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

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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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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Design, Synthesis and Biological Potential of 5-(2-Amino-6-(3/4-bromophenyl)pyrimidin-4-yl)benzene-1,3-diol Scaffolds as Promising Antimicrobial and Anticancer Agents

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557518666181009141924 ◽

2019 ◽

Vol 19 (10) ◽

pp. 851-864 ◽

Cited By ~ 1

Author(s):

Sanjiv Kumar ◽

Balasubramanian Narasimhan ◽

Siong Meng Lim ◽

Kalavathy Ramasamy ◽

Vasudevan Mani ◽

...

Keyword(s):

Cell Line ◽

Cancer Cell ◽

Anticancer Agents ◽

Cancer Cell Line ◽

Docking Study ◽

Binding Pocket ◽

Dilution Method ◽

Molecular Docking Study ◽

Design Synthesis ◽

Biological Potential

Background: A series of 5-(2-amino-6-(3/4-bromophenyl)pyrimidin-4-yl)benzene-1,3-diol scaffolds was synthesized by Claisen-Schmidt condensation and characterized by NMR, IR, Mass and elemental analyses. Methods: The synthesized pyrimidine scaffolds were screened for their antimicrobial activity by tube dilution method as well for antiproliferative activity (human colorectal (HCT116) cancer cell line) by SRB assay. Results: The antimicrobial screening results demonstrated that compounds, k6, k12, k14 and k20 were found to be the most potent ones against selected microbial species. The anticancer screening results indicated that compounds, k8 and k14 displayed potent anticancer activity against cancer cell line (HCT116). Conclusion: Further, the molecular docking study carried to find out the interaction between active pyrimidine compounds with CDK-8 protein indicated that compound k14 showed best dock score with better potency within the ATP binding pocket and may be used as a lead for rational drug designing of the anticancer molecule.

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SYNTHESIS, MOLECULAR DOCKING AND ANTI-PROLIFERATIVE ACTIVITY OF NEW SERIES OF 1-METHYLSULPHONYL-3-INDOLYL HETEROCYCLES

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i12.14841 ◽

2016 ◽

Vol 8 (12) ◽

pp. 113 ◽

Cited By ~ 2

Author(s):

Heba M. Abo-salem ◽

Khadiga M. Ahmed ◽

Salwa El- Hallouty ◽

Eslam R. El-sawy ◽

Adel H. Mandour

Keyword(s):

Molecular Docking ◽

Carbonic Anhydrase ◽

Cell Line ◽

Cancer Cell ◽

Active Site ◽

Proliferative Activity ◽

Cancer Cell Line ◽

Docking Study ◽

Molecular Docking Study ◽

Ca Ix

Objective: The present work aimed to synthesize a new series of 1-methylsulphonyl-3-indolyl heterocycles and study their cytotoxic activity. In addition, we attempted to explore the mode of the interaction of anti-proliferative compounds with the active site of carbonic anhydrase IX (CA IX) theoretically via molecular docking study.Methods: Novel series of pyrazole, pyrimidine and triazole derivatives bearing 1-methylsulphonyl-1H-indole were prepared via a series of hetero cyclization reactions utilizing 3-(1-methylsulphonyl-1H-indol-3-yl)-1-(substituted phenyl)-1H-pyrazole-4-carboxaldehydes 3a-d and 3-chloro-3-(1-methylsulphonyl-1H-indol-3-yl)propenal (6) and evaluating their anti-proliferative activity. The structures of the newly synthesized compounds were confirmed by elemental analyses, IR, NMR and mass spectral data. In addition, molecular docking study of the most promising antiproliferative compounds against the active site of carbonic anhydrase IX (PDB ID: 4BCW) theoretically is discussed.Results: Compounds 5c, 7 and 12 revealed potent anti-proliferative effects against A-549 cancer cell line with IC50 of 44.3, 17.2 and 38.7 µmol/l, respectively compared to the reference drug doxorubicin (IC50 of 48.8 µmol/l). While compound 5c was found to be highly active with IC50 of 5.66 µmol/l against HCT-116 cancer cell line than doxorubicin (IC50 of 65.00 µmol/l).Conclusion: Further work is recommended to confirm the inhibition of CA IX in a specific bioassay.

