Four New Xanthones from Cratoxylum cochinchinense and Their In Vitro Antiproliferative Effects

Planta Medica ◽  
2017 ◽  
Vol 83 (09) ◽  
pp. 812-818 ◽  
Author(s):  
Chihiro Ito ◽  
Takuya Matsui ◽  
Ai Niimi ◽  
Hugh Tan ◽  
Masataka Itoigawa
Keyword(s):  
Mitochondrial Membrane ◽  
Chemical Constituents ◽  
Lymphoblastic Leukemia ◽  
A549 Cells ◽  
Kb Cells ◽  
Human Carcinoma ◽  
Antiproliferative Effects ◽  
Ic50 Values ◽  
Lung Adenocarcinoma A549

AbstractThe study of the chemical constituents of branches and twigs of Cratoxylum cochinchinense collected in Singapore led to the isolation and structural elucidation of four new xanthones, named cratoxanthone A (1), B (2), C (3), and D (4), together with six known xanthones (5–10) and one known dihydroanthracenone (11). Eight xanthones (including 1 and 2) and 11 were tested for their antiproliferative activity in three human carcinoma cell lines (lung adenocarcinoma A549, colorectal carcinoma Colo205, and epidermoid carcinoma KB) and a human acute lymphoblastic leukemia B cell line (NALM-6), and the mitochondrial membrane potential was determined in KB cells. New xanthones 1 and 2 attenuated NALM-6 cell proliferation with IC50 values of 17.78 and 8.27 µM, respectively. Furthermore, KB cells treated with these compounds had significantly decreased mitochondrial membrane potentials. Notably, the proliferation of A549 cells was specifically inhibited by 11, but not the xanthones.

scholarly journals Chemical Constituents of the Deep-Sea-Derived Penicillium solitum

Marine Drugs ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. 580
Author(s):  
Zhi-Hui He ◽  
Jia Wu ◽  
Lin Xu ◽  
Man-Yi Hu ◽  
Ming-Ming Xie ◽  
...  
Keyword(s):  
Deep Sea ◽  
Chemical Constituents ◽  
A549 Cells ◽  
Acid Methyl Ester ◽  
2D Nmr ◽  
Positive Control ◽  
Ic50 Values ◽  
Penicillium Solitum ◽  
New Compounds

A systematic chemical investigation of the deep-sea-derived fungus Penicillium solitum MCCC 3A00215 resulted in the isolation of one novel polyketide (1), two new alkaloids (2 and 3), and 22 known (4–25) compounds. The structures of the new compounds were established mainly on the basis of exhaustive analysis of 1D and 2D NMR data. Viridicatol (13) displayed moderate anti-tumor activities against PANC-1, Hela, and A549 cells with IC50 values of around 20 μM. Moreover, 13 displayed potent in vitro anti-food allergic activity with an IC50 value of 13 μM, compared to that of 92 μM for the positive control, loratadine, while indole-3-acetic acid methyl ester (9) and penicopeptide A (10) showed moderate effects (IC50 = 50 and 58 μM, respectively).

Geraniin induces apoptotic cell death in human lung adenocarcinoma A549 cells in vitro and in vivo

2013 ◽  
Vol 91 (12) ◽  
pp. 1016-1024 ◽  
Author(s):  
Jia Li ◽  
Siran Wang ◽  
Jimei Yin ◽  
Linna Pan
Keyword(s):  
Cytochrome C ◽  
Mitochondrial Membrane ◽  
Apoptotic Cell ◽  
A549 Cells ◽  
Tumor Growth Inhibition ◽  
Dependent Manner ◽  
Cytochrome C Release ◽  
Lung Adenocarcinoma A549

Geraniin has previously been reported to possess extensive biological activity. In this study, we reported that geraniin is an inhibitor of tumor activity in vitro and in vivo. Geraniin suppressed the proliferation of A549 cells in a dose- and time-dependent manner. Geraniin arrested the cell cycle in the S phase and induced a significant accumulation of reactive oxygen species (ROS), as well as an increased percentage of cells with mitochondrial membrane potential (MMP) disruption. Western blot analysis showed that geraniin inhibited Bcl-2 expression and induced Bax expression to disintegrate the outer mitochondrial membrane and cause cytochrome c release. Mitochondrial cytochrome c release was associated with the activation of caspase-9 and caspase-3 cascades. Additionally, geraniin resulted in tumor growth inhibition in A549 xenografts. Our results indicate cytotoxic activity of geraniin towards cancer cells in vitro and in vivo.

