Three anticancer Pt complexes with glycine derivatives: synthesis, bioactivity on MCF-7 cell line, ADME prediction, DFT, MEP, and molecular docking

2021 ◽  
Author(s):  
Mahboube Eslami Moghadam ◽  
Ameneh Jafari ◽  
Ramin Kiani Khashandaragh ◽  
Adeleh Divsalar ◽  
Mitra Ghasemzadeh
Keyword(s):  
Molecular Docking ◽  
Cell Line ◽  
Adme Prediction ◽  
Glycine Derivatives ◽  
Mcf 7

Design, synthesis, molecular docking and ADME studies of novel indole-thiazolidinedione derivatives and their antineoplastic activity as CDK6 inhibitors

2021 ◽  
Author(s):  
Zeynep Ates-Alagoz ◽  
Mehmet Murat Kisla ◽  
Fikriye Zengin Karadayi ◽  
Sercan Baran ◽  
Tuğba Somay Doğan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Line ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Antineoplastic Activity ◽  
Design Synthesis ◽  
Mcf 7

Several indole-thiazolidinedione derivatives (9–24) were designed and synthesized as CDK6 inhibitors, and their anticancer activity was probed on the MCF-7 cell line and the effects on gene expression profiles were elucidated.

scholarly journals QSAR, molecular docking, design, and pharmacokinetic analysis of 2-(4-fluorophenyl) imidazol-5-ones as anti-breast cancer drug compounds against MCF-7 cell line

2020 ◽  
Vol 52 (6) ◽  
pp. 475-494
Author(s):  
Hadiza Abdulrahman Lawal ◽  
Adamu Uzairu ◽  
Sani Uba
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Cell Line ◽  
Docking Studies ◽  
Cancer Drug ◽  
Pharmacokinetic Analysis ◽  
Analysis Model ◽  
Molecular Docking Studies ◽  
Derivatives Of ◽  
Mcf 7

AbstractThe anti-proliferative activities of Novel series of 2-(4-fluorophenyl) imidazol-5-ones against MCF-7 breast cancer cell line were explored via in-slico studies which includes Quantitative structure–activity relationship QSAR, molecular docking studies, designing new compounds, and analyzing the pharmacokinetics properties of the designed compounds. From the QSAR analysis, model number one emerged the best as seen from the arithmetic assessments of (R2) = 0.6981, (R2adj) = 0.6433, (Q2) = 0.5460 and (R2pred) of 0.5357. Model number one was used in designing new derivative compounds, with higher effectiveness against estrogen positive breast cancer (MCF-7 cell line). The Molecular docking studies between the derivatives and Polo-like kinases (Plk1) receptor proved that the derivatives of 2-(4-fluorophenyl) imidazol-5-ones bind tightly to the receptor, thou ligand 24 and 27 had the highest binding affinities of −8.8 and − 9.1 kcal/mol, which was found to be higher than Doxorubicin with a docking score of −8.0 kcal/mol. These new derivatives of 2-(4-fluorophenyl) imidazol-5-ones shall be excellent inhibitors against (plk1). The pharmacokinetics analysis performed on the new structures revealed that all the structures passed the test and also the Lipinski rule of five, and they could further proceed to pre-clinical tests. They both revealed a revolution in medicine for developing novel anti-breast cancer drugs against MCF-7 cell line.

Evaluation of Benzamide-chalcone Derivatives as EGFR/CDK2 inhibitor: Synthesis, in-vitro Inhibition, and Molecular Modeling Studies

2021 ◽  
Vol 21 ◽  
Author(s):  
Akshada Joshi ◽  
Heena Bhojwani ◽  
Ojas Wagal ◽  
Khushboo Begwani ◽  
Urmila Joshi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Line ◽  
Antiproliferative Activity ◽  
Docking Studies ◽  
Wild Type ◽  
Chalcone Derivatives ◽  
Ht 29 ◽  
Egfr Kinase ◽  
Mcf 7 ◽  
Mutant Egfr

