scholarly journals Synthesis, Anti-proliferative Activity, and Molecular Docking Study of New Series of 1,3-5-Triazine Schiff Base Derivatives

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4065
Author(s):  
Hessa H. Al Rasheed ◽  
Azizah M. Malebari ◽  
Kholood A. Dahlous ◽  
Darren Fayne ◽  
Ayman El-Faham
Keyword(s):  
Schiff Base ◽  
Molecular Docking ◽  
Cell Lines ◽  
Proliferative Activity ◽  
Docking Study ◽  
Reference Compound ◽  
Molecular Docking Study ◽  
Schiff Base Derivatives ◽  
Hct 116 ◽  
Mcf 7

Based on the use of s-triazine as a scaffold, we report here a new series of s-triazine Schiff base derivatives and their anti-proliferative activity against two cancer cell lines: human breast carcinoma (MCF-7), and colon cancer (HCT-116) compared with tamoxifen as a reference compound. Several derivatives exhibited growth inhibition activity in the sub-micromolar range. The results reveal that the s-triazine Schiff base derivatives showed varied activities and that the substituents on the s-triazine core have a great effect on the anti-proliferative activity. Compounds with a piperidino and benzylamino substituent on the s-triazine moiety 4b and 4c were most effective in both cell lines compared to the reference compound used. In addition, compound 4b has a para chlorine atom on the benzylidine residue, demonstrating the most potent activity with IC50 values of 3.29 and 3.64 µM in MCF-7 and HCT-116, respectively. These results indicate that in general, the nature of the substituents on the triazine core and the type of substituent on the benzilyldene ring significantly influenced the anti-proliferative activity. The results obtained from the anti-proliferative activity and the molecular docking study indicate that s-triazine-hydrazone derivatives may be an excellent scaffold for the development of new anti-cancer agents.

scholarly journals Unexpected Synthesis, Single-Crystal X-ray Structure, Anticancer Activity, and Molecular Docking Studies of Certain 2–((Imidazole/Benzimidazol–2–yl)thio)–1–arylethanones

Crystals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 446
Author(s):  
Tarfah Al-Warhi ◽  
Mohamed Said ◽  
Mahmoud El Hassab ◽  
Nada Aljaeed ◽  
Hazem Ghabour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Single Crystal ◽  
Cell Lines ◽  
Docking Study ◽  
Anticancer Activities ◽  
Molecular Docking Study ◽  
X Ray ◽  
Mcf 7

In connection with our research program concerning development of novel effective benzimidazole-based anticancer candidates, herein we describe a new unexpected synthetic route to obtain a series of 2–((imidazole/benzimidazol2–yl)thio)1–arylethanones endowed with promising anti-breast cancer and Cyclin-dependent kinase 2 (CDK2) inhibitory activities. Contrary to expectations, products for the reaction of 2–mercaptoimidazole/benzimidazole 2a,b with β–keto esters 6a–c were unambiguously assigned as 2–((imidazol/benzimidazol2–yl)thio)1–arylethanones 10a–f based on NMR spectroscopy and single-crystal X-ray crystallographic analyses. In vitro anticancer activities for herein reported imidazole/benzimidazoles 10a–f were assessed through a cell-based assay against human breast cancer T4–7D and MCF–7 cell lines. Benzimidazoles 10d–f exerted better anti-proliferative action towards T4–7D and MCF–7 cell lines than their corresponding imidazole counterparts 10a–c. Furthermore, a molecular docking study suggested CDK2 kinase as a potential enzymatic target for benzimidazoles 10d–f, and investigated their possible binding pattern and interactions within CDK2 active site. Thereafter, benzimidazoles 10d–f were in vitro examined for their CDK2 inhibitory action, where they exerted good activity. Finally, several key ADME and druglikeness properties were predicted by the SwissADME online tool. Interestingly, benzimidazoles 10d–f were found to have no violations in all druglikeness rules (Veber, Lipinski, Ghose, Muegge, and Egan). In addition, they had neither PAINS nor structural alerts (Brenks). In conclusion, benzimidazoles 10d–f demonstrated not only a promising anticancer activities but also an acceptable ADME and physicochemical properties especially benzimidazole 10e.

scholarly journals New 1,2,3-Triazole-Containing Hybrids as Antitumor Candidates: Design, Click Reaction Synthesis, DFT Calculations, and Molecular Docking Study

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 708
Author(s):  
Islam H. El Azab ◽  
Hamdy S. El-Sheshtawy ◽  
Rania B. Bakr ◽  
Nadia A. A. Elkanzi
Keyword(s):  
Molecular Docking ◽  
Dft Calculations ◽  
Cell Line ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Hct 116 ◽  
Mcf 7

