Synthesis of a new series of pyrimidine derivatives: exploration of anti-proliferative activity on EAT cells and molecular docking

Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women next to skin cancer. Estrogen receptors (ERs) play an important role in the progression of BC. Current anticancer agents have several drawbacks such as serious side effects and the emergence of resistance to chemotherapeutic drugs. As coumarins possess minimum side effect along with multi-drug reversal activity, it has a tremendous ability to regulate a diverse range of cellular pathways that can be explored for selective anticancer activity. Objectives: Synthesis and evaluation of new coumarin analogues for anti-proliferative activity on human breast cancer cell line MCF-7 along with exploration of binding interaction of the compounds for ER-α target protein by molecular docking. Method: In this study, the anti-proliferative activity of C-3 substituted coumarins analogues (1-17) has been evaluated against estrogen receptor-positive MCF-7 breast cancer cell lines. Molecular interactions and ADME study of the compounds were analyzed by using Schrodinger software. Results: Among the synthesized analogues 12 and 13 show good antiproliferative activity with IC50 values 1and 1.3 µM respectively. Molecular docking suggests a remarkable binding pose of all the seventeen compounds. Compounds 12 and 13 were found to exhibit dock score of -4.10 kcal/mol and -4.38 kcal/mol respectively. Conclusion: Compounds 12 and 13 showed the highest activity followed by 1 and 5. ADME properties of all compounds were in the acceptable range. The active compounds can be taken for lead optimization and mechanistic interventions for their in vivo study in the future.

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Development of adamantane scaffold containing 1,3,4-thiadiazole derivatives: design, synthesis, anti-proliferative activity and molecular docking study targeting EGFR

Bioorganic Chemistry ◽

10.1016/j.bioorg.2021.104794 ◽

2021 ◽

pp. 104794

Author(s):

Mohammed M. S. Wassel ◽

Yousry A. Ammar ◽

Gameel A. M. Elhag Ali ◽

Amany Belal ◽

Ahmed B. M. Mehany ◽

...

Keyword(s):

Molecular Docking ◽

Proliferative Activity ◽

Docking Study ◽

Molecular Docking Study ◽

Design Synthesis ◽

Thiadiazole Derivatives

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Design, synthesis, biological evaluation and molecular docking study of novel thieno[3,2-d]pyrimidine derivatives as potent FAK inhibitors

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2019.112024 ◽

2020 ◽

Vol 188 ◽

pp. 112024 ◽

Cited By ~ 6

Author(s):

Ruifeng Wang ◽

Sijia Yu ◽

Xiangxin Zhao ◽

Yixuan Chen ◽

Bowen Yang ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Biological Evaluation ◽

Pyrimidine Derivatives ◽

Molecular Docking Study ◽

Design Synthesis

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ChemInform Abstract: Synthesis, Biological Evaluation and Molecular Docking Studies of Some Pyrimidine Derivatives.

ChemInform ◽

10.1002/chin.201352176 ◽

2013 ◽

Vol 44 (52) ◽

pp. no-no

Author(s):

Ahmed M. Fargualy ◽

Nargues S. Habib ◽

Khadiga A. Ismail ◽

Ahmed M. M. Hassan ◽

Marwa T. M. Sarg

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

Biological Evaluation ◽

Pyrimidine Derivatives ◽

Molecular Docking Studies

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Anti-Proliferative Activity of Piper trioicum Leaf Essential Oil Based on Phytoconstituent Analysis, Molecular Docking and In Silico ADMET Approaches

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207325666211222113239 ◽

2021 ◽

Vol 25 ◽

Author(s):

Sudipta Jena ◽

Asit Ray ◽

Ambika Sahoo ◽

Prabhat Kumar Das ◽

Pradeep Kumar Kamila ◽

...

