scholarly journals BF3-OEt2 Catalyzed C3-Alkylation of Indole: Synthesis of Indolylsuccinimidesand Their Cytotoxicity Studies

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2202
Author(s):  
Iqbal N. Shaikh ◽  
Abdul Rahim ◽  
Shaikh Faazil ◽  
Syed Farooq Adil ◽  
Mohamed E. Assal ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cancer ◽  
A549 Cells ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines ◽  
Cytotoxicity Studies ◽  
Ic50 Value ◽  
Hepg2 Cell Lines ◽  
Ht 29

A simple and efficient BF3-OEt2 promoted C3-alkylation of indole has been developed to obtain3-indolylsuccinimidesfrom commercially available indoles and maleimides, with excellent yields under mild reaction conditions. Furthermore, anti-proliferative activity of these conjugates was evaluated against HT-29 (Colorectal), Hepg2 (Liver) and A549 (Lung) human cancer cell lines. One of the compounds, 3w, having N,N-Dimethylatedindolylsuccinimide is a potent congener amongst the series with IC50 value 0.02 µM and 0.8 µM against HT-29 and Hepg2 cell lines, respectively, and compound 3i was most active amongst the series with IC50 value 1.5 µM against A549 cells. Molecular docking study and mechanism of reaction have briefly beendiscussed. This method is better than previous reports in view of yield and substrate scope including electron deficient indoles.

scholarly journals Synthesis and Anticancer Activity Evaluation of Azepinobisindoles; the Isomeric Iheyamine A Derivatives

2019 ◽  
Vol 35 (2) ◽  
pp. 723-731
Author(s):  
Weerachai Phutdhawong ◽  
Sopita Rattanopas ◽  
Jitnapa Sirirak ◽  
Thongchai Taechowisan ◽  
Waya S. Phutdhawong
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Human Cancer ◽  
Docking Study ◽  
Inhibitory Effect ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines ◽  
Activity Evaluation ◽  
Cancer Line

Azepinobisindole derivatives, the isomeric Iheyamine skeleton, was prepared and its anticancer activity evaluation were investigated against two human cancer cell lines, Hepatocellular carcinoma (HepG2) and human cervical cancer line (Hela) as well as the normal cell line (Vero cell line) using MTT assay. The anticancer activity results indicated that 2-methoxy-5-methyl-5H-azepino[2,3-b:4,5-bʹ]diindole was the most active derivative against tested cell lines. Additionally, molecular docking study in silico the possible inhibitory effect of cyclin-dependent kinase 2 (CDK2) by the azepinoindole revealed that all synthesized compounds fit well in the binding cavity of CDK2.

scholarly journals Development of Coumarin-Based Hydroxamates as Histone Deacetylase Inhibitors with Antitumor Activities

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 717 ◽  
Author(s):  
Na Zhao ◽  
Feifei Yang ◽  
Lina Han ◽  
Yuhua Qu ◽  
Di Ge ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Histone Deacetylase ◽  
Cell Lines ◽  
Histone Deacetylases ◽  
Histone Deacetylase Inhibitors ◽  
Human Cancer ◽  
Immunoblot Analysis ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines

Histone deacetylases (HDACs) have been proved to be promising targets for the treatment of cancer, and five histone deacetylase inhibitors (HDACis) have been approved on the market for the treatment of different lymphomas. In our previous work, we designed a series of novel coumarin-containing hydroxamate HDACis, among which compounds 6 and 7 displayed promising activities against tumor growth. Based on a molecular docking study, we further developed 26 additional analogues with the aim to improve activity of designed compounds. Several of these new derivatives not only showed excellent HDAC1 inhibitory effects, but also displayed significant growth inhibitory activities against four human cancer cell lines. Representative compounds, 13a and 13c, showed potent anti-proliferative activities against solid tumor cell lines with IC50 values of 0.36–2.91 µM and low cytotoxicity against Beas-2B and L-02 normal cells. Immunoblot analysis revealed that 13a and 13c dose-dependently increased the acetylation of histone H3 and H4. Importantly, the two compounds displayed much better anti-metastatic effects than SAHA against the MDA-MB-231 cell line. Moreover, 13a and 13c arrested MDA-MB-231 cells at G2/M phase and induced MDA-MB-231 cell apoptosis. Finally, the molecular docking study rationalized the high potency of compound 13c.