Synthesis and Antitumor Activity Evaluation of New Phenanthrene-Based Tylophorine Derivatives

2019 ◽  
Vol 16 (6) ◽  
pp. 462-467
Author(s):  
Songtao Li ◽  
Hongling Zhao ◽  
Zhifeng Yin ◽  
Shuhua Deng ◽  
Yang Gao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Antitumor Activities ◽  
Human Carcinoma ◽  
Carcinoma Cell Lines ◽  
Structure Activity ◽  
Human Carcinoma Cell ◽  
Ic50 Values ◽  
Relationship Of

A series of new phenanthrene-based tylophorine derivatives (PBTs) were synthesized in good yield and their structures were characterized by 1H-NMR spectroscopy and ESI MS. In vitro antitumor activity of these compounds against five human carcinoma cell lines, including HCT116 (colorectal), BGC-823 (gastric), HepG-2 (hepatic), Hela (cervical) and H460 (lung) cells, was evaluated by MTT assay. Among these PBTs, compound 6b showed the highest antitumor activities against HCT116 and HepG-2 cell lines with IC50 values of 6.1 and 6.4 μM, respectively, which were comparable to that of adriamycin hydrochloride. The structure-activity relationship of these compounds was also discussed based on the results of their antitumor activity.

Synthesis and Anti-Tumor Activity Evaluation of Novel 7-Fluoro-4-(1- Piperazinyl) Quinolines

2019 ◽  
Vol 16 (6) ◽  
pp. 663-669
Author(s):  
Dan Liu ◽  
Aiqi Xue ◽  
Zhixin Liu ◽  
Yi Zhang ◽  
Penghui Peng ◽  
...  
Keyword(s):  
Spectral Analysis ◽  
Cancer Therapy ◽  
Carcinoma Cell ◽  
A549 Cells ◽  
Quinoline Derivatives ◽  
Human Carcinoma ◽  
Carcinoma Cell Lines ◽  
Human Carcinoma Cell ◽  
Anti Tumor Activity

Background: Three series of new 7-fluoro-4-(1-piperazinyl) quinolines (I1~I6, II1~II2 and IV1~IV4) were synthesized. Their anti-tumor activity was evaluated in vitro against three human carcinoma cell lines, namely SGC-7901 cells, BEL-7402 cells and A549 cells expressing high levels of EGFR by Methyl Thiazolyl Terazolium (MTT) assay. Methods: Three series of quinoline derivatives were synthesized, characterized and evaluated for their in vitro anti-tumor activities. Results and Discussion: Structures of the newly synthesized compounds were confirmed by spectral analysis. The preliminary bioassay indicated that compounds I1, I10 and II1 exhibited better anti-tumor activity than the rest of the target compounds and gefitinib against A549 cell based assay, which demonstrated that compounds I1, I10 and II1 are potential agents for cancer therapy. Results suggested that the substitutes on piperazinyl influenced anti-tumor activities remarkably. Conclusion: These results are useful for discovering more potent novel anti-tumor compounds and further studies are ongoing.

scholarly journals Evaluation of anticancer activity in vitro of a stable copper(I) complex with phosphine-peptide conjugate

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Urszula K. Komarnicka ◽  
Barbara Pucelik ◽  
Daria Wojtala ◽  
Monika K. Lesiów ◽  
Grażyna Stochel ◽  
...  
Keyword(s):  
A549 Cells ◽  
Ros Generation ◽  
Dependent Manner ◽  
Hacat Cells ◽  
Icp Ms ◽  
Intracellular Ros ◽  
M Phase ◽  
Lung Adenocarcinoma A549 ◽  
Induced Apoptosis

