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

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.

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New phosphate derivatives of betulin as anticancer agents: Synthesis, crystal structure, and molecular docking study

Bioorganic Chemistry ◽

10.1016/j.bioorg.2019.03.060 ◽

2019 ◽

Vol 87 ◽

pp. 613-628 ◽

Cited By ~ 5

Author(s):

Elwira Chrobak ◽

Monika Kadela-Tomanek ◽

Ewa Bębenek ◽

Krzysztof Marciniec ◽

Joanna Wietrzyk ◽

...

Keyword(s):

Crystal Structure ◽

Molecular Docking ◽

Anticancer Agents ◽

Docking Study ◽

Molecular Docking Study ◽

Derivatives Of

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

Royal Society Open Science ◽

10.1098/rsos.172407 ◽

2018 ◽

Vol 5 (6) ◽

pp. 172407 ◽

Cited By ~ 3

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.

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

Molecules ◽

10.3390/molecules26030708 ◽

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.

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

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200408080040 ◽

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.

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Involvement of P-gp on Reversing Multidrug Resistance Effects of 23-Hydroxybetulinic Acid on Chemotherapeutic Agents

Frontiers in Pharmacology ◽

10.3389/fphar.2021.796745 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhihao Liu ◽

Xiaozhou Wen ◽

Guangji Wang ◽

Ying Zhou

Keyword(s):

Molecular Docking ◽

Multidrug Resistance ◽

Biological Effects ◽

Docking Study ◽

Chemotherapeutic Agents ◽

Potential Interaction ◽

Molecular Docking Study ◽

Cytotoxicity Activity ◽

Mcf 7

Betulinic acid (BA) and 23-Hydroxybetulinic acid (23-HBA) are natural products with similar structures, which show a range of biological effects including cytotoxicity activity. The aim of current research was to investigate and evaluate the combinational cytotoxicity of BA and 23-HBA with chemotherapeutic agents in vitro, and to clarify the potential interaction and related mechanism with P-gp. Instead of BA, 23-HBA could increase cytotoxicity of MCF-7/ADR cells to adriamaycin (ADR) and vincristine (VCR). The intracellular accumulation of ADR/VCR in MCF-7/ADR cells was obviously increased in the presence of 23-HBA. Furthermore, 23-HBA could show dose-dependent increase on the transport of VCR and digoxin, which are typical P-gp substrates, in both MDCK-MDR1 and Caco-2 cells. However, the transport of BA and 23-HBA was not influenced by P-gp inhibition in MDCK-MDR1 cells. MDR1 shift assay and molecular docking model suggested that both compounds showed interaction with P-gp, yet the binding affinity and sites are different. In conclusion, 23-HBA could strongly improve the efficacy of anti-tumor agents in multidrug resistance (MDR) cells, which was related to P-gp inhibition. The MDR1 shift assay and molecular docking study further revealed that 23-HBA and BA showed different interaction modes with P-gp.

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

Molecules ◽

10.3390/molecules25204780 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4780 ◽

Cited By ~ 1

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.

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Molecular Docking Study for Analyzing the Inhibitory Effect of Anti-inflammatory Plant Compound Against Tumour Necrosis Factor (TNF-α)

Current Drug Therapy ◽

10.2174/1574885513666180503145352 ◽

2019 ◽

Vol 14 (1) ◽

pp. 85-90

Author(s):

Sagarika Biswas

Keyword(s):

Molecular Docking ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Docking Study ◽

Developed Countries ◽

Inhibitory Effect ◽

Molecular Docking Study ◽

Drug Designing ◽

Anti Inflammatory ◽

Necrosis Factor

Background: Rheumatoid Arthritis (RA) is an autoimmune disorder of symmetric synovial joints which is characterized by the chronic inflammation with 0.5-1% prevalence in developed countries. Presence of persistent inflammation is attributed to the major contribution of key inflammatory cytokine and tumour necrosis factor- alpha (TNF- α). Recent drug designing studies are developing TNF-α blockers to provide relief from the symptoms of the disease such as pain and inflammation. Available blockers are showing certain limitations such as it may enhance the rate of tuberculosis (TB) occurrence, lymphoma risk, cost issues and certain infections are major concern. Discussed limitations implicated a need of development of some alternative drugs which exhibit fewer side effects with low cost. Therefore, we have identified anti-inflammatory compounds in an underutilized fruit of Baccaurea sapida (B.sapida) in our previous studies. Among them quercetin have been identified as the most potent lead compound for drug designing studies of RA. Methods: In the present article, characterization of quercetin has been carried out to check its drug likeliness and molecular docking study has been carried out between TNF- α and quercetin by using AutoDock 4.2.1 software. Further, inhibitory effect of B. sapida fruit extract on RA plasma has been analysed through immunological assay ELISA. Results: Our in-silico analysis indicated that quercetin showed non carcinogenic reaction in animal model and it may also cross the membrane barrier easily. We have studied the ten different binding poses and best binding pose of TNF-α and quercetin showed -6.3 kcal/mol minimum binding energy and 23.94 µM inhibitory constant. In addition to this, ELISA indicated 2.2 down regulated expression of TNF-α in RA compared to control. Conclusion: This study may further be utilized for the drug designing studies to reduce TNF-α mediated inflammation in near future. This attempt may also enhance the utilization of this plant worldwide.

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