scholarly journals Design, Synthesis, and Molecular Docking Study of Novel Heterocycles Incorporating 1,3,4-Thiadiazole Moiety as Potential Antimicrobial and Anticancer Agents

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1066 ◽  
Author(s):  
Mohamed El-Naggar ◽  
Hanan A. Sallam ◽  
Safaa S. Shaban ◽  
Salwa S. Abdel-Wahab ◽  
Abd El-Galil E. Amr ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Reference Drug ◽  
Human Cancer Cell Lines ◽  
Dhfr Inhibitors

A new series of 5-(3,5-dinitrophenyl)-1,3,4-thiadiazole derivatives were prepared and evaluated for their in vitro antimicrobial, antitumor, and DHFR inhibition activity. Compounds 9, 10, 13, and 16 showed strong and broad-spectrum antimicrobial activity comparable to Amoxicillin and Fluconazole as positive antibiotic and antifungal controls, respectively. Compounds 6, 14, and 15 exhibited antitumor activity against four human cancer cell lines, CCRF-CEM leukemia, HCT-15 colon, PC-3 prostate, and UACC-257 melanoma cell lines using Doxorubicin as a reference drug. Compounds 10, 13, 14, and 15 proved to be the most active DHFR inhibitors with an IC50 range of 0.04 ± 0.82–1.00 ± 0.85 µM, in comparison with Methotrexate (IC50 = 0.14 ± 1.38 µM). The highly potent DHFR inhibitors shared a similar molecular docking mode and made a critical hydrogen bond and arene‒arene interactions via Ser59 and Phe31 amino acid residues, respectively.

scholarly journals Design, Synthesis, and Anticancer Activities of Novel 2-Amino-4-phenylthiazole Scaffold Containing Amide Moieties

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Zhi-Hua Zhang ◽  
Hong-Mei Wu ◽  
Sai-Nan Deng ◽  
Xiao-Yu Cai ◽  
Yu Yao ◽  
...  
Keyword(s):  
Cell Lines ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Structural Characteristics ◽  
Docking Study ◽  
Anticancer Activities ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines ◽  
Biological Studies

Appropriately substituted 2-amino-4-phenylthiazole derivatives were designed and synthesized according to the structural characteristics of crizotinib. The obtained compounds were characterized using 1H NMR, 13C NMR, and HRMS. The target compounds 5a–o were evaluated for their in vitro antiproliferative activity against A549, HeLa, HT29, and Karpas299 human cancer cell lines. Based on results of biological studies, some of these compounds exhibited significant antiproliferative activity. Compound 5b possessed outstanding growth inhibitory effects on the four cell lines, especially for HT29 cell with IC50 value of 2.01 µM. Along with the biological assay data, a molecular docking study suggests that the target compounds were a potential inhibitor.

Synthesis and Cytotoxicity Assessment of Novel 7-O- and 14-O-Derivatives of Glaucocalyxin A

2020 ◽  
Vol 20 (10) ◽  
pp. 1241-1249
Author(s):  
Hong-Chuan Liu ◽  
Li-Ming Qiao ◽  
Wei Zheng ◽  
Zhao-Bao Xiang ◽  
Hai-Sheng Chen ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Folk Medicine ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Human Cancer Cell Lines ◽  
Derivatives Of

