scholarly journals Design, Synthesis, Molecular Docking, and Tumor Resistance Reversal Activity Evaluation of Matrine Derivative with Thiophene Structure

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 417
Author(s):  
Jinrui Wei ◽  
Yuehui Liang ◽  
Lichuan Wu
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Southern China ◽  
Synergistic Effects ◽  
Docking Studies ◽  
Tumor Resistance ◽  
Design Synthesis ◽  
Apoptosis Protein ◽  
Resistance Reversal

Nasopharyngeal carcinoma (NPC) frequently occurs in Southern China. The main treatments of NPC are chemotherapy and radiotherapy. However, chemo-resistance arises as a big obstacle in treating NPC. Therefore, there is a great need to develop new compounds that could reverse tumor drug resistance. In this study, eight matrine derivatives containing thiophene group were designed and synthesized. Structures of these 8 compounds were characterized by 1H-NMR, 13C-NMR, and high-resolution mass spectrometer (HRMS). The cytotoxicity and preliminary synergistic effects of these 8 compounds were detected against nasopharyngeal carcinoma (NPC) cells and cisplatin-resistant NPC cells (CNE2/CDDP), respectively. Furthermore, the in vivo and in vitro tumor resistance reversal effects of compound 3f were evaluated. Moreover, docking studies were performed in Bclw (2Y6W). The results displayed that compound 3f showed synergistic inhibitory effects with cisplatin against CNE2/CDDP cells proliferation via apoptosis induction. Docking results revealed that compound 3f may exert its effects via inhibiting anti-apoptosis protein Bcl-w.

scholarly journals Synergistic Effects of Curcumin and Nano-Curcumin against Toxicity, Carcinogenicity, and Oxidative Stress Induced by Tartrazine at Normal and Cancer Cell Levels

Catalysts ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1203
Author(s):  
Gaber E. El-Desoky ◽  
Saikh M. Wabaidur ◽  
Mohamed A. Habila ◽  
Zeid A. AlOthman
Keyword(s):  
Oxidative Stress ◽  
Synergistic Effects ◽  
Economic Benefits ◽  
Cellular Level ◽  
Anticancer Properties ◽  
Antioxidant Defense Enzymes ◽  
Apoptosis Protein ◽  
Nano Formulation

In this study, the cellular synergistic and antagonistic effects of mixing tartrazine (TZ) with curcumin (CUR) or curcumin-nanoparticles (CUR-NPs) were investigated. The in vivo administration of TZ, CUR, CUR-NPs, and TZ mixed with CUR or CUR-NPs at 75:25 or 50:50 ratios were tested. The results indicated that CUR and CUR -NPs reduced the cytotoxicity effects of TZ on skin fibroblast BJ-1 (ATCC® CRL-2522™) normal cells. However, among the tested materials, CUR-NPs had highest in vitro and in vivo antioxidant activity compared to TZ. Furthermore, CUR-NPs and CUR exhibited anticancer activity against HepG-2 liver cancer cells via apoptosis induction. The key apoptosis protein genes Caspase-3, p53, and Bax were upregulated, whereas Bc-2, which exhibits anti-apoptosis activity, was downregulated. Our results indicated that the nano-formulation of CUR alters its physicochemical properties, including the size and shape, and increases its antioxidant and anticancer properties. CUR-NPs also overcome the side effect of using TZ as a yellow color and food preservative additive, due to its reduced toxicity, oxidative stress, and carcinogenicity. In agreement with our previous findings, CUR and CUR-NPs were able to protect against cellular oxidative stress by stimulating endogenous antioxidant defense enzymes, including superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione-S-transferase (GST). We conclude that the nano-formulation of CUR exhibits economic benefits as a new strategy to use CUR as a food additive at the cellular level.

BIX-01294-enhanced chemosensitivity in nasopharyngeal carcinoma depends on autophagy-induced pyroptosis

2020 ◽  
Vol 52 (10) ◽  
pp. 1131-1139
Author(s):  
Qian Li ◽  
Min Wang ◽  
Yan Zhang ◽  
Liuqian Wang ◽  
Wei Yu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Caspase 3 ◽  
Southern China ◽  
Annexin V ◽  
In Vivo Studies ◽  
Cell Swelling ◽  
Chemotherapeutic Drugs ◽  
Double Positive

Abstract Nasopharyngeal carcinoma (NPC) is a common cancer in southern China and Southeast Asia. Nowadays, radiotherapy is the therapy of choice for NPC patients, and chemotherapy has been found as an alternative treatment for advanced NPC patients. However, finding novel drugs and pharmacologically therapeutic targets for NPC patients is still urgent and beneficial. Our study showed that BIX-01294 (BIX) can induce autophagic vacuoles formation and conversion of LC3B-I to LC3B-II in NPC cells in both dose- and time-dependent manners. Notably, the combination of BIX and chemotherapeutic drugs significantly decreased the cell viability and increased the lactate dehydrogenase release. Meanwhile, BIX plus cis-platinum (Cis) treatment induced pyroptosis in NPC cells as featured by cell swelling and bubble blowing from the plasma membrane, the increased frequency of annexin V and propidium iodide (PI) double-positive cells, as well as the cleavage of gasdermin E (GSDME) and caspase-3. Moreover, the deficiency of GSDME completely shifted pyroptosis to apoptosis. Furthermore, the inhibition of autophagy by chloroquine and the knockout of ATG5 gene significantly blocked the BIX-induced autophagy as well as pyroptosis in both in vitro and in vivo studies. Our data demonstrated that BIX-combined chemotherapeutic drugs could induce the Bax/caspase-3/GSDME-mediated pyroptosis through the activation of autophagy to enhance the chemosensitivity in NPC.