Background: EGFR (Epidermal Growth Factor Receptor) and CDK2 (Cyclin Dependent Kinase 2) are important targets in the treatment of many solid tumors and different ligands of these receptors share many common structural features. Objective: The study involved synthesis of benzamide-substituted chalcones and determination of their antiproliferative activity as well as preliminary evaluation of EGFR and CDK2 inhibitory potential using both receptor binding and computational methods. Methods: We synthesized 13 benzamide-substituted chalcone derivatives and tested their antiproliferative activity against MCF-7, HT-29 and U373MG cell-lines using Sulforhodamine B Assay. Four compounds were examined for activity against EGFR and CDK2 kinase. The compounds were docked into both EGFR and CDK2 using Glide software. The stability of the interactions for most active compound was evaluated by Molecular Dynamics Simulation using Desmond software. Molecular Docking studies on mutant EGFR (T790M, T790M/L858R, and T790M/C797S) were also carried out. Results: From the SRB assay, we concluded that compounds 1g, and 1k were effective in inhibiting the growth of MCF-7 cell line whereas the other compounds were moderately active. Most compounds were either moderately active or inactive on U373 MG and HT-29 cell line. Compounds 1g and 1k showed good inhibitory activity against CDK2 kinase while 1d and 1f were moderately active. Compounds 1d, 1f, 1g, and 1k were moderately active against EGFR kinase. Molecular docking reveals involvement of one hydrogen bond with Met793 in binding with EGFR however; it was not stable during simulation and these compounds bind to the receptor mainly via hydrophobic contacts. This fact also points towards a different orientation of the inhibitor within the active site of EGFR kinase. Binding mode analysis for CDK2 inhibition studies indicate that hydrogen bonding interaction with Lys 33 and Leu83 are important for the activity. These interactions were found to be stable throughout the simulation. Considering the results for wild-type EGFR inhibition, the docking studies on mutants were performed and which indicate that the compounds bind to the mutant EGFR but the amino acid residues involved are similar to the wild-type EGFR and therefore, the selectivity seems to be limited. Conclusion: These benzamide-substituted chalcone derivatives will be useful as lead molecules for the further development of newer inhibitors of EGFR and/or CDK2 kinases.

scholarly journals Design, Synthesis, Molecular Docking, ADME and Biological Evaluation Studies of Some New 1,3,4-oxadiazole Linked Benzimidazoles as Anticancer Agents and Aromatase Inhibitors

2021 ◽  
Author(s):  
ulviye acar çevik ◽  
Ismail Celik ◽  
Ayşen IŞIK ◽  
Yusuf Özkay ◽  
Zafer Asım Kaplancıklı
Keyword(s):  
Molecular Docking ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Evaluation Studies ◽  
Biological Evaluation ◽  
Binding Modes ◽  
Anticancer Activities ◽  
Mcf 7

Abstract In this study, due to the potential anticancer effects of the benzimidazole ring system, a series of benzimidazole-1,3,4-oxadiazole derivatives were synthesized and characterized by 1H NMR, 13C NMR, and MS spectra analyses. In the in vitro anticancer assay, all the compounds tested anticancer activities using MTT-based assay against five cancer cell lines (MCF-7, A549, HeLa, C6, and HepG2). Among them, compound 5a exhibited the most potent activity with IC50 values of 5,165±0,211 μM and 5,995±0,264 μM against MCF-7 and HepG2 cell lines. Compound 5a was included in the BrdU test to determine the DNA synthesis inhibition effects for both cell types. Furthermore, compound 5c was also found to be more effective than doxorubicin on the HeLa cell line. The selectivity of anticancer activity was evaluated in NIH3T3 (mouse embryo fibroblast cell line) cell line. In vitro, enzymatic inhibition assays of aromatase enzyme were performed for compound 5a acting on the MCF-7 cell line. For compound 5a, in silico molecular docking against aromatase enzyme was performed to determine possible protein-ligand interactions and binding modes.

scholarly journals Benzophenone Derivatives Showed Dual Anti-Inflammatory and Antiproliferative Activities by Inhibiting COX Enzymes and Promote Cyclin E Downregulation