Background: Rabdosia japonica has been historically used in China as a popular folk medicine for the treatment of cancer, hepatitis, and gastricism. Glaucocalyxin A (GLA), an ent-kaurene diterpene isolated from Rabdosia japonica, is one of the main active ingredients showing potent inhibitory effects against several types of tumor cells. To the best of our knowledge, studies regarding the structural modification and Structure- Activity Relations (SAR) of this compound have not yet been reported. Objective: The aim of this study was to discover more potent derivatives of GLA and investigate their SAR and cytotoxicity mechanisms. Methods: Novel 7-O- and 14-O-derivatives of GLA were synthesized by condensation of acids or acyl chloride. The anti-tumor activities of these derivatives against various human cancer cell lines were evaluated in vitro by MTT assays. Apoptosis assays of compound 17 (7,14-diacylation product) were performed on A549 and HL-60 cells by flow cytometry and TUNNEL. The acute toxicity of this compound was tested on mice, at the dose of 300mg per kg body weight. Results: Seventeen novel 7-O- and 14-O-derivatives of GLA (1-17) were synthesized. These compounds showed potent cytotoxicity against the tested cancer cell lines, and almost all of them were found to be more cytotoxic than GLA and oridonin. Of the synthesized derivatives, compound 17 presented the greatest cytotoxicity, with IC50 values of 0.26μM and 1.10μM in HL-60 and CCRF-CEM cells, respectively. Furthermore, this compound induced weak apoptosis of A549 cells but showed great potential in stimulating the apoptosis of HL- 60 cells. Acute toxicity assays indicated that compound 17 is relatively safer. Conclusion: The results reported herein indicate that the synthesized GLA derivatives exhibited greater cytotoxicity against leukemia cells than against other types of tumors. In particular, 7,14-diacylation product of GLA was found to be an effective anti-tumor agent. However, the cytotoxicity mechanism of this product in A549 cells is expected to be different than that in other tumor cell lines. Further research is needed to confirm this hypothesis.

scholarly journals Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3923
Author(s):  
Adel A.-H. Abdel-Rahman ◽  
Amira K. F. Shaban ◽  
Ibrahim F. Nassar ◽  
Dina S. EL-Kady ◽  
Nasser S. M. Ismail ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Molecular Docking Study ◽  
Human Cancer Cell Lines ◽  
Hct 116 ◽  
Mcf 7

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

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 Comparative Antiproliferative activity of aerial parts of few Apocynaceae plants in HepG2, HT29 and SK-OV3 Human cancer cell lines

2019 ◽  
Vol 9 (4-s) ◽  
pp. 1195-1202
Author(s):  
Nirmala Devi ◽  
Ajay Kumar Gupta ◽  
Sunil Kumar Prajapati
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Srb Assay ◽  
Human Cancer Cell Lines ◽  
Aerial Parts ◽  
Carissa Carandas ◽  
Ht 29

Aims: Apocynaceae family is the 5th largest medicinal plant family rich in potent secondary metabolites such as Alkaloids, Cardiac glycosides,Terpenoids, irridoid/secoirridoids, flavonoids and Phenolic contents. The present study was aimed to evaluate and compare in-vitroantiproliferative activity of three plants of this family.Methods: Aerial parts of Carissa carandas Linn. (C), Nerium indicum Mill. (N) and Wrightia tinctoria RBr. (W), were collected and dried. Thepowdered drugs were extracted in Ethanol (1), 60% Ethanol (2) and Water (3). Estimation of Phytoconstituents performed using standardmethods. In-vitro cytotoxic activity performed using Sulphorhodamine B (SRB) assay in HepG2, HT29 and SKOV3 human cancer cell lines takingAdriamycin (ADR) as standard. For extracts, GI50 value ≤ 20μg/ml was considered to demonstrate activity.Results: For HepG2 cell line graphs and photomicrographs showed GI50 value as ADR=39.79, C1=2.5, N2=66.3, N3<10 and C2=C3= N1=W1-3>80. Also TGI for C1>80. The extracts, C1, C2, N1, N2, and N3 were found to possess activity against HepG2.These extracts were screened onHT 29 and SKOV3cell lines. The GI50 value observed was<10 for C1, N2, N3 and ADR in HT 29 and <10 for N3 and ADR in SK OV3 cell lines.Thus it was found that aqueous extract of Nerium indicum (N3) and Ethanolic extract of Carissa carandas (C1) were most cytotoxic extractsagainst all three cell lines.Conclusions: our study establishes that Apocynaceae family plants could be an important anticancer lead and could serve as Botanical drug forneoplasia.Keywords: Apocynaceae, SRB Assay, Phytoconstituents, Anticancer drug screening models, Hep G2, HT 29, SK-OV3, HCC.

