotherapeutic drugs is important. The Selaginella doederleinii Hieron ethyl acetate (SDEA) extract showed good anti-colon cancer effect in vitro and in vivo, but its mechanism is unclear. This study aimed to further reveal the anti-colon cancer effect of SDEA and its possible mechanism. The effects on cell viability, apoptosis, autophagy, and cell cycle in colorectal cells (HT29 and HCT116) were studied using MTT assay, fluorescence microscopy, transmission electron microscopy, and flow cytometry. The mechanisms were further studied using cell transfection, Western blot, and real-time quantitative polymerase chain reaction assay. The effect of xenotransplantation in vivo was observed using immunohistochemistry. Results showed that SDEA inhibited cell proliferation and induced cell morphological changes, cell cycle arrest, autophagy, and apoptosis. It also induced loss of mitochondrial membrane potential, increased the autophagic flux, raised the ratio of Bax/Bcl-2, activated caspases, and inhibited PI3K-Akt-mTOR signaling pathways. Furthermore, SDEA inhibited the growth of xenograft tumors in a dose-dependent manner. Immunohistochemistry analysis confirmed the alteration of autophagy- and apoptosis-related proteins and immunohistochemical microvascular density in xenografts, which were consistent with the results in vitro. Therefore, SDEA is important for developing candidate drugs against colorectal cancers.
研究领域:
肿瘤学
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药理学
·
细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 73
·45978-45986
·
IF 3.108
Na Wen,Chunmei Gao,Shaoyu Lü,Xiubin Xu,Xiao Bai,Can Wu,Piao Ning,Shaofei Zhang,Mingzhu Liu
The high pKa (8.26 to 8.6) of PBA has restricted its glucose-responsiveness in physiological conditions, and the high cytotoxicity of polymers is also a limiting problem in their potential application for insulin delivery. Novel amphiphilic glucose-sensitive dialdehyde starch polymers containing 3-aminophenylboronic acid (APBA) as a glucose-responsive group and mPEGylated dialdehyde starch (mPEG-DAS) with hydrophobic 7-hydroxycoumarin-4-acetic acid (Cou) were synthesized. This dialdehyde starch derivative can self-assemble into mPEG-DAS–APBA–Cou micelles with “shell–core” structures in phosphate-buffered saline solution (PBS). In addition, the drug-loaded micelles can release insulin rapidly in response to hyperglycemia in a physiological environment. The results demonstrated that the mPEG-DAS–APBA–Cou micelles showed notable glucose responsive behavior near the physiological range. The insulin release from the nanocarriers is sensitive to different concentrations of glucose, releasing insulin rapidly under the conditions of 3 mg mL−1 glucose while demonstrating comparatively inert release at 1 mg mL−1 glucose (pH 7.4). MTT assays and hemolysis studies both confirmed that the mPEG-DAS–APBA–Cou micelles have low cytotoxic activity to A549 cells and low blood toxicity. These results suggest that the glucose-sensitive dialdehyde starch micelles (mPEG-DAS–APBA–Cou) have potential applications as a glucose-responsive material for insulin delivery.
研究领域:
药学
·
纳米技术
·
生物材料
·
药物递送系统
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 5
·期 5
·1108-1116
·
IF 4.872
Zhe Yang,Jinghua Ren,Zhilan Ye,Wei Zhu,Liji Xiao,Li Zhang,Qianyuan He,Zushun Xu,Haibo Xu
Polypyrrole nanoparticle (PPy) based theranostic agents for magnetic resonance imaging (MRI) guided photothermal therapy (PTT) have received increasing attention in recent years. However, the limitations of cost and biocompability still offer us opportunities to improve these agents. Considering the versatile character of polydopamine (PDA), PEGylated PPy@Fe3+-chelated PDA nanocomposites (PPDEs) were designed and prepared in an easy way. PPDE with a uniform core–shell structure could be obtained by adjusting the ratio of dopamine and PPys. In this nanocomplex, the shells confer the nanoparticles with good biocompability and MRI signal enhancing ability. Moreover, the PPy cores play a role in photothermal ablation of tumors. Compared with pure PDA nanoparticles, the PPDEs have higher NIR absorbance and better photothermal capability benefitting from the high photothermal conversion of the cores. Additionally, the obtained PPDEs provide significant MRI signal enhancement for both in vitro and in vivo imaging with high longitudinal relaxivity (r1 = 5.055 mM−1 s−1). After intravenous injection, the PPDEs exhibited valid tumor accumulation, as revealed by MRI and verified by biodistribution analysis. Under NIR irradiation, the PPDEs showed highly effective photothermal ablation of 4T1 cells. Notably, excellent biocompability of the PPDEs was confirmed by a relevant MTT assay and histologic analysis. This work achieved an example of exploiting the inherent advantages of PPy and PDA within a single unit and exploring its potential for T1 MRI-guided PTT.