scholarly journals AIMP2-DX2 Promotes the Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Qingsong Cao ◽  
Jie Zhang ◽  
Tao Zhang
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Protein Expression ◽  
Southern China ◽  
Immunohistochemical Analysis ◽  
Prognostic Indicator ◽  
Trna Synthetase ◽  
Migration And Invasion ◽  
Induced Apoptosis

Nasopharyngeal carcinoma (NPC) is a head and neck tumor with high degree of malignancy and with high incidence especially in southern China. AIMP2-DX2, one isoform of the aminoacyl-tRNA synthetase interacting multifunctional proteins (AIMPs), is shown to be a potential target in many cancers. However, the detailed mechanisms of AIMP2-DX2 in NPC development remain to be elucidated. Here, we found that the mRNA expression level of AIMP2-DX2 was significantly increased in NPC specimens, compared with normal nasopharyngeal tissues. Microarray immunohistochemical analysis of NPC specimens and Kaplan–Meier analysis showed that patients with high AIMP2-DX2 protein expression had shorter overall survival than those with low AIMP2-DX2 level. Furthermore, mRNA and protein expression levels of AIMP2-DX2 were both increased in cultured NPC cell lines (5-8F, CNE-2Z, and CNE-1), by being compared with normal nasopharyngeal cell line NP69. Overexpression of AIMP2-DX2 remarkably promoted the cell viability, cell migration, and invasion of cultured NPC cells. Genetic knockdown of AIMP2-DX2 by shRNA lentiviruses significantly suppressed the proliferation, migration, and invasion and induced apoptosis of NPC cells. Inhibition of AIMP2-DX2 decreased the highly expressed level of matrix metalloproteinase- (MMP-) 2 and MMP-9, further suppressed proliferation, migration, and invasion in cultured NPC cells in vitro, and inhibited tumor growth in a xenograft mouse model in vivo. Taken together, these results suggest that AIMP2-DX2 plays an important role in the regulation of NPC and could be a potential therapeutic target and prognostic indicator for the treatment of NPC.

scholarly journals Computer-Aided Studies for Novel Arylhydantoin 1,3,5-Triazine Derivatives as 5-HT6 Serotonin Receptor Ligands with Antidepressive-Like, Anxiolytic and Antiobesity Action In Vivo

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2529 ◽  
Author(s):  
Rafał Kurczab ◽  
Wesam Ali ◽  
Dorota Łażewska ◽  
Magdalena Kotańska ◽  
Magdalena Jastrzębska-Więsek ◽  
...  
Keyword(s):  
Serotonin Receptor ◽  
Binding Mode ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Activity Data ◽  
Aromatic Fragment ◽  
Design Synthesis ◽  
Computer Aided

This study focuses on the design, synthesis, biological evaluation, and computer-aided structure-activity relationship (SAR) analysis for a novel group of aromatic triazine-methylpiperazines, with an hydantoin spacer between 1,3,5-traizine and the aromatic fragment. New compounds were synthesized and their affinities for serotonin 5-HT6, 5-HT1A, 5-HT2A, 5-HT7, and dopamine D2 receptors were evaluated. The induced-fit docking (IFD) procedure was performed to explore the 5-HT6 receptor conformation space employing two lead structures. It resulted in a consistent binding mode with the activity data. For the most active compounds found in each modification line, anti-obesity and anti-depressive-like activity in vivo, as well as “druglikeness” in vitro, were examined. Two 2-naphthyl compounds (18 and 26) were identified as the most active 5-HT6R agents within each lead modification line, respectively. The 5-(2-naphthyl)hydantoin derivative 26, the most active one in the series (5-HT6R: Ki = 87 nM), displayed also significant selectivity towards competitive G-protein coupled receptors (6–197-fold). Docking studies indicated that the hydantoin ring is stabilized by hydrogen bonding, but due to its different orientation, the hydrogen bonds form with S5.44 and N6.55 or Q6.58 for 18 and 26, respectively. Compound 26 exerted anxiolytic-like and antidepressant-like activities. Importantly, it demonstrated anti-obesity properties in animals fed palatable feed, and did not show toxic effects in vitro.

scholarly journals Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design, Synthesis, and Investigation of Antinociceptive Potency

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5578
Author(s):  
Kirill P. Cheremnykh ◽  
Victor A. Savelyev ◽  
Sergey A. Borisov ◽  
Igor D. Ivanov ◽  
Dmitry S. Baev ◽  
...  
Keyword(s):  
Lethal Dose ◽  
Experimental Pain ◽  
Binding Mode ◽  
Docking Studies ◽  
Sonogashira Reaction ◽  
Design Synthesis ◽  
Hybrid Molecules ◽  
High Yields

