scholarly journals Synthesis and molecular docking studies of some novel Schiff bases incorporating 6-butylquinolinedione moiety as potential topoisomerase IIβ inhibitors

2018 ◽  
Vol 5 (6) ◽  
pp. 172407 ◽  
Author(s):  
Hany M. Hassanin ◽  
Rabah A. T. Serya ◽  
Wafaa R. Abd Elmoneam ◽  
Mai A. Mostafa
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Docking Study ◽  
Docking Studies ◽  
Complex Compounds ◽  
Inhibition Activity ◽  
Molecular Docking Study ◽  
Dna Topoisomerase ◽  
Mcf 7

A series of novel pyranoquinolinone-based Schiff's bases were designed and synthesized. They were evaluated for topoisomerase IIβ (TOP2B) inhibitory activity, and cytotoxicity against breast cancer cell line (MCF-7) for the development of novel anticancer agents. A molecular docking study was employed to investigate their binding and functional properties as TOP2B inhibitors, using the D iscovery S tudio 2.5 software, where they showed very interesting ability to intercalate the DNA–topoisomerase complex. Compounds 2a , 2c and 2f showed high docking score values (82.36% −29.98 kcal mol −1 for compound 2a , 78.18% −26.98 kcal mol −1 for compound 2c and 78.65, −28.11 kcal mol −1 for compound 2f ) and revealed the highest enzyme inhibition activity. The best hit compounds exhibited highly potent TOP2B inhibitors with submicromolar IC50 at 5 µM compared to the reference doxorubicin.

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 INDOLE DERIVATIVES: DESIGN, SYNTHESIS, IN-VITRO BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY AS ANTICANCER AGENTS

2018 ◽  
Vol 5 (1) ◽  
pp. 28-32
Author(s):  
Amuthavalli A ◽  
Prakash B ◽  
Velmurugan R
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Docking Study ◽  
Docking Studies ◽  
Biological Evaluation ◽  
In Vitro Cytotoxicity ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Standard Drug

New hetero annulated indoles were synthesized and structurally characterized by spectral means. In order to understand the nature of interactions of these molecules, we carried out molecular docking studies using the protein kinase CK2 inhibitors. The docking results provided some useful information for the futuredesign of more potent inhibitors. The in vitro cytotoxicity was evaluated for all the new compounds by MTT assay against HeLa and compared with the standard drug ellipticine. All the compounds showed moderate to potent activity against the cell lines. The preliminary structure–activity relationships were carried out.

Molecular Docking Study of Active Diazenyl Scaffolds as Inhibitors of Essential Targets Towards Antimicrobial Drug Discovery

2019 ◽  
Vol 20 (15) ◽  
pp. 1587-1602 ◽  
Author(s):  
Harmeet Kaur ◽  
Sudhir Gahlawat ◽  
Jasbir Singh ◽  
Balasubramanian Narasimhan
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Schiff Bases ◽  
Docking Study ◽  
Docking Studies ◽  
Binding Energies ◽  
Antifungal Drugs ◽  
Molecular Docking Study ◽  
Dna Topoisomerase ◽  
Standard Drug

Background: The diazenyl compounds (-N=N- linkage) have been reported to have antimicrobial activity. In modern drug discovery, the drug-receptor interactions are generally explored by the molecular docking studies. Materials and Methods: Three categories of diazenyl scaffolds were screened for the docking studies to explore the binding mechanism of interaction with various microbial targets. The diazenyl Schiff bases (SBN-20, SBN-21, SBN-25, SBN-33, SBN-39, SBN-40 and SBN-42), naphthol pharmacophore based diazenyl Schiff bases (NS-2, NS-8, NS-12, NS-15, NS-21, and NS-23), morpholine based diazenyl chalcones (MD-6, MD-9, MD-14, MD-16, MD-20, and MD-21) were docked against various bacterial and fungal proteins in comparison with different standard drugs. Further, the drug likeliness and ADME properties of these molecules were predicted by QikProp module of the Schrodinger software. Results: Most of the derivatives had shown less docking scores and binding energies towards bacterial proteins, such as dihydropteroate synthase (PDB:2VEG), glucosamine-6-phosphate synthase (PDB:2VF5), dihydrofolate reductase (PDB:3SRW) in comparison with the standard drugs. The naphthol based diazenyl Schiff bases NS-21 and NS-23 were predicted to act on the cytochrome P450 sterol 14-alpha-demethylase (CYP51) (PDB:5FSA) involved in sterol biosynthesis, an essential target for antifungal drugs. The derivative MD-6, NS-2, NS-21, and NS-23 had shown high docking scores against bacterial DNA topoisomerase (PDB:3TTZ) in comparison with the standard drug ciprofloxacin. Further, most of the synthesized derivatives had shown drug like characters. Conclusion: Hence, these compounds can be developed as novel antibacterial agents as potent DNA topoisomerase inhibitors and antifungal agents as CYP51 inhibitors.

