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.

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.

Design, Synthesis and Biological Evaluation of 3-(3,4,5-Trimethoxyphenyl)- 5-(2-(5-arylbenzo[b]thiophen-3-yl)oxazol-5-yl)isoxazole Derivatives as Anticancer Agents

2020 ◽  
Vol 17 (5) ◽  
pp. 345-351
Author(s):  
Syndla Premalatha ◽  
G. Rambabu ◽  
Islavathu Hatti ◽  
Dittakavi Ramachandran
Keyword(s):  
Breast Cancer ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Isoxazole Derivatives

A new series of 3-(3,4,5-trimethoxyphenyl)-5-(2-(5-arylbenzo[b]thiophen-3-yl)oxa zol-5- yl)isoxazole derivatives were designed and synthesized. All these derivatives were evaluated for their anticancer activity against various human cancer cell lines such as MCF-7 (breast cancer), A549 (lung cancer), DU-145 (prostate cancer) and MDA MB-231 (breast cancer)-four human cancer cell lines by using MTT assay. Here, etoposide was used as a standard reference drug and most of the compounds were exhibited good anticancer activity with respect to cell lines. Among all compounds, five compounds 11b, 11c, 11f, 11i and 11j showed more potent activity than standard drug, in which, compound 11f was the most promising compound.

Novel 1,2,3-Triazole-functionalized pyrido[3',2':4,5]furo[3,2-d]pyrimidin- 4(3H)-one Derivatives: Synthesis, Anticancer Activity, CoMFA and CoMSIA Studies

2020 ◽  
Vol 17 (12) ◽  
pp. 969-978
Author(s):  
Balakishan Vadla ◽  
Sailu Betala
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Normal Cell ◽  
Rational Design ◽  
Human Cancer ◽  
Strong Basis ◽  
Hek 293 ◽  
Normal Cell Line ◽  
Human Cancer Cell Lines ◽  
Mcf 7

A series of novel triazole functionalized pyrido [3',2':4,5] furo[3,2-d] pyrimidin-4 (3H)-one derivatives 7a-p were prepared from ethyl furo[2,3-b]pyridine-2-carboxylate 3 on reaction with ammonia to afford furo[2,3-b]pyridine-2-carboxamide 4. This compound, on reaction with triethyl orthoformate TEOF, gave compound 5. Compound 5 on propargylation, followed by a reaction with substituted aryl azides under Sharpless reaction conditions, furnished triazole tagged pyrido [3',2':4,5]furo[3,2-d] pyrimidin-4(3H)-one derivatives. All the products 7a-p were screened against four human cancer cell lines, such as HeLa - Cervical cancer (CCL-2), COLO 205- Colon cancer (CCL-222), HepG2- Liver cancer (HB-8065), and MCF7 - Breast cancer (HTB-22) and one normal cell line (HEK 293). Compounds 7b, 7n, 7o and 7p, which showed promising anticancer activity, were identified and found to be non-toxic to normal cell line. Studies for HeLa, COLO205, HepG2, and MCF-7 using CoMFA and CoMSIA were carried out . Models from 3D-QSAR provided a strong basis for future rational design of more active and selective HeLa, COLO205, HepG2, and MCF-7 cell line inhibitors.

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 Bimodular Antiparallel G-Quadruplex Nanoconstruct with Antiproliferative Activity

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3625 ◽  
Author(s):  
Antipova ◽  
Samoylenkova ◽  
Savchenko ◽  
Zavyalova ◽  
Revishchin ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Lung Cancer Cell Line ◽  
Ki 67 ◽  
Human Cancer Cell Lines ◽  
G Quadruplex

Oligonucleotides with an antiproliferative activity for human cancer cells have attracted attention over the past decades; many of them have a G-quadruplex structure (GQ), and a cryptic target. In particular, DNA oligonucleotide HD1, a minimal GQ, could inhibit proliferation of some cancer cell lines. The HD1 is a 15-nucleotide DNA oligonucleotide that folds into a minimal chair-like monomolecular antiparallel GQ structure. In this study, for eight human cancer cell lines, we have analyzed the antiproliferative activities of minimal bimodular DNA oligonucleotide, biHD1, which has two HD1 modules covalently linked via single T-nucleotide residue. Oligonucleotide biHD1 exhibits a dose-dependent antiproliferative activity for lung cancer cell line RL-67 and cell line of central nervous system cancer U87 by MTT-test and Ki-67 immunoassay. The study of derivatives of biHD1 for the RL-67 and U87 cell lines revealed a structure-activity correlation of GQ folding and antiproliferative activity. Therefore, a covalent joining of two putative GQ modules within biHD1 molecule provides the antiproliferative activity of initial HD1, opening a possibility to design further GQ multimodular nanoconstructs with antiproliferative activity—either as themselves or as carriers.

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