Convenient and efficient routes to construct hybrid molecules containing diterpene alkaloid lappaconitine and pyrimidine fragments are reported. One route takes place via first converting of lappaconitine to 1-ethynyl-lappaconitine, followed by the Sonogashira cross-coupling-cyclocondensation sequences. The other involves the palladium-catalyzed carbonylative Sonogashira reaction of 5′-iodolappaconitine with aryl acetylene and Mo (CO)6 as the CO source in acetonitrile and subsequent cyclocondensation reaction of the generated alkynone with amidines. The reaction proceeded cleanly in the presence of the PdCl2-(1-Ad)2PBn∙HBr catalytic system. The protocol provides mild reaction conditions, high yields, and high atom and step-economy. Pharmacological screening of lappaconitine-pyrimidine hybrids for antinociceptive activity in vivo revealed that these compounds possessed high activity in experimental pain models, which was dependent on the nature of the substituent in the 2 and 6 positions of the pyrimidine nucleus. Docking studies were undertaken to gain insight into the possible binding mode of these compounds with the voltage-gated sodium channel 1.7. The moderate toxicity of the leading compound 12 (50% lethal dose (LD50) value was more than 600 mg/kg in vivo) and cytotoxicity to cancer cell lines in vitro encouraged the further design of therapeutically relevant analogues based on this novel type of lappaconitine–pyrimidine hybrids.

Design, Synthesis, Antioxidant, Anti-inflammatory Activity and Molecular Docking Studies of Novel 3,4,5-Trisubstituted-1,2,4-Triazole Derivatives Bearing Benzimidazole Moiety

2020 ◽  
Vol 17 ◽  
Author(s):  
Ramamurthy Katikireddy ◽  
Ramu Kakkerla ◽  
M.P.S. Murali Krishna ◽  
Gandamalla Durgaiah ◽  
Narasimha Reddy Yellu
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Biological Data ◽  
Inflammatory Activity ◽  
Design Synthesis ◽  
Molecular Docking Studies ◽  
Cox 2 ◽  
Anti Inflammatory

: 5-(7-Methyl-2-propyl-1H-benzo[d]imidazol-5-yl)-4-phenyl-4H-1,2,4-triazole-3-thiols(6a-i) have been synthesized from key intermediate 7-methyl-2-propyl-1H-benzo[d]imidazole-5-carbohydrazide(3). The hydrazide was treated with different aryl isothiocyanatesto give corresponding thiosemicarbazone derivatives, which underwent cyclization in 4N sodium hydroxide to affordcorresponding title compound. All the compounds evaluated for their in vitro antioxidant and in vivo anti-inflammatory activity. From the results, compounds 6b and 6e have shown potential antioxidant and anti-inflammatory activity. The biological data was further supported by molecular docking studies, which revealed the binding pattern and the affinity of the molecules in the active site of COX-2.

scholarly journals Synergistic Effects of Targeting Survivin and CDK1 on Nasopharyngeal Carcinoma <i>in Vitro</i> and <i>in Vivo</i>

2019 ◽  
Vol 10 (04) ◽  
pp. 305-315
Author(s):  
Hongtao Zhou ◽  
Xinping Chen ◽  
Shuping Chen ◽  
Junhong Cai ◽  
Jiye Zhang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Synergistic Effects

scholarly journals Design, Synthesis, Biological Evaluation and Molecular Docking Studies of 5-fluorouracil-dithiocarbamate Conjugates

2022 ◽  
Author(s):  
Yifeng Zhan ◽  
Youyun Wang ◽  
Puzhao Wang ◽  
Hongda Zhu ◽  
Huiling Guo ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Copper Ions ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Cell Cycle Distribution ◽  
Design Synthesis ◽  
Excellent Growth ◽  
Anti Tumor Activity

Abstract In this paper, a series of novel 5-fluorouracil-dithiocarbamate conjugates were designed, synthesized and evaluated in vitro . The results of cytotoxicity assays illuminated that these conjugates had anti-tumor activity against B16, Hela and U87MG, and compound P3 exhibited excellent growth inhibition against U87MG cells. Interestingly, the cytotoxicity of these conjugates was significantly increased when combined with copper ions. Meanwhile, colony-formation assays, transwell migration assays, cell apoptosis assays and cell cycle distribution assays were performed to explore the anti-tumor mechanism of conjugates. Compound P3 and P4 exhibited good biological activity in above four experiments when combined with copper ions. Especially, P3 displayed better bioactivity compared to the other three compounds. These results indicated that conjugates might be metabolized in the cells to produce dithiocarbamates, then metabolites formed complexes with copper ions, generating anti-tumor effects. Furthermore, conjugates and their metabolized dithiocarbamate derivatives were investigated by molecular docking, the results exhibited that P3 had the strongest interaction with the proteins 6CCY and 5T92, which was consistent with the obtained results of cell experiments. Compound P3 might be a potential lead-compound for the treatment of breast cancer and glioma. Further research in vivo about these compounds would be performed in our following work.

Sign in / Sign up

Export Citation Format

Share Document