研究领域:
材料科学
·
生物医学工程
·
纳米技术
·
癌症治疗
·
磁共振成像
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2023
·Vol. 28
·期 2
·1-11
·
IF 3.4
Qiao Lu,Xueyang Gong,Guangtao Jia,Jingliang Wu,Siwei Liu,Ke Song,Guixiang Tian
All‑trans retinoic acid (ATRA) has been implicated in the differentiation of hepatic stellate cells (HSCs). In the present study, the liver‑targeting hyaluronic acid micelles (ADHG) were prepared for co‑delivery of ATRA and doxorubicin (DOX) to block the HSC‑hepatoma interrelation. To simulate the tumor microenvironment, an in vitro dual‑cell model and an in vivo co‑implantation mouse model were established for anticancer studies. The experimental methods involved the MTT assay, wound‑healing assay, cellular uptake, flow cytometry and and in vivo antitumor study. The results revealed that the HSCs in the research models notably promoted tumor proliferation and migration. Furthermore, ADHG were readily internalized by cancer cells and HSCs simultaneously, and widely distributed in cancer regions. The in vivo antitumor studies demonstrated that ADHG could notably decrease HSC activation and extracellular matrix deposition, as well as constrain tumor growth and metastasis. Therefore, ATRA could facilitate DOX‑induced anti‑proliferation and anti‑metastasis effects, and ADHG are a promising nano‑sized formulation for the combination therapy of hepatocellular carcinoma.
研究领域:
药理学
·
肿瘤学
·
纳米技术
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Jiuheng Ruan,Chao Liu,Jiaqi Wang,Ting Zhong,Peng Quan,Liang Fang
This study sought to provide approach for evaluating and predicting the efficacy and safety of permeation enhancers on the basis of their kinetic distribution behavior in the skin dictated by physicochemical properties. Herein, the efficacy-safety regularity of eight permeation enhancers were studied with ex vivo skin permeation study, small-angle X-ray scattering, MTT assay, H&E staining, and in vivo skin erythema analysis, classifying into the following three categories: high enhancement–low irritation, medium enhancement–high irritation, and low enhancement–low irritation. These three modes were positively correlated with the distribution amount of permeation enhancers in the skin layers and verified by the in vitro tape-stripping study. The kinetic parameter, effective-safety index ( I ES ), was proposed to describe the regularity of enhancement effect tendency and irritation risk, and the relationship between I ES and physicochemical properties of permeation enhancers was analyzed with multiple regression analysis. According to the results of modulated temperature differential scanning calorimetry and dielectric spectrum, permeation enhancers with high lipophilicity and low polarity had I ES > 1, suggesting high enhancement effect and low irritation due to their higher affinity with the stratum corneum (SC) than with epidermis (EP). Permeation enhancers with medium lipophilicity and medium polarity exhibited 0 < I ES ≤ 1, showing medium enhancement effect and high irritation, as determined by their comparable affinity with the SC and epidermis (EP). However, permeation enhancers with low lipophilicity and high polarity had I ES → 0, demonstrating low enhancement effect and irritation, as indicated by their poor affinity with the SC. In summary, different physicochemical properties of permeation enhancers influenced their affinities with skin layers, resulting in their different enhancement effect and irritation potential. This study will provide a theoretical basis and criteria for evaluating and predicting the safety and efficacy of permeation enhancers, which will enable a more rational selection of permeation enhancers in the optimization of transdermal patches .
