scholarly journals Design and Synthesis of Molecular Hybrids of Sophora Alkaloids and Cinnamic Acids as Potential Antitumor Agents

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1168
Author(s):  
Hai Shang ◽  
Lingyu Li ◽  
Liyan Ma ◽  
Yu Tian ◽  
Hongmei Jia ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cinnamic Acid ◽  
Antitumor Agents ◽  
Human Tumor ◽  
Positive Control ◽  
Potent Effect ◽  
Design And Synthesis ◽  
Lead Compounds ◽  
Molecular Hybrids

Twenty-five sophora alkaloids-cinnamic acid hybrids (including matrine-cinnamic acid hybrids, sophoridine-cinnamic acid hybrids, and sophocarpine-cinnamic acid hybrids) were designed, synthesized, and evaluated in vitro against three human tumor cell lines (HeLa, HepG2 and A549) with cisplatin as a positive control. Some matrine-cinnamic acid and sophoridine-cinnamic acid compounds exhibited potent effect against all three cancer cell lines, such as compounds 5b, 5e, 5g, and 6d. The structure-activity relationship study of the synthesized compounds was also performed. Preliminary mechanistic studies indicated that compounds 5e and 6d could induce apoptosis in HepG2 cell line. Further, compounds 5e and 6d altered mitochondrial membrane potential and produced ROS leading to cell apoptosis of HepG2 cells. Overall, our findings suggested that these compounds may provide promising lead compounds for further development as antitumor agents by structural modification.

scholarly journals Use of 2-aminoprop-1-ene-1,1,3-tricarbonitrile for the synthesis of tetrahydronaphthalene, hexahydroisoquinoline and hexahydrocinnoline derivatives with potential antitumor activities

2011 ◽  
Vol 61 (1) ◽  
pp. 51-62 ◽  
Author(s):  
Rafat Mohareb ◽  
Hosam Moustafa
Keyword(s):  
Cell Lines ◽  
Antitumor Agents ◽  
Human Tumor ◽  
Breast Adenocarcinoma ◽  
Inhibitory Effects ◽  
Antitumor Activities ◽  
Chemical Reagents ◽  
Tumor Types ◽  
Potential Antitumor

Use of 2-aminoprop-1-ene-1,1,3-tricarbonitrile for the synthesis of tetrahydronaphthalene, hexahydroisoquinoline and hexahydrocinnoline derivatives with potential antitumor activities The aim of the work was to synthesize heterocyclic compounds from 2-aminoprop-1-ene-1,1,3-tricarbonitrile and to study their antitumor activities. The title reagent reacted with cyclohexanone to give the ethylidene derivative 2. The reactivity of the latter product towards different chemical reagents was studied to give tetrahydronaphthalene, hexahydroisoquinoline and hexahydrocinnoline derivatives. The newly synthesized products were screened as antitumor agents on the in vitro growth of three human tumor cell lines representing different tumor types, namely, breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268). It was found that some of these compounds showed inhibitory effects on the three cell lines, indicating their potential use in the development of oncology products.

scholarly journals Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives

2016 ◽  
Vol 66 (1) ◽  
pp. 129-137 ◽  
Author(s):  
Paulo H. B. França ◽  
Edeildo F. Da Silva-Júnior ◽  
Pedro G. V. Aquino ◽  
Antônio E. G. Santana ◽  
Jamylle N. S. Ferro ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Human Tumor ◽  
Tetrazolium Salt ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Lead Compounds

Abstract Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L−1 against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

scholarly journals Chemical Composition, Antimicrobial, and Cytotoxic Activities of Leaf, Fruit, and Branch Essential Oils Obtained From Zanthoxylum nitidum Grown in Vietnam

2021 ◽  
Vol 16 (1) ◽  
pp. 1934578X2098564
Author(s):  
Tran Thi Tuyen ◽  
Pham Minh Quan ◽  
Vu Thi Thu Le ◽  
Tran Quoc Toan ◽  
Do Huu Nghi ◽  
...  
Keyword(s):  
Essential Oils ◽  
Cell Lines ◽  
Antitumor Agents ◽  
Human Tumor ◽  
Cytotoxic Activities ◽  
Human Tumor Cell Lines ◽  
Flame Ionization ◽  
Germacrene D ◽  
Zanthoxylum Nitidum