scholarly journals Anticancer effect of the fruit and seed extracts of Momordica charantia L. (Cucurbitaceae) on human cancer cell lines

2021 ◽  
Vol 18 (10) ◽  
pp. 2057-2065
Author(s):  
Hatice Güneş ◽  
Mehlika Alper ◽  
Nevin Çelikoğlu
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
A549 Cells ◽  
K562 Cells ◽  
Cancer Cell Lines ◽  
Fruit Extract ◽  
Human Cancer Cell Lines ◽  
Seed Extracts ◽  
Mcf 7

Purpose: To investigate anticancer effects of Momordica charantia L. (M. charantia) fruit and seed extracts on some cancer cell lines. Methods: Human cancer cell lines, including lung cancer (A549), breast cancer (MCF-7), chronic myeloid leukemia (K562) and T cell leukemia (Jurkat) were incubated with the extracts (0 - 0.8 mg/mL) for 72 h. The cytotoxic effects of the extracts were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5- dipenyltetrazolium bromide (MTT) assay. A549 and MCF-7 cells were treated with the ethanol fruit extract (FE) for 24 h and stained with propidium iodide (PI) for the analysis of cell cycle arrest using flow cytometry. Annexin V-FITC/PI staining along with flow cytometry analysis and caspase-3 assays were carried out to determine the apoptosis of the cells treated with FE extract for 24 h. Vascular endothelial growth factor (VEGF) secretion of the cells exposed to FE extract for 1 h was determined using enzyme-linked immunosorbent assay (ELISA). Cell invasion assay was applied to detect cell migration after treatment with FE extract for 48 h. Results: Ethanol fruit extract (FE) resulted in 90, 92, 85 and 87 % cytotoxicity against K562, A549, MCF-7 and Jurkat cell lines, respectively. However, ethanol seed extract of seed (SE) was less effective (≤42 %) on cytotoxicity against cancer cells. Acetone fruit extract (FA) caused 82, 75 and 59 % cytotoxicity on MCF-7, Jurkat and K562 cells, respectively, whereas 20 % cytotoxicity was observed on A549 cells. Dose analyses of FE extract indicated that K562 cells had the lowest IC50 value (0.082 mg/mL). In addition, FE extract treatment caused accumulation of A549 and MCF-7 cells in the S phase of the cell cycle. Moreover, apoptotic cell death was observed in A549 or MCF-7 cells treated with the FE extract. While the treatment of A549 cells with LPS for 24 h resulted in 19-fold increase in VEGF secretion, combination of FE with LPS caused 9.6-fold decrease in VEGF secretion, indicating the antiangiogenic activity of FE extract. Furthermore, FE extract treatment led to a significant decrease in the invasive properties of A549 and PC-3 cells when compared to untreated cells. Conclusion: Among the M. charantia extracts, FE extract displayed the highest anticancer potency against cancer cell lines, indicating that M. charantia FE extract may be a potential source for development of anticancer compounds in future.

scholarly journals A New Bibenzyl-phenanthrene Derivative from Dendrobium signatum and its Cytotoxic Activity

2016 ◽  
Vol 11 (5) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Arparporn Mittraphab ◽  
Chawanphat Muangnoi ◽  
Kittisak Likhitwitayawuid ◽  
Pornchai Rojsitthisak ◽  
Boonchoo Sritularak
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Human Cancer ◽  
Mass Spectrometric ◽  
Human Cancer Cell ◽  
Mass Spectrometric Data ◽  
Human Cancer Cell Lines ◽  
Spectrometric Data ◽  
Whole Plant ◽  
Ht 29

From the whole plant of Dendrobium signatum, a new bibenzyl-dihydrophenanthrene derivative, named dendrosignatol was isolated, together with the known compounds 3,4-dihydroxy-3,4′-dimethoxybibenzyl, dendrocandin B, dendrocandin I and dendrofalconerol A. The structure of the new compound was elucidated through analysis of its spectroscopic and mass spectrometric data. All of the isolates showed appreciable cytotoxic activity against three human cancer cell lines, including MDA-231, HepG2 and HT-29 cells.

Sign in / Sign up

Export Citation Format

Share Document