2022 ◽  
Author(s):  
Laís Folquitto ◽  
Thiago de Souza ◽  
Jaqueline Januario ◽  
Isadora Nascimento ◽  
Brenda Brandão ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Line ◽  
Cell Lines ◽  
Antiproliferative Activity ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Antiproliferative Activities ◽  
Mcf 7

Considering the promising antitumor effects of compounds with dual anti-inflammatory and antiproliferative activities, thus benzophenones analogs (2-7) were evaluated on in vivo antiinflammatory assay and molecular docking analysis. Those with the best molecular docking results were in vitro evaluated on cyclooxygenase (COX) enzymes and tested regarding antiproliferative activity. All derivatives displayed in vivo anti-inflammatory activity. Among them, the substances 2’-hydroxy-4’-benzoylphenyl-β-D-glucopyranoside (4), 4-hydroxy-4’-methoxybenzophenone (5) and 4’-(4’’-methoxybenzoyl)phenyl-β-D-glucopyranoside (7) showed the best values of Glide Score in COX-2 docking evaluation and 4 and 5 selectively inhibited COX-2 and COX-1 in vitro enzymatic assay, respectively. Thus, 4 and 5 were tested against breast cancer (MCF-7, MDA‑MB-231, Hs578T) and non-small-cell-lung cancer (A549) cell lines. The estrogen-positive MCF-7 cell line was more responsive compared to other tested cell lines. They induced cell cycle arrest at G1/S transition in MCF-7 cell line once there was an increase in G0/G1 population with concomitant reduction of S population. The antiproliferative activity of these substances on MCF-7 was associated with their ability to inhibit cyclin E expression, a critical regulator of G1/S transition. Taken together, the data indicate that 4 and 5 have dual anti-inflammatory and antiproliferative activities and support further studies to evaluate their antitumor potential.

scholarly journals Pharmacological Screening of Substituted 1, 4 Dihydropyrimidines

2016 ◽  
Author(s):  
◽  
Reshme Govender
Keyword(s):  
Antimicrobial Activity ◽  
Antioxidant Activity ◽  
Molecular Docking ◽  
Minimum Inhibitory Concentration ◽  
Cell Line ◽  
Inhibitory Activity ◽  
Inhibitory Concentration ◽  
Gram Positive ◽  
Anti Inflammatory ◽  
Mcf 7