Zanthoxylum nitidum (Roxb.) DC is a traditional Vietnamese medicine to treat coughs, stomachache, toothache, blood stagnation, and sore throats. The essential oils (EOs) of the leaves, fruits, and stems of this plant were extracted by hydrodistillation and subjected to analysis by gas chromatography (GC)-flame ionization detector (FID) and GC-mass spectrometry (MS). The isolated EOs were then evaluated in terms of their antimicrobial activity by minimum inhibitory concentration (MIC) assay and in vitro cytotoxic effect against 5 human tumor cell lines. GC-MS-FID analysis showed 35, 32, and 25 compounds accounting for 97.6%, 91.7%, and 96.2% of the total EO contents from the leaves, fruits, and stems, respectively. The major compounds of the leaf EO were limonene (44.3%), β-caryophyllene (12.5%), linalool (11.0%), germacrene D (5.3%), and α-pinene (4.9%); the major compounds of the fruit EO were n-pentadecane (34.8%), sabinene (18.3%), and n-heptadecane (4.7%), and the major components of the stem EO were 2-undecanone (72.3%), β-caryophyllene (5.8%), and germacrene D (4.0%). The EOs of leaves, fruits, and stems of Z. nitidum exhibited antibacterial activity against Bacillus subtilis, Escherichia coli, and Fusarium oxysporum with MIC values of 100 µg/mL. The leaf and branch EOs exhibited cytotoxic activity against all tested cancer cell lines, especially A-549 and HepG-2. Findings from the present study provide important knowledge about the potential uses of Z. nitidum EOs as a natural antibacterial and antitumor agents.

Synthesis and Antitumor Evaluation of Novel N-substituted Norcantharidin Imidazolium Derivatives

2018 ◽  
Vol 15 (2) ◽  
pp. 237-245 ◽  
Author(s):  
Rong-Rong Sun ◽  
Jia-Hui Guo ◽  
Cui Yang ◽  
Li-Juan Yang ◽  
Chao Huang
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Antitumor Agents ◽  
Human Tumor ◽  
Imidazole Ring ◽  
Electronic Effects ◽  
Imidazolium Salt ◽  
Ic50 Values ◽  
Human Lung Carcinoma

Aims and Objectives: Cantharidin is a terpenoid with a high vesicant potency isolated from Mylabris caraganae and various other insects, which originates from the Chinese traditional medicine and has a long history of use as antiproliferative agent. Modified cantharidin derivatives are researched for retainable antitumor activities and lower toxicity. And imidazolium salt is an important building block in drug discovery with pharmacological activities. This study was undertaken to identify that N-substituted norcantharidin imidazolium derivatives possess potential bioactivity. Materials and Method: Using readily available furan, maleic anhydride and imidazoles as starting materials, a series of novel N-substituted norcantharidin imidazolium derivatives have been designed and synthesized. The cytotoxic potential of all newly synthesized N-substituted norcantharidin imidazolium derivatives was assessed in vitro against a panel of human tumor cell lines, Human epidermal carcinoma, human lung carcinoma, liver hepatocellular carcinoma, pheochromocytoma of the rat adrenal medulla. Results: The imidazolium derivatives 6a-6f and 6m-6o, bearing a 5,6-dibromohexahydro-4,7-epoxyisobenzofuran- 1,3-dione or 5-bromo-7-oxabicyclo[2.2.1]hepta- 2,5-diene-2,3-dicarboxylate and electron-donating group, carbonyl and propenyl substituent at position-1 of the imidazole ring, were found to be the most potent compounds as antitumor agents. Notably, compounds 6m and 6n exhibited cytotoxic activity selectively against Hela and A549 cell lines with IC50 values 1.38-fold, 5.04-fold, lower than DDP, while compound 6f showed powerful inhibitory activities selectively against Hela and PC12 cell lines. Conclusion: Steric and electronic effects have an important role in determining the cytotoxic activity of imidazolium salts. The norcantharidin-imidazole 6f, 6m, 6n and 6o can be considered to be promising leads for further structural modifications guided by the valuable information derivable.

Novel Thiazine Substituted 9-Anilinoacridines: Synthesis, Antitumour Activity and Structure Activity Relationships

2019 ◽  
Vol 19 (11) ◽  
pp. 1350-1358 ◽  
Author(s):  
R. Kalirajan ◽  
K. Gaurav ◽  
A. Pandiselvi ◽  
B. Gowramma ◽  
S. Sankar
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Antitumor Agents ◽  
Antitumour Activity ◽  
Human Tumor ◽  
Cytotoxic Activities ◽  
Anti Tumour Activity ◽  
Tumour Activity