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Bimetallic Iron–Palladium Catalyst System as a Lewis-Acid for the Synthesis of Novel Pharmacophores Based Indole Scaffold as Anticancer Agents

Molecules ◽

10.3390/molecules26082212 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2212

Author(s):

Mohammad Shahidul Islam ◽

M. Ali ◽

Abdullah Mohammed Al-Majid ◽

Abdullah Saleh Alamary ◽

Saeed Alshahrani ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Palladium Catalyst ◽

Cancer Cell Line ◽

Catalyst System ◽

Mcf 7 ◽

Iron Palladium

The Friedel–Crafts reaction between substituted indoles as nucleophiles with chalcones-based benzofuran and benzothiophene scaffolds was carried out by employing a highly efficient bimetallic iron–palladium catalyst system. This catalytic approach produced the desired bis-heteroaryl products with low catalyst loading, a simple procedure, and with acceptable yield. All synthesized indole scaffolds 3a–3s were initially evaluated for their cytotoxic effect against human fibroblast BJ cell lines and appeared to be non-cytotoxic. All non-cytotoxic compounds 3a–3s were then evaluated for their anticancer activities against cervical cancer HeLa, prostate cancer PC3, and breast cancer MCF-7 cell lines, in comparison to standard drug doxorubicin, with IC50 values 1.9 ± 0.4 µM, 0.9 ± 0.14 µM and 0.79 ± 0.05 µM, respectively, and appeared to be moderate to weak anticancer agents. Fluoro-substituted chalcone moiety-containing compounds, 3b appeared to be the most active member of the series against cervical HeLa (IC50 = 8.2 ± 0.2 µM) and breast MCF-7 cancer cell line (IC50 = 12.3 ± 0.04 µM), whereas 6-fluroindol-4-bromophenyl chalcone-containing compound 3e (IC50 = 7.8 ± 0.4 µM) appeared to be more active against PC3 prostate cancer cell line.

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Synthesis and Experimental Validation of New Designed Heterocyclic Compounds with Antiproliferative Activity versus Breast Cancer Cell Lines MCF-7 and MDA-MB-231

Journal of Chemistry ◽

10.1155/2017/9729284 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Vincenza Barresi ◽

Carmela Bonaccorso ◽

Domenico A. Cristaldi ◽

Maria N. Modica ◽

Nicolò Musso ◽

...

Keyword(s):

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Cancer Cell Line ◽

Breast Cancer Cell Lines ◽

Design And Synthesis ◽

Human Breast Cell ◽

Mcf 7

Recent drug discovery efforts are highly focused towards identification, design, and synthesis of small molecules as anticancer agents. With this aim, we recently designed and synthesized novel compounds with high efficacy and specificity for the treatment of breast tumors. Based on the obtained results, we constructed a Volsurf+ (VS+) model using a dataset of 59 compounds able to predict the in vitro antitumor activity against MCF-7 cancer cell line for new derivatives. In the present paper, in order to further verify the robustness of this model, we report the results of the projection of more than 150 known molecules and 9 newly synthesized compounds. We predict their activity versus MCF-7 cell line and experimentally verify the in silico results for some promising chosen molecules in two human breast cell lines, MCF-7 and MDA-MB-231.

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Evaluation of Synthetic 2,4-Disubstituted-benzo[g]quinoxaline Derivatives as Potential Anticancer Agents

Pharmaceuticals ◽

10.3390/ph14090853 ◽

2021 ◽

Vol 14 (9) ◽

pp. 853

Author(s):

Islam Zaki ◽

Sara A. Abu El-ata ◽

Eman Fayad ◽

Ola A. Abu Ali ◽

Ali H. Abu Almaaty ◽

...

Keyword(s):

Cell Line ◽

Cancer Cell ◽

Anticancer Agents ◽

Cancer Cell Line ◽

Cell Cycle Profile ◽

Quinoxaline Derivatives ◽

New Compounds ◽

Potent Inhibitory Activity ◽

Mcf 7

A new series of 2,4-disubstituted benzo[g]quinoxaline molecules have been synthesized, using naphthalene-2,3-diamine and 1,4-dibromonaphthalene-2,3-diamine as the key starting materials. The structures of the new compounds were confirmed by spectral data along with elemental microanalyses. The cytotoxic activity of all synthesized benzo[g]quinoxaline derivatives was assessed in vitro against the breast MCF-7 cancer cell line. The tested molecules revealed good cytotoxicity toward the breast MCF-7 cancer cell line, especially compound 3. The results of topoisomerase IIβ inhibition assay revealed that compound 3 exhibits potent inhibitory activity in submicromolar concentration. Additionally, compound 3 was found to cause pre-G1 apoptosis, and slightly increase the cell population at G1 and S phases of the cell cycle profile in MCF-7 cells. Finally, compound 3 induces apoptosis via Bax activation and downregulation of Bcl2, as revealed by ELISA assay.