Divergent de novo synthesis of 2,4,5-trideoxyhexopyranosides derivatives of podophyllotoxin as anticancer agents

2019 ◽  
Vol 11 (23) ◽  
pp. 3015-3027 ◽  
Author(s):  
Yapeng Lu ◽  
Lu Wang ◽  
Xinyang Wang ◽  
Haoliang Yuan ◽  
Yu Zhao
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
De Novo ◽  
Docking Study ◽  
Inhibitory Effect ◽  
De Novo Synthesis ◽  
Molecular Docking Study ◽  
Cytotoxicity Activity ◽  
Derivatives Of ◽  
Mcf 7

Aim: Identification of new anticancer glycosidic derivatives of podophyllotoxin. Methods: 14 podophyllotoxin D- and L-monosaccharides have been synthesized in three steps employing de novo glycosylation strategy, and their abilities to inhibit the growth of HeLa, HepG2, MCF-7, A549 and MDA-MB-231 cancer cells were investigated by MTT assay. Molecular docking study of compound 5j with tubulin was performed. Immunofluorescence was applied for detecting the inhibitory effect of 5j on tubulin polymerization. Results & conclusion: Most of synthesized compounds showed strong cytotoxicity activity against five cancer cell lines. Compound 5j possessed the highest cytotoxicity with the IC50 values from 41.6 to 95.2 nM, and could concentration-dependently inhibit polymerization of the microtubule cytoskeleton of MCF-7 cells. Molecular docking disclosed that sugar moiety-dedicated hydrogen bond endowed 5j a higher binding affinity for tubulin.

scholarly journals In silico Assessment and Molecular Docking Studies of Some Phyto-Triterpenoid for Potential Disruption of Mortalin-p53 Interaction

Processes ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1983
Author(s):  
Minh Quan Pham ◽  
Thuy Huong Le Thi ◽  
Quoc Long Pham ◽  
Le Thi Le ◽  
Huy Toan Dao ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Transcriptional Activation ◽  
Docking Study ◽  
Docking Studies ◽  
Common Type ◽  
Inhibition Activity ◽  
Molecular Docking Study ◽  
Chemotherapy Drugs ◽  
Anti Cancer ◽  
Pharmacokinetic Properties

Human hepatocellular carcinoma (HCC), the most common type of liver cancer, represents the second most common cause of death from cancer worldwide. The high toxicity and side effects of some cancer chemotherapy drugs increase the demand for new anti-cancer drugs from natural products. Mortalin/mtHsp70, a stress response protein, has been reported to contribute to the process of carcinogenesis in several ways, including the inhibition of the transcriptional activation of p53. This study conducted a molecular docking study of 41 phyto triterpenes originated from Vietnamese plants for potential Mortalin inhibition activity. Nine compounds were considered as promising inhibitors based on the analysis of binding affinity and drug-like and pharmacokinetic properties.

Discovery of a Highly Potent and Novel Gambogic Acid Derivative as an Anticancer Drug Candidate

2020 ◽  
Vol 20 ◽  
Author(s):  
Huiping Ling ◽  
Hong Li ◽  
Meijun Chen ◽  
Baolong Lai ◽  
Haiming Zhou ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Anticancer Agents ◽  
Docking Study ◽  
Gambogic Acid ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Discovery Studio ◽  
Mcf 7

Background and Purpose: Gambogic acid (GA), a promising anti-cancer agent isolated from the resin of Garcinia species in Southeast Asia, exhibits high potency in inhibiting a wide variety of cancer cells growth. Moreover, the fact that it is amenable to chemical modification makes GA an attractive molecule for the development of anticancer agents. Methods: Gambogic acid-3-(4-pyrimidinyloxy) propyl ester (compound 4) was derived from the reaction between 4-hydroxypropoxy pyrimidine and GA. Its structure was elucidated by comprehensive analysis of ESIMS, HRESIMS, 1 D NMR data. Antitumor activities of compound 4 and GA in vitro against HepG-2, A549 and MCF-7 cells were investigated by MTT assay. FITC/PI dye were used to test apoptosis. The binding affinity difference of compound 4 and GA binding to IKKβ was studied by using Discovery Studio 2016. Results: Compound 4 was successfully synthesized and showed strong inhibitory effects on HepG-2, A549 and MCF-7 cells lines with IC50 value of 1.49 ± 0.11, 1.37 ± 0.06 and 0.64 ± 0.16μM, respectively. Molecular docking study demonstrated that four more hydrogen bonds were established between IKKβ and compound 4, compared with GA. Conclusion: Our results suggested that compound 4 showed significant effects in inducing apoptosis. Further molecular docking study indicated that the introduction of pyrimidine could improve GA’s binding affinity to IKKβ. Compound 4 may serve as a potential lead compound for the development of new anticancer drugs.

scholarly journals Synthesis, In Silico and In Vitro Assessment of New Quinazolinones as Anticancer Agents via Potential AKT Inhibition