Abstract[CuI(2,9-dimethyl-1,10-phenanthroline)P(p-OCH3-Ph)2CH2SarcosineGlycine] (1-MPSG), highly stable in physiological media phosphino copper(I) complex—is proposed herein as a viable alternative to anticancer platinum-based drugs. It is noteworthy that, 1-MPSG significantly and selectively reduced cell viability in a 3D spheroidal model of human lung adenocarcinoma (A549), in comparison with non-cancerous HaCaT cells. Confocal microscopy and an ICP-MS analysis showed that 1-MPSG effectively accumulates inside A549 cells with colocalization in mitochondria and nuclei. A precise cytometric analysis revealed a predominance of apoptosis over the other types of cell death. In the case of HaCaT cells, the overall cytotoxicity was significantly lower, indicating the selective activity of 1-MPSG towards cancer cells. Apoptosis also manifested itself in a decrease in mitochondrial membrane potential along with the activation of caspases-3/9. Moreover, the caspase inhibitor (Z-VAD-FMK) pretreatment led to decreased level of apoptosis (more pronouncedly in A549 cells than in non-cancerous HaCaT cells) and further validated the caspases dependence in 1-MPSG-induced apoptosis. Furthermore, the 1-MPSG complex presumably induces the changes in the cell cycle leading to G2/M phase arrest in a dose-dependent manner. It was also observed that the 1-MPSG mediated intracellular ROS alterations in A549 and HaCaT cells. These results, proved by fluorescence spectroscopy, and flow cytometry, suggest that investigated Cu(I) compound may trigger apoptosis also through ROS generation.

scholarly journals Structurally Simple Phenanthridine Analogues Based on Nitidine and Their Antitumor Activities

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 437
Author(s):  
Shu-Qin Qin ◽  
Lian-Chun Li ◽  
Jing-Ru Song ◽  
Hai-Yun Li ◽  
Dian-Peng Li
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
A549 Cells ◽  
Anticancer Activities ◽  
Human Cancer Cell Lines ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Diphenyl Tetrazolium Bromide ◽  
Conjugated Compounds

A series of novel structurally simple analogues based on nitidine was designed and synthesized in search of potent anticancer agents. The antitumor activity against human cancer cell lines (HepG2, A549, NCI-H460, and CNE1) was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The results showed that some of them had good anticancer activities, especially derivatives with a [(dimethylamino)ethyl]amino side chain in the C-6 position. Planar conjugated compounds 15a, 15b, and 15c, with IC50 values of 1.20 μM, 1.87 μM, and 1.19 μM against CNE1 cells, respectively, were more active than nitidine chloride. Compound 15b and compound 15c with IC50 values of 1.19 μM and 1.37 μM against HepG2 cells and A549 cells demonstrated superior activities to nitidine. Besides, compound 5e which had a phenanthridinone core displayed extraordinary cytotoxicity against all test cells, particularly against CNE1 cells with the IC50 value of 1.13 μM.

scholarly journals Protoflavone-Chalcone Hybrids Exhibit Enhanced Antitumor Action through Modulating Redox Balance, Depolarizing the Mitochondrial Membrane, and Inhibiting ATR-Dependent Signaling

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 519 ◽  
Author(s):  
Ahmed Dhahir Latif ◽  
Tamás Jernei ◽  
Ana Podolski-Renić ◽  
Ching-Ying Kuo ◽  
Máté Vágvölgyi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mitochondrial Membrane ◽  
Redox Balance ◽  
Breast Cancer Cell Lines ◽  
Antitumor Action ◽  
Hybrid Compounds ◽  
Mitochondrial Membrane Depolarization ◽  
Ic50 Values ◽  
Novel Strategy

Hybrid compounds combine fragments with complementary targets to achieve a common pharmacological goal. This approach represents an increasingly popular strategy for drug discovery. In this work, we aimed to design antitumor hybrid compounds based on an inhibitor of ataxia-telangiectasia and Rad3-related protein (ATR)-dependent signaling, protoapigenone, and a pro-oxidant ferrocene or chalcone fragment. Four new triazole-coupled hybrids were prepared. The compounds were cytotoxic against human breast cancer cell lines in vitro, showing IC50 values in the sub-micromolar range. The nature of interactions between relevant fragments of the hybrids was evaluated by the Chou–Talalay method. Experimental combination treatment with the fragments showed additive effects or slight/moderate synergism, while strong synergism was observed when the fragments were virtually combined into their hybrids, suggesting a relevant pharmacological benefit of the coupling. All hybrids were strong inhibitors of the ATR-mediated activation of Chk1, and they interfered with the redox balance of the cells leading to mitochondrial membrane depolarization. Additionally, they induced late apoptosis and primary necrosis in MDA-MB-231 and MCF-7 breast cancer cells, respectively. Our results demonstrate that coupling the ATR-dependent signaling inhibitor protoflavone with a pro-oxidant chalcone dramatically increases the antitumor activity compared with either fragment alone. Such compounds may offer an attractive novel strategy for the treatment of various cancers.