In an effort to improve and achieve biologically active anticancer agents, a novel series of 1,2,3-triazole-containing hybrids were designed and efficiently synthesized via the Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction of substituted-arylazides with alkyne-functionalized pyrazole-[1,2,4]-triazole hybrids. The structure geometry of these new clicked 1,2,3-triazoles was explored by density functional theory (DFT) using the B3LYP/6-311++G(d,p) level; also, the potential activity of the compounds for light absorption was simulated by time-dependent DFT calculations (TD-DFT). The antitumor impacts of the newly synthesized compounds were in vitro estimated to be towards the human liver cancer cell line (HepG-2), the human colon cancer cell line (HCT-116), and human breast adenocarcinoma (MCF-7). Among the tested compounds, conjugate 7 was the most potent cytotoxic candidate towards HepG-2, HCT-116, and MCF-7, with IC50 = 12.22, 14.16, and 14.64 µM, respectively, in comparison to that exhibited by the standard drug doxorubicin (IC50 = 11.21, 12.46, and 13.45 µM). Finally, a molecular docking study was conducted within the epidermal growth factor receptor (EGFR) active site to suggest possible binding modes. Hence, it could conceivably be hypothesized that analogies 7, 6, and 5 could be considered as decent lead candidate compounds for anticancer agents.

scholarly journals Anticancer and molecular docking studies of some new pyrazole-1-carbothioamide nucleosides

2019 ◽  
Vol 9 (6) ◽  
pp. 4642-4648 ◽  
Keyword(s):  
Molecular Docking ◽  
Human Cancer ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Reference Drug ◽  
Human Cancer Cell Lines ◽  
Chemical Structures ◽  
Hct 116 ◽  
Mcf 7

Eight pyrazole-1-carbothioamide nucleosides were synthesized through conensation of 3-(4-aminophenyl)-pyrazole-1-carbothioamide derivative 2 with four aldoses (arabinose, mannose, glucose and galactose) and acetylation of the produced nucleosides 3a-d with acetic anhydride in pyridine at room temperature to give their corresponding acetyl derivatives 4a-d. Their chemical structures were confirmed by spectroscopic and elemental analysis. The antiproliferative activity was screened against various human cancer cell lines (MCF-7, HepG2 and HCT-116) in vitro; compound 4b showed a significant IC50 values (8.5±0.72 for MCF-7, 9.4±0.84 for HepG2 and 11.7±0.89 µg/ml for HCT-116) which were close to the reference drug 5-fluorouracil (5-FU). Molecular docking study was utilized to illustrate the ability of the more active compounds 3b and 4b to inhibit thymidylate synthase and compare the results with an antimetabolite drug used in cancer chemotherapy "Raltitrexed".

scholarly journals Design, Synthesis, Antitumor Activity and Molecular Docking Study of Novel 5-Deazaalloxazine Analogs

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2518
Author(s):  
Sawsan Mahmoud ◽  
Doaa Samaha ◽  
Mosaad S. Mohamed ◽  
Nageh A. Abou Taleb ◽  
Mohamed A. Elsawy ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Tumor Cell ◽  
Cell Lines ◽  
Antitumor Agents ◽  
Binding Free Energy ◽  
Docking Study ◽  
Tumor Cell Lines ◽  
Molecular Docking Study ◽  
Mcf 7

Protein tyrosine kinases (PTKs) are the most potential therapeutic targets for cancer. Herein, we present a sound rationale for synthesis of a series of novel 2-(methylthio), 2-(substituted alkylamino), 2-(heterocyclic substituted), 2-amino, 2,4-dioxo and 2-deoxo-5-deazaalloxazine derivatives by applying structure-based drug design (SBDD) using AutoDock 4.2. Their antitumor activities against human CCRF-HSB-2, KB, MCF-7 and HeLa have been investigated in vitro. Many 5-deazaalloxazine analogs revealed high selective activities against MCF-7 tumor cell lines (IC50: 0.17–2.17 µM) over HeLa tumor cell lines (IC50 > 100 µM). Protein kinase profiling revealed that compound 3h induced multi- targets kinase inhibition including −43% against (FAK), −40% against (CDKI) and −36% against (SCR). Moreover, the Annexin-V/PI apoptotic assay elucidate that compound 3h showed 33% and potentially 140% increase in early and late apoptosis to MCF-7 cells respectively, compared to the control. The structure-activity relationship (SAR) and molecular docking study using PTK as a target enzyme for the synthesized 7-deazaalloaxazine derivatives were investigated as potential antitumor agents. The AutoDock binding affinities of the 5-deazaalloxazine analogs into c-kit PTK (PDB code: 1t46) revealed reasonable correlations between their AutoDock binding free energy and IC50.

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.

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