Background: 9-anilinoacridines are acting as DNA-intercalating agents which plays an important role as antitumor drugs, due to their anti-proliferative properties. Some anticancer agents contain 9- anilinoacridines such as amsacrine (m-AMSA), and nitracrine (Ledakrine) have been already developed. Methods: In this study, novel 9-anilinoacridines substituted with thiazines 4a-r were designed, synthesized, characterized by physical and spectral data and their cytotoxic activities against DLA cell lines were evaluated. Results: Among those compounds, 4b, c, e, g, i, j, k, m, o, p, q, r exhibited significant short term in vitro cytotoxic activity against Daltons lymphoma ascites (DLA) cells with CTC50 value of 0.18 to 0.31μM. The compounds 4b, c, e, g, i, j, k, m, o, p, q, r are also exhibited significant long term in vitro anti-tumour activity against human tumor cell lines, HEp-2 (laryngeal epithelial carcinoma) by Sulforhodamine B assay with CTC50 value of 0.20 to 0.39μM. The compounds 4b, i, j exhibited significant in vivo antitumor activity with % Increase in Life Span (ILS) 48-82%. Conclusion: Results obtained in this study clearly demonstrated that many of the thiazine substituted 9- anilinoacridines exert interesting anti-tumour activity. The compounds 4b, i, j have significant anti-tumour activity and useful drugs after further refinement. The above derivatives will encourage to design future antitumor agents with high therapeutic potentials.

Cytotoxicity and Molecular Targeting Study of Novel 2-Chloro-3- substituted Quinoline Derivatives as Antitumor Agents

2019 ◽  
Vol 16 (3) ◽  
pp. 273-283 ◽  
Author(s):  
Mohammed A.M. Massoud ◽  
Magda A. El-Sayed ◽  
Waleed A. Bayoumi ◽  
Basem Mansour
Keyword(s):  
Cell Lines ◽  
Antitumor Agents ◽  
Growth Factor Receptor ◽  
Human Tumor ◽  
Quinoline Derivatives ◽  
Human Tumor Cell Lines ◽  
Topoisomerase 1 ◽  
Analysis Of Results ◽  
Epidermal Growth

Background: Quinoline scaffold acts as “privileged structure” for anticancer drug design. Certain derivatives showed good results through different mechanisms as topoisomerase 1 and kinase inhibition. </P><P> Methods: A new series of 2-chloro-3-(2-amino-3-cyano-4H-chromene, 4H-pyranyl and fused 1- cyclohexen-4-yl)quinoline structures (3-5, 6 and 7) were designed, synthesized, and evaluated for their in vitro antitumor activity. All compounds were tested by MTT assay against a panel of four different human tumor cell lines. The inhibitory activity of selected compounds was assessed on topoisomerase 1 and epidermal growth factor receptor tyrosine kinase via ELISA. In addition, compounds 7b and 3a were docked into the X-ray crystal structure of Topo 1 and EGFR enzymes, respectively to explain the molecular basis of the potent activity. </P><P> Results: Compounds 3a, 3b and 7b showed characteristic efficacy profile. 7b showed the best cytotoxic activity on all types of tested cell lines with IC50 range (15.8&#177;1.30 to 28.2&#177;3.37 &#181;M), relative to 5-fluoruracil of IC50 range (40.7&#177;2.46 to 63.8&#177;2.69 &#181;M). Via ELISA, 7b and 3a showed characteristic inhibition profile on Topo 1 and EGFR-TK respectively. In addition, 7b has scored binding energy (101.61 kcal/mol) and six hydrogen bonds with amino acids conserved residues in the enzyme pocket. </P><P> Conclusion: Analysis of results revealed that compounds 7a and 7b mainly were Topo 1 inhibitors while 3a was mainly EGFR inhibitor. This property may be exploited to design future quinoline derivatives as antitumor agents with enhanced selectivity towards either of the two molecular targets.

Design and Synthesis of 4(1H)-quinolone Derivatives as Autophagy Inducing Agents by Targeting ATG5 Protein

2020 ◽  
Vol 17 (7) ◽  
pp. 884-890
Author(s):  
Yifan Jia ◽  
Difei Yu ◽  
Qiuhua Huang ◽  
Xiaodong Zhang ◽  
Liqin Qiu ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Antitumor Agents ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Design And Synthesis ◽  
Antiproliferative Agent ◽  
Quinolone Derivatives

Background: Quinolines have been characterized as a class of potential antitumor agents, and a large number of natural and synthetic quinolines acting as antitumor agents were reported. Methods: A series of 7-chloro-4(1H)-quinolone derivatives were synthesized. The antiproliferative effect of these compounds was evaluated by MTT assay against five human tumor cell lines. The mechanism of action of the selected compound 7h was also investigated. Results and Discussion: Most of the compounds had more potent antiproliferative activities than the lead compound 7-chloro-4(1H)-quinolone 6b. Compound 7h was found to be the most potent antiproliferative agent against human tumor cell lines. Further investigation demonstrated that compound 7h triggered ATG5-dependent autophagy of colorectal cancer cells by promoting the functions of LC3 proteins. Conclusion: These results were useful for designing and discovering more potent novel antitumor agents endowed with better pharmacological profiles.