scholarly journals Microwave-Assisted Synthesis, Proton Dissociation Processes, and Anticancer Evaluation of Novel D-Ring-Fused Steroidal 5-Amino-1-Arylpyrazoles

2019 ◽  
Vol 10 (1) ◽  
pp. 229
Author(s):  
Gergő Mótyán ◽  
Ádám Baji ◽  
Małgorzata Anna Marć ◽  
Mohana Krishna Gopisetty ◽  
Dóra I. Adamecz ◽  
...  
Keyword(s):  
Human Cancer ◽  
Condensation Reaction ◽  
Microwave Assisted Synthesis ◽  
Antiproliferative Effects ◽  
Human Cancer Cells ◽  
Microwave Assisted ◽  
Proton Dissociation ◽  
Ic50 Values ◽  
Spectrophotometric Titrations

Taking into account the pharmacological relevance of heterocycle-fused natural steroids, the objective of the current study was to develop a multistep reaction sequence for the efficient synthesis of novel D-ring-condensed 5-amino-1-arylpyrazoles from dehydroepiandrosterone (DHEA). A condensation reaction of 16-formyl-DHEA with hydroxylamine afforded the corresponding oxime, which was demonstrated to be stable in one of its cyclic isoxazoline forms due to possible ring-chain tautomerism. The subsequent base-induced dehydration to a diastereomeric β-ketonitrile, followed by microwave-assisted heterocyclization with different arylhydrazines led to the desired pyrazoles. The generally good yields of the products depended slightly on the electronic character of the substituent present on the aromatic ring of the reagent. The proton dissociation processes of the DHEA-derived heterocycles were investigated in aqueous solution by UV-visible spectrophotometric titrations to reveal their actual chemical forms at physiological pH. The determined pKa values attributed to the pyrazole NH+ moiety were low (1.8–4.0) and varied by the different substituents of the benzene ring. The antiproliferative effects of the structurally similar compounds were screened in vitro on human cancer cells (namely on HeLa, U2Os, MCF-7, PC-3, and A549), along with a noncancerous cell line (MRC-5). The IC50 values of the most active derivative were determined on all cell lines.

scholarly journals Chemical Constituents of Stems and Leaves of Tagetespatula L. and Its Fingerprint

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3911 ◽  
Author(s):  
Yu-Meng Wang ◽  
Xiao-Ku Ran ◽  
Muhammad Riaz ◽  
Miao Yu ◽  
Qian Cai ◽  
...  
Keyword(s):  
High Performance ◽  
High Resolution Mass Spectrometry ◽  
Chemical Constituents ◽  
Human Gastric Cancer ◽  
Chemical Structures ◽  
Yellow Color ◽  
Ic50 Values ◽  
Gastric Cancer Cell Lines ◽  
Stems And Leaves

Tagetespatula L. is a widely cultivated herbal medicinal plant in China and other countries. In this study, two new 2, 3-dihydrobenzofuran glucosides (1, 2) and fourteen known metabolites (3–16) were isolated from the stems and leaves of T. patula (SLT). The chemical structures of the isolated compounds were characterized comprehensively based on one- and two-dimensional NMR spectroscopy and high resolution mass spectrometry. Absolute configurations of compounds 1 and 2 were determined by ECD calculations. Compounds 1 and 2 exhibited moderate in vitro inhibitory activities against human gastric cancer cell lines (AGS) with IC50 values of 41.20 μmol/L and 30.43 μmol/L, respectively. The fingerprint profiles of stems and leaves of T. patula with three color types of flowers (Janie Yellow Bright, Jinmen Orange, Shouyao Red and Yellow color) were established by high-performance liquid chromatography (HPLC). Ten different batches of stems and leaves were examined as follow: Shouyao Red and Yellow color (1, 2, 3), Janie Yellow Bright (4, 5, 6, 7) and Jinmen Orange (8, 9, 10). Twenty-two common peaks were identified with similarity values ranging from 0.910 to 0.977. Meanwhile, the average peak area of SLT in the three types of flowers was different and it was the highest in Janie Yellow Bright.

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