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Half-lantern Cyclometalated Platinum(II) Complexes as Anticancer Agents: Molecular docking, Apoptosis, Cell Cycle Analysis and Cytotoxic Activity Evaluations

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210713112105 ◽

2021 ◽

Vol 21 ◽

Author(s):

Fatemeh Hajipour ◽

Masoud Mahdavinia ◽

Masood Fereidoonnezhad

Keyword(s):

Cell Cycle ◽

Molecular Docking ◽

Comet Assay ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Human Lung ◽

Cancer Cell Line ◽

Cell Cycle Analysis ◽

Mcf 7

Background and Objective: In the design of modern metal-based anticancer drugs, platinum-based complexes have gained growing interest. In this study, the anticancer activity of half-lantern cyclometalated Pt(II)‒Pt(II) complexes were was evaluated using MTT, apoptosis, cell cycle analysis, and DNA binding studies. Materials and Methods: The cytotoxicity of Pt(II)‒Pt(II) complexes were evaluated against different cancer cell lines such as human lung (A549), breast (MCF-7, and MDA-MB-231), ovarian (SKOV-3), and colon (HT-29) as well as normal breast (MCF-10A), and human lung fibroblast MRC-5 cells using MTT assay. BioLegend's PE Annexin V Apoptosis Detection Kit with 7AAD was applied to assess the apoptotic effects of 1A, and 1B compound against MCF-7, and A549 cell lines. Cell cycle analysis was determined using the flowcytometry method. The interaction of compounds with four different DNA structures with PDB codes (1BNA, 1LU5, 3CO3, and 198D) has been investigated by molecular docking. To achieve binding to DNA experimentally, the electrophoresis mobility shift assay and comet assay was applied. Results: In the evaluation of cytotoxic effects, 1A showed the highest cytotoxicity among the studied compounds, and it showed higher potency with more selectivity against normal cell lines than cisplatin. This compound had IC50 of 7.24, 2.21, 1.18, 2.71, 10.65, 18.32 and 49.21 μM against A549, SKOV3, HT29, MCF-7, MDA-MB-231, MRC-5, and MCF-10A, respectively, whereas cisplatin had IC50 of 9.75, 19.02, 107.23, 15.20, 18.09, 14.36, and 24.21 μm, respectively, on the same cell lines. In order to check the DNA binding activity of 1A, and 1B, electrophoretic mobility was also conducted, which indicated that the binding of these compounds led to a slight change in electrophoretic mobility to DNA. The migration of chromosomal DNA from the nucleus in the form of a tail or comet was executed in the comet assay of 1A on MCF-7. Examination of apoptosis of 1A, and 1B on the MCF-7 cancer cell line, showed that it could increase induction of apoptosis in this cancerous cell in a concentration-dependent manner. Investigating the effect of 1A using cell cycle analysis on MCF-7 cancer cell line showed that this complex affects the stage G1 and S of the cell cycle. Conclusion: 1A has the potential to play a significant role in future biopharmaceutical studies.

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Synthesis, Characterization, Antimicrobial Activity and Anticancer of Some New Pyrazolo[1,5-a]pyrimidines and Pyrazolo[5,1-c]1,2,4-triazines

Medicinal Chemistry ◽

10.2174/1573406415666190620144404 ◽

2020 ◽

Vol 16 (6) ◽

pp. 750-760

Author(s):

Mona A. Hosny ◽

Yasser H. Zaki ◽

Wafaa A. Mokbel ◽

Abdou O. Abdelhamid

Keyword(s):