Synthesis and Cytotoxicity of New Mannich Bases of 6-[3-(3,4,5-Trimetoxyphenyl)-2- propenoyl]-2(3H)-Benzoxazolone

2020 ◽  
Vol 17 (4) ◽  
pp. 512-517
Author(s):  
Ognyan Ivanov Petrov ◽  
Yordanka Borisova Ivanova ◽  
Mariana Stefanova Gerova ◽  
Georgi Tsvetanov Momekov
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Biological Activities ◽  
Human Tumor ◽  
Mannich Bases ◽  
In Vitro Cytotoxicity ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

Background: Chemotherapy is one of the mainstays of cancer treatment, despite the serious side effects of the clinically available anticancer drugs. In recent years increasing attention has been directed towards novel agents with improved efficacy and selectivity. Compounds with chalcone backbone have been reported to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, etc. It was reported that aminomethylation of hydroxy chalcones to the corresponding Mannich bases increased their cytotoxicity. In this context, our interest has been focused on the design and synthesis of the so-called multi-target molecules, containing two or more pharmacophore fragments. Methods: A series of Mannich bases were synthesized by the reaction between 6-[3-(3,4,5- trimethoxyphenyl)-2-propenoyl]-2(3Н)-benzoxazolone, formaldehyde, and a secondary amine. The structures of the compounds were confirmed by elemental analysis, IR and NMR spectra. The new Mannich bases were evaluated for their in vitro cytotoxicity against a panel of human tumor cell lines, including BV-173, SKW-3, K-562, HL-60, HD-MY-Z and MDA-MB-231. The effects of selected compounds on the cellular levels of glutathione (GSH) were determined. Results: The new compounds 4a-e exhibited concentration-dependent cytotoxic effects at micromolar concentrations in MTT-dye reduction assay against a panel of human tumor cell lines, similar to those of starting chalcone 3. The tested agents led to concentration - dependent depletion of cellular GSH levels, whereby the effects of the chalcone prototype 3 and its Mannich base-derivatives were comparable. Conclusion: The highest chemosensitivity to the tested compounds was observed in BV- 173followed by SKW-3 and HL-60 cell lines.

Influence of New Synthetic Xanthones on the Proliferation and Migration Potential of Cancer Cell Lines In Vitro

2020 ◽  
Vol 19 (16) ◽  
pp. 1949-1965 ◽  
Author(s):  
Natalia Szkaradek ◽  
Daniel Sypniewski ◽  
Dorota Żelaszczyk ◽  
Sabina Gałka ◽  
Paulina Borzdziłowska ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Higher Plants ◽  
Biological Activities ◽  
Human Tumor ◽  
Plant Metabolites ◽  
Xtt Assay ◽  
Treatment Protocols

Background: Natural plant metabolites and their semisynthetic derivatives have been used for years in cancer therapy. Xanthones are oxygenated heterocyclic compounds produced as secondary metabolites by higher plants, fungi or lichens. Xanthone core may serve as a template in the synthesis of many derivatives that have broad biological activities. Objective: This study synthesized a series of 17 new xanthones, and their anticancer potential was also evaluated. Methods: The anticancer potential was evaluated in vitro using a highly invasive T24 cancer cell line. Direct cytotoxic effects of the xanthones were established by IC50 estimation based on XTT assay. Results: 5 compounds of the total 17 showed significant cytotoxicity toward the studied cancer cultures and were submitted to further detailed analysis, including studies examining their influence on gelatinase A and B expression, as well as on the cancer cells migration and adhesion to an extracellular matrix. These analyses were carried out on five human tumor cell lines: A2780 (ovarian cancer), A549 (lung cancer), HeLa (cervical cancer), Hep G2 (liver cancer), and T24 (urinary bladder cancer). All the compounds, especially 4, showed promising anticancer activity: they exhibited significant cytotoxicity towards all the evaluated cell lines, including MCF-7 breast cancer, and hindered migration-motility activity of cancer cells demonstrating more potent activity than α-mangostin which served as a reference xanthone. Conclusion: These results suggest that our xanthone derivatives may be further analyzed in order to include them in cancer treatment protocols.

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