研究领域:
药剂学
·
药理学
·
生物物理学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2023
·
IF 3.4
Xueqiang Sun,Fuxin Li,Lingyan Yuan,Zhitong Bing,Xun Li,Kehu Yang
Resveratrol (Res) is known for its potential in treating various types of cancers, with a particular advantage of causing minimal toxic side effects. However, its clinical application is constrained by challenges such as poor bioavailability, low water solubility, and chemical instability in neutral and alkaline environments. In light of these limitations, we have developed a pH-responsive drug delivery nanoplatform, Res@ZIF-8/TA NPs, which exhibits good biocompatibility and shows promise for in vitro cancer therapy. Benefiting from the mild reaction conditions provided by zeolitic imidazolate frameworks (ZIFs), a “one-pot method” was used for drug synthesis and loading, resulting in a satisfactory loading capacity. Notably, Res@ZIF-8/TA NPs respond to acidic environments, leading to an improved drug release profile with a controlled release effect. Our cell-based experiments indicated that tannic acid (TA) modification enhances the biocompatibility of ZIFs. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT assay), Hoechst 33342/PI staining, cell scratch assay, Transwell and Reverse Transcription quantitative PCR (RT-qPCR) assays further demonstrated that Res@ZIF-8/TA NPs inhibited colon cancer cell migration and invasion, and promoted apoptosis of colon cancer cells, suggesting a therapeutic potential and demonstrating anti-cancer properties. In conclusion, the Res@ZIF-8/TA NPs pH-responsive drug delivery systems we developed may offer a promising avenue for cancer therapy. By addressing some of the challenges associated with Res-based treatments, this system could contribute to advancements in cancer therapeutics.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2025
·
IF 3.1
Wu Xinhua,Wu Lifang,Li Zhaoquan,Tian Wei,Li Tao
Three series of (dimethyl-, dibutyl-, and diphenyl-) new organotin(IV) complexes based on chlorine substituted aryl ligands were synthesized and characterized by UV, 1 H NMR, 13 C NMR, 119 Sn NMR, HRMS, and X-ray crystallography analysis. MTT results showed that chlorine substitution at different positions on the aryl group exhibited different anticancer activities. Among them, 5-chloro substituents > 3,5-dichloro substituents > 3-chloro substituents on the aryl ring of salicylaldehyde on Schiff base ligand. In addition, different substituents on the tin atom also demonstrated extreme differences in anticancer activities, where dibutyltin > diphenyltin > dimethyltin. Interestingly, the complex LTDB2 exhibited excellent anti-proliferative activity against breast cancer MDA-MB-231 cells (superior to cisplatin) and lower toxicity against human embryonic kidney HEK-293 cells in vitro. Flow cytometry showed that LTDB2 not only induced apoptosis, but also induced cell cycle arrest in G2 phase. These findings provide new insights for further research and development of novel organotin(IV) complexes as anticancer drugs. Complex LTDB2 exhibited excellent anti-proliferative activity against breast cancer MDA-MB-231 cells in vitro and was superior to cisplatin. Flow cytometry showed that LTDB2 not only induced apoptosis, but also induced cell cycle arrest in G2 phase.
研究领域:
化学
·
药理学
·
肿瘤学
·
材料科学
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DOI
高影响因子
Natural Product Communications
·
2020
·
IF 0.468
Ling-Li Zheng,Guan Wen,Yun-Xin Yao,Xiao-Huan Li,Feng Gao
Based on the strong activity dependence of paclitaxel (PTX; Taxol) or docetaxel (Taxotere) on the C-13 side chain, a small library of dehydroepiandrosterone, cholesterol, vitamin D2, and alkaloids talatisamine and songorine-PTX hybrids have been synthesized and evaluated for in vitro anticancer activity by MTT assay against human breast (MCF-7), colon (HCT116), lung carcinoma (A549), and renal adenocarcinoma (786-0) cancer cell lines. Most hybrids (11b, 12b, 13b, 15b, and 18b) reduced the growth of MCF-7 and 786-0 cells with low PTX sensitivity in vitro. Among the synthesized compounds, hybrid 11b was better in inhibiting the growth of the 4 cells than PTX. A relatively low IC50 value of compound 11b (8.16 ± 0.04 μM) was also examined after exposure for 48 hours. Hybrid 11b showed a proapoptotic effect in HCT116 cells evaluated by Annexin V/propidium iodide binding assay. The level of hybrid 11b leading to protective cell death in HCT116 cells was detected using western blot and not easily observed in our basic examinations.
研究领域:
药理学
·
肿瘤学
·
药物化学
·
细胞生物学
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产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2020
·
IF 5.115
Haiyan Wang,Qiuping Xu,Hui Hu,Chunling Shi,Ziyan Lin,Huixi Jiang,Huaipu Dong,Jing Guo
Background Relying on surface topography alone to enhance the osteointegration of implants is still inadequate. An effective way to combine long-term ion release and surface topography to enhance osteogenic property is urgently needed. Purpose The objective of this study is to fabricate a long-term strontium ion release implant system and confirm the biological function in vitro and in vivo. Methods The biomimic surface was fabricated through alkali-heat treatment and magnetron sputtering. The in vitro biological function assays were determined by MTT, fluorescence staining, alkaline phosphatase activity, extracellular mineralization, and quantitative real-time polymerase chain reaction assays. The in vivo experiments were detected by micro-CT, HE staining and Masson staining. Results The biomimic surface structure has been successfully fabricated. The in vitro cell assays determined that AH-Ti/Sr90 possessed the best biological function. The in vivo experiments demonstrated that AH-Ti/Sr90 could promote osteointegration significantly under both in normal and osteoporotic conditions. Conclusion We determined that AH-Ti/Sr90 possesses the best osteogenic property, long-term ion release capacity and osteointegration promotion ability. It has potential clinic application prospects.
研究领域:
生物材料
·
生物医学工程
·
骨科
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）