Keyword(s):

Molecular Docking ◽

Chemical Composition ◽

Essential Oil ◽

Essential Oils ◽

Cell Lines ◽

In Silico ◽

Proliferative Activity ◽

In Silico Admet ◽

Leaf Essential Oil ◽

Ht 29

Background: The essential oils isolated from several medicinal plants are reported to have anticancer activities. Both the essential oil and extracts of many Piper species (Piperaceae) possess potential cytotoxic effect against cancer cell lines and are being used in traditional system of medicine for the treatment of cancer. There is a need to evaluate and validate the anticancer properties of essential oils extracted from other wild species of Piper. Objective: The current research was undertaken to determine the chemical composition and investigate the anti-proliferative activity of wild growing Piper trioicum leaf essential oil. The selected five major constituents were subjected to molecular docking to identify possible modes of binding against serine/threonine-protein kinase (MST3) protein Methods: The essential oil of leaf of P. trioicum was extracted by hydro distillation method and its chemical composition was carried out by GC-FID and GC-MS. The anti-proliferative activity of the essential oil was evaluated by MTT assay against normal (3T3-L1) and various cancer (HCT 116, HT-29, PC-3 and HepG2) cell lines. Molecular docking analysis was performed using AutoDock 4.2 software. The pharmacokinetic and pharmacodynamic properties of the major constituents were determined using absorption, distribution, metabolization, excretion and toxicity (ADMET) analysis. Results: The GC-MS analysis revealed the identification of 45 constituents with δ-cadinene (19.57%), germacrene-D (8.54%), β-caryophyllene (6.84%), 1-epi-cubenol (4.83%) and α-pinene (4.52%) were found to be predominant constituents in the leaf essential oil of P. trioicum. The highest cytotoxicity of essential oil was observed against HT-29 cells (IC50 value of 33.14 µg/ml). 1-epi-cubenol and δ-Cadinene exhibited low binding energy values of -6.25 and -5.92 kcal/mol, respectively. For prediction of in silico pharmacokinetic and druglike properties of the major compounds, ADMET prediction tool was also used, the results of which came within the ideal range. Conclusion: The present findings demonstrated that P. trioicum essential oil possesses significant anti-proliferative activity and could be effective against cancer treatment.

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Synthesis, characterization and molecular docking studies on some new N-substituted 2-phenylpyrido[2,3-d]pyrimidine derivatives

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00667 ◽

2021 ◽

pp. 3846-3854

Author(s):

Vivek B. Panchabhai ◽

Santosh R. Butle ◽

Parag G. Ingole

Keyword(s):

Crystal Structure ◽

Antibacterial Activity ◽

Molecular Docking ◽

Active Site ◽

Docking Studies ◽

Biotin Carboxylase ◽

Active Site Residues ◽

Pyrimidine Derivatives ◽

Molecular Docking Studies ◽

Novel Scaffold

We report a novel scaffold of N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives with potent antibacterial activity by targeting this biotin carboxylase enzyme. The series of eighteen N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives were synthesized, characterized and further molecular docking studied to determine the mode of binding and energy changes with the crystal structure of biotin carboxylase (PDB ID: 2V58) was employed as the receptor with compounds 6a-r as ligands. The results obtained from the simulation were obtained in the form of dock score; these values represent the minimum energies. Compounds 6d, 6l, 6n, 6o, 6r and 6i showed formation of hydrogen bonds with the active site residues and van Der Walls interactions with the biotin carboxylase enzyme in their molecular docking studies. This compound can be studied further and developed into a potential antibacterial lead molecule.

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Virtual Analysis of Condensed Pyrimidine Derivatives as COX II Inhibitors Potential Anti-inflammatory Agents

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00945 ◽

2021 ◽

pp. 5423-5426

Author(s):

S. A. Khedkar ◽

J. S. Patil ◽

P. M. Sabale

Keyword(s):

Molecular Docking ◽

Therapeutic Agents ◽

Vital Role ◽

Present Communication ◽

Pyrimidine Derivatives ◽

Protein Targets ◽

Docking Analysis ◽

Virtual Analysis ◽

Anti Inflammatory ◽

Important Enzyme

Drug design and development is an interactive process includes process like molecular docking which involves virtual analysis of the derivatives against the protein targets. COXS are the groups of enzymes which plays vital role in the human process. COX II is important enzyme involved in the inflammation and can act as potential target for development of the potent anti-inflammatory agents. Pyrimidine is one of the most utilized heterocyclic scaffolds for the development of therapeutic agents due to its role in the nucleic acid and proteins in the human body. The present communication deals with docking analysis of virtually designed 58 condensed pyrimidine derivatives as potential anti-inflammatory agents. The derivatives were designed and virtually screened via molecular docking against the COX-II crystal structure to identically the potential leads.

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