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4780 ◽  
Author(s):  
Ahmed A. Noser ◽  
Mohamed El-Naggar ◽  
Thoria Donia ◽  
Aboubakr H. Abdelmonsef
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Homo Sapiens ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Docking Simulations ◽  
Ic50 Values ◽  
Quinazolinone Derivatives ◽  
Mcf 7

A series of novel quinazolinone derivatives (2–13) was synthesized and examined for their cytotoxicity to HepG2, MCF-7, and Caco-2 in an MTT assay. Among these derivatives, compounds 4 and 9 exhibited significant cytotoxic activity against Caco-2, HepG2, and MCF-7 cancer cells. Compound 4 had more significant inhibitory effects than compound 9 on Caco-2, HepG2, and MCF-7 cell lines, with IC50 values of 23.31 ± 0.09, 53.29 ± 0.25, and 72.22 ± 0.14µM, respectively. The AKT pathway is one of human cancer’s most often deregulated signals. AKT is also overexpressed in human cancers such as glioma, lung, breast, ovarian, gastric, and pancreas. A molecular docking study was performed to analyze the inhibitory action of newly synthetic quinazolinone derivatives against Homo sapiens AKT1 protein. Molecular docking simulations were found to be in accordance with in vitro studies, and hence supported the biological activity. The results suggested that compounds 4 and 9 could be used as drug candidates for cancer therapy via its potential inhibition of AKT1 as described by docking study.

scholarly journals Interaction between DNA, Albumin and Apo-Transferrin and Iridium(III) Complexes with Phosphines Derived from Fluoroquinolones as a Potent Anticancer Drug

2021 ◽  
Vol 14 (7) ◽  
pp. 685
Author(s):  
Sandra Amanda Kozieł ◽  
Monika Katarzyna Lesiów ◽  
Daria Wojtala ◽  
Edyta Dyguda-Kazimierowicz ◽  
Dariusz Bieńko ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Serum Proteins ◽  
Docking Study ◽  
Minor Groove ◽  
Docking Studies ◽  
Minor Groove Binding ◽  
Binding Modes ◽  
Groove Binding ◽  
Molecular Docking Study ◽  
Threading Intercalation

A group of cytotoxic half-sandwich iridium(III) complexes with aminomethyl(diphenyl)phosphine derived from fluoroquinolone antibiotics exhibit the ability to (i) accumulate in the nucleus, (ii) induce apoptosis, (iii) activate caspase-3/7 activity, (iv) induce the changes in cell cycle leading to G2/M phase arrest, and (v) radicals generation. Herein, to elucidate the cytotoxic effects, we investigated the interaction of these complexes with DNA and serum proteins by gel electrophoresis, fluorescence spectroscopy, circular dichroism, and molecular docking studies. DNA binding experiments established that the complexes interact with DNA by moderate intercalation and predominance of minor groove binding without the capability to cause a double-strand cleavage. The molecular docking study confirmed two binding modes: minor groove binding and threading intercalation with the fluoroquinolone part of the molecule involved in pi stacking interactions and the Ir(III)-containing region positioned within the major or minor groove. Fluorescence spectroscopic data (HSA and apo-Tf titration), together with molecular docking, provided evidence that Ir(III) complexes can bind to the proteins in order to be transferred. All the compounds considered herein were found to bind to the tryptophan residues of HSA within site I (subdomain II A). Furthermore, Ir(III) complexes were found to dock within the apo-Tf binding site, including nearby tyrosine residues.

Selection of oxypeucedanin as a potential antagonist from molecular docking analysis of HSP90

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Joshua Oluwasegun Bamidele ◽  
George Oche Ambrose ◽  
Oluwaseun Suleiman Alakanse
Keyword(s):  
Molecular Docking ◽  
Liver Toxicity ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Computational Docking ◽  
Drug Candidates ◽  
Expression Rate ◽  
Client Proteins

AbstractHSP90 is observed as one of the copious molecular chaperones that play a key role in mediating appropriate folding, maturation, and firmness of many client proteins in cells. The expression rate of HSP90 in cancer cells is at a level of 2- to 10-fold higher than the 1- to 2-fold of its unstressed and healthy ones. To combat this, several inhibitors to HSP90 protein have been studied (such as geldanamycin and its derivative 17-AAG and 17-DMAG) and have shown some primary side effects including plague, nausea, vomiting, and liver toxicity, hence the search for the best-in-class inhibitor for this protein through in silico. This study is aimed at analyzing the inhibitory potency of oxypeucedanin-a furocoumarin derivations, which have been reported to have antipoliferative activity in human prostrate carcinoma DN145 cells, and three other drug candidates retrieved from the literature via computational docking studies. The results showed oxypeucedanin as the compound with the highest binding energy of −9.2 kcal/mol. The molecular docking study was carried out using PyRx, Auto Dock Vina option, and the target was validated to confirm the proper target and the docking procedure employed for this study.

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