Cell Line ◽

Cancer Cell ◽

Cancer Cell Line ◽

Antimicrobial Activities ◽

Viability Assay ◽

Active Methylene Compounds ◽

Hct 116 ◽

Active Methylene ◽

Mcf 7

Background: Pyrazole and its derivatives are known to exhibit significant biological and pharmacological activities such as anticancer, anti-inflammatory, antioxidant, antibacterial, analgesic, antiviral, antimicrobial, antifungal, anti-glycemic, antiamoebic, and antidepressive. Considering the immense biological properties, pyrazole is one of the most widely studied nitrogen- containing heterocyclic nuclei. Fused pyrazole derivatives are composed of the pyrazole nucleus attached to other heterocyclic moieties. Objective: The objective of this article is the synthesis of some new pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c]1,2,4-triazine derivatives with potential anticancer and antimicrobial activities. Methods: The in vitro growth inhibitory rates (%) and inhibitory growth activity (as measured by IC50) of the newly synthesized compounds were determined against the MCF-7 human breast carcinoma cell line in comparison with the well-known anticancer drug doxorubicin as the standard, using the MTT viability assay. The data generated were used to plot a dose-response curve from which the concentration (μM) of tested compounds required to kill 50% of the cell population (IC50) was determined. Cytotoxic activity was expressed as the mean IC50 of three independent experiments. The difference between inhibitory activities of all compounds with different concentrations was statistically significant p < 0.001. All compounds were structurally characterized by different spectroscopic techniques EI-MS, 1H-NMR, and 13C-NMR, and evaluated for their anticancer and antimicrobial activities (antibacterial and antifungal). Results: Several pyrazolo[1,5-a]pyrimidine derivatives were synthesized from the reaction of 2-(4- (5-amino-1H-pyrazol-3-yl)phenyl)-1H-indene-1,3(2H)-dione with the appropriate active methylene compounds in boiling ethanol. Also, pyrazolo[5,1-c]triazines were obtained through the reaction of 2-(4-(5-(chlorodiazenyl)-1H-pyrazol-3-yl)phenyl)-1H-indene-1,3(2H)-dione with various active methylene compounds in ethanol containing sodium acetate at 0-5 °C. The structures of the newly synthesized compounds were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic routes whenever possible. The newly synthesized compounds were evaluated for their antitumor activity against a breast cancer cell line (MCF-7) and a human colon cancer cell line (HCT-116). The results revealed that the tested compounds showed high variation in the inhibitory growth rates and activities against the tested tumor cell lines. All newly synthesized compounds screen towards microorganisms e.g. Gram-negative bacteria, Gram-positive bacteria, and Fungi. Conclusions: 2-(4-(5-Amino-1H-pyrazol-3-yl)phenyl)isoindoline-1,3-dione proved to be a useful precursor for the synthesis of various pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c]-1,2,4- triazines. The structures of the newly synthesized compounds were confirmed by spectral data and elemental analyses. The newly synthesized compounds were tested in vitro against the MCF-7, HCT-116 human cancer cell line and compared with doxorubicin as the standard, using the MTT viability assay. Most of the tested compounds were found to have moderate to high anticancer activity.

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

Future Medicinal Chemistry ◽

10.4155/fmc-2018-0593 ◽

2019 ◽

Vol 11 (23) ◽

pp. 3015-3027 ◽

Cited By ~ 2

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.

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Synthesis, Molecular Docking, And Antitumor Evaluation of Some New Pyrazole, Pyridine, And Thiazole Derivatives Incorporating Sulfonamide Residue

10.21203/rs.3.rs-792605/v1 ◽

2021 ◽

Author(s):

Sameh Elgogary ◽

Ibrahim Radini

Keyword(s):

Breast Cancer ◽

Molecular Docking ◽

Cell Line ◽

Cancer Cell ◽

Cancer Cell Line ◽

Thiazole Derivatives ◽

Standard Drug ◽

Ic50 Values ◽

Antitumor Evaluation ◽

Mcf 7

Abstract Cancer is the second leading cause of death worldwide. There is always a huge demand for novel anticancer. New series of pyrazole, pyridine, thiazole derivatives containing sulfonamide moiety were prepared and screened for their antitumor activity against breast cancer cell line (MCF-7). The results of this investigation revealed that compounds 3 and 8 had significant anticancer activity against the MCF-7 cancer cell line with IC50 values 19.2 and 14.2 μM, respectively, in relation to the standard drug, doxorubicin.

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