Synthesis, cytotoxic activity, ADMET and molecular docking study of quinoline-based hybrid compounds of 1,5-benzothiazepines

Some α,β-unsaturated ketones 4a–g of 3-acetyl-4-hydroxyquinolin-2(1H)-one were prepared and converted into a series of new hybrid compounds, quinoline-benzothiazepine 6a–g. Compounds 6d and 6g had the best activity against HepG2 and KB cell lines.

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

Molecules ◽

10.3390/molecules25030717 ◽

2020 ◽

Vol 25 (3) ◽

pp. 717 ◽

Cited By ~ 2

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.

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Nano Sb2O3 catalyzed green synthesis, cytotoxic activity, and molecular docking study of novel α-aminophosphonates

Medicinal Chemistry Research ◽

10.1007/s00044-019-02302-y ◽

2019 ◽

Vol 28 (4) ◽

pp. 528-544 ◽

Cited By ~ 5

Author(s):

Sreelakshmi Poola ◽

Maheshwara Reddy Nadiveedhi ◽

Santhisudha Sarva ◽

Mohan Gundluru ◽

Saichaithanya Nagaripati ◽

...

Keyword(s):

Molecular Docking ◽

Green Synthesis ◽

Cytotoxic Activity ◽

Docking Study ◽

Molecular Docking Study

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Acetylcholinesterase and Cytotoxic Activity of Chemical Constituents of Clutia lanceolata Leaves and its Molecular Docking Study

Natural Products and Bioprospecting ◽

10.1007/s13659-016-0110-x ◽

2016 ◽

Vol 6 (6) ◽

pp. 267-278 ◽

Cited By ~ 7

Author(s):

Mehtab Parveen ◽

Faheem Ahmad ◽

Ali Mohammed Malla ◽

Shaista Azaz ◽

Mahboob Alam ◽

...

Keyword(s):

Molecular Docking ◽

Cytotoxic Activity ◽

Chemical Constituents ◽

Docking Study ◽

Molecular Docking Study

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

Molecules ◽

10.3390/molecules24061066 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1066 ◽

Cited By ~ 10

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.

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Novel 4-thiazoline-coumarin hybrid compounds containing sugar moieties: Synthesis, biological evaluation and molecular docking study as antiproliferative agents

New Journal of Chemistry ◽

10.1039/d1nj00680k ◽

2021 ◽

Author(s):

Ngoc Toan Vu ◽

Nguyen Dinh Thanh

Keyword(s):

Molecular Docking ◽

Human Liver ◽

Docking Study ◽

Biological Evaluation ◽

Breast Adenocarcinoma ◽

Molecular Docking Study ◽

Antiproliferative Agents ◽

Hybrid Compounds ◽

Human Liver Cancer ◽

Mcf 7

A new series of 2,3-4-thiazoline−coumarin hybrid compounds that contained D-glucose and D-galactose moieties (4a-g) were synthesized and evaluated their cytotoxic activity against breast adenocarcinoma (MCF-7), human liver cancer (HepG2), human...

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

Crystals ◽

10.3390/cryst10060446 ◽

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.

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