Pharmacological research is essential for the advancement of treatment therapies to combat diseases that plague mankind. Pyrimidines have been a subject under investigation by medicinal chemists for many years due to their interesting pharmacological properties. In previous studies, pyrimidines and their derivatives have been reported to have antimicrobial, anti-inflammatory, antimalarial, analgesic, and antitumour activities amongst other biological activities. Although there has been a significant amount of research carried out on these heterocycles, there will always be a continuous need for the discovery of novel synthetic drugs which have a higher degree of potency and fewer side effects. Hence, this study was undertaken to determine the pharmacological activities of eight novel 1, 4 dihydropyrimidine analogues (DHPM 1 – 8), that have been synthesized in our laboratory. The dihydropyrimidines were synthesized and characterized and thereafter evaluated for in vitro antimicrobial, antioxidant, anti-inflammatory, cytotoxicity and apoptotic activities. The compounds also underwent a safety study. Antimicrobial activity was evaluated using the disk diffusion assay; compounds displaying superior activity were subjected to further analysis to establish the minimum inhibitory concentration. Overall compounds DHPM 7 and 8 showed the best antibacterial activity against Gram positive bacteria. The minimum inhibitory concentration (MIC) for DHPM 7 against the Gram positive organisms (B.cereus, S.aureus and B.coagulans) was 0.75 µg/mL; however DHPM 7 had a MIC of 0.37 µg/mL against M. luteus. DHPM 8 displayed an MIC of 0.75 µg/mL against B.cereus, S.aureus, M.luteus, S.faecalis and B.coagulans. Antioxidant activity was assessed using the DPPH method. DHPM 2 showed outstanding free radical scavenging capacity of 90.63% at a concentration of 1 mg/mL. The DHPM 1 - 8 were analysed for their lipoxygenase inhibitory activity. Excellent inhibition ranging from 59.37 ± 0.6 to 81.19 ± 0.94% was demonstrated. The inhibitory activity was elucidated by a molecular docking study against the lipoxygenase enzyme (PDB code = 3V99) using the MOE 2013.08 and Leadit 2.1.2 software and high affinities were demonstrated. DHPM 1 - 8 were tested for cytotoxic activity against two human cancer cell lines, MCF-7 and UACC-62 by means of the MTT assay. It was observed for the MCF-7 cell line, DHPM 1, 4, 6, 7 and 8 displayed cytotoxicity above 89% at 50 µg/mL. The DHPMs at 50 µg/mL were noted to be very effective against the Melanoma cell line with DHPM 2 having a cytotoxicity value of 82.62% and DHPM 1, 4, 5, 6, 7 and 8 exhibiting cytotoxicity greater than 96%. Only slight inhibition of the proliferation of PBMC’s was noted. IC50 values of DHPM 1-8 were determined and the best activity overall was displayed by DHPM 8. The IC50 of DHPM 8 was 0.92 ± 0.09 and 1.97 ± 0.08 µM against MCF - 7 and UACC - 62 cell lines, respectively. The compounds that displayed toxicity towards the UACC - 62 cell line were investigated for their apoptotic inducing potential. The apoptotic studies were performed by flow cytometry using the following assays; Annexin V, JC-1 and Caspase -3 assays. The effect of these compounds was compared to a known anti-cancer drug, Camptothecin. On evaluation of the mechanism of action of the compounds, it was found that most compounds are using apoptotic pathways for cell death. Our studies have identified antimicrobial activity (DHPM 1-8) against Gram positive organisms, high antioxidant activity (DHPM 2), anti-inflammatory activity (DHPM 1-8) and anticancer activity (DHPM 1-8) against UACC-62 and MCF-7 cells. DHPM 1-8 were found to have no toxicity at 100 µg/mL in the brine shrimp assay and hence are probably safe as therapeutic agents. Furthermore molecular docking studies confirmed the activity of DHPM 1-8 as potential lipoxygenase inhibitors. DHPM 1-8 are novel compounds with great potential to be developed into chemotherapeutic agents.

scholarly journals Synthesis, Evaluation for Cytotoxicity and Molecular Docking Studies of Benzo[c]furan-Chalcones for Potential to Inhibit Tubulin Polymerization and/or EGFR-Tyrosine Kinase Phosphorylation

2018 ◽  
Vol 19 (9) ◽  
pp. 2552 ◽  
Author(s):  
Malose Mphahlele ◽  
Marole Maluleka ◽  
Nishal Parbhoo ◽  
Sibusiso Malindisa
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Molecular Docking ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Cell Line ◽  
Receptor Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Tubulin Polymerization ◽  
Epidermal Growth ◽  
Mcf 7

A series of 2-arylbenzo[c]furan-chalcone hybrids 3a–y have been synthesized and evaluated for antiproliferative effects against the human breast cancer (MCF-7) cell line and for its potential to induce apoptosis and also to inhibit tubulin polymerization and/or epidermal growth factor receptor-tyrosine kinase (EGFR-TK) phosphorylation. Most of these compounds exhibited moderate to significant antigrowth effects in vitro against the MCF-7 cell line when compared to the reference standard actinomycin D. The capabilities of the most cytotoxic benzofuran-chalcone hybrids 3b and 3i, to induce apoptosis, have been evaluated by Annexin V-Cy3 SYTOX staining and caspase-3 activation. The experimental and molecular docking results suggest that the title compounds have the potential to exhibit inhibitory effects against tubulin polymerization and epidermal growth factor receptor tyrosine kinase (EGFR-TK) phosphorylation. The modeled structures of representative compounds displayed hydrophobic interactions as well as hydrogen and/or halogen bonding with the protein residues. These interactions are probably responsible for the observed increased binding affinity for the two receptors and their significant antigrowth effect against the MCF-7 cell line.

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

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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