Synthesis and molecular docking studies of new furochromone derivatives as p38α MAPK inhibitors targeting human breast cancer MCF-7 cells

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.

Download Full-text

Design, Synthesis, In Silico and In Vitro Evaluation of Novel Pyrimidine Derivatives as EGFR Inhibitors

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200721102726 ◽

2020 ◽

Vol 20 ◽

Author(s):

Gurubasavaraja S.P. Matada ◽

Nahid Abbas ◽

Prasad S. Dhiwar ◽

Rajdeep Basu ◽

Giles Devasahayam

Keyword(s):

Breast Cancer ◽

Molecular Docking ◽

Anticancer Activity ◽

In Silico ◽

Docking Studies ◽

Breast Cancer Cell Lines ◽

Pyrimidine Derivatives ◽

Molecular Docking Studies ◽

Mcf 7

Background: The abnormal signaling from tyrosine kinase causes many types of cancers namely breast cancer, non-small cell lung cancer, and chronic myeloid leukemia. This research reports the in-silico, synthesis, and in-vitro study of novel pyrimidine derivatives as EGFR inhibitors. Objective: The objective of the research study is to discover more promising lead compounds using drug discovery process, in which the rational drug design is achieved by the molecular docking and virtual pharmacokinetic studies. Methods: The molecular docking studies were carried out using discovery studio 3.5-version software. The molecules with good docking and binding energy score were synthesized as well as their structures were confirmed by FT-IR, NMR, Mass and elemental analysis. Subsequently molecules were evaluated for their anticancer activity using MDA-MB-231, MCF-7 and A431 breast cancer cell lines by MTT and tyrosine kinase assay methodology. Results: Pyrimidine derivatives displayed anticancer activity. Particularly, compound R8 shows significant cytotoxicity against MDA-MB-231 with an IC50 18.5 ± 0.6 µM. Molecular docking studies proved that the compound R8 has good binding fitting by forming hydrogen bonds with amino acid residues at ATP binding sites of EGFR. Conclusion: Eight pyrimidine derivatives were designed, synthesized and evaluated against breast cancer cell lines. Compound R8 significantly inhibited the growth of MDA-MB-231 and MCF-7. Molecular docking studies reveled that compound R8 has good fitting by forming different Hydrogen bonding interactions with amino acids at ATP binding site of epidermal growth factor receptor target. Compound R8 was a promising lead molecule that showed better results as compared to other compounds in in-vitro studies.

Download Full-text

Potentially antibreast cancer enamidines via azide–alkyne–amine coupling and their molecular docking studies

RSC Advances ◽

10.1039/c6ra20583f ◽

2016 ◽

Vol 6 (93) ◽

pp. 90597-90606 ◽

Cited By ~ 9

Author(s):

Prakash Bansode ◽

Jagannath Jadhav ◽

Rajanikant Kurane ◽

Prafulla Choudhari ◽

Manish Bhatia ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Docking ◽

Cell Line ◽

Breast Cancer Cell ◽

Breast Cancer Cell Line ◽

Human Breast Cancer ◽

Cancer Cell Line ◽

Docking Studies ◽

Human Breast Cancer Cell ◽

Human Breast

Potentially antibreast cancer enamidines were synthesized and evaluated against human breast cancer cell line MCF7 displaying GI50values lower than doxorubicin.

Download Full-text