Development of 1,3-diynyl derivatives of noscapine as potent tubulin binding anticancer agents for the management of breast cancer

The investigational anticancer agents laulimalide and peloruside are known to exert an antimitotic effect on cells by binding to β-tubulin. The binding affinities of derivatives of laulimalide and peloruside to all known isoforms of human β-tubulin were calculated using molecular mechanical, molecular dynamical, and quantum mechanical methods. Several of the derivatives are predicted to have improved β-tubulin binding affinities compared to the parent structures. These results can form the starting point for developing laulimalide or peloruside derivatives with greater specificity for the particular β-tubulin isoforms, which are overexpressed in certain tumours.

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Synthesis, In-vitro and Docking Analysis of C-3 substituted Coumarin Analogues as Anticancer Agents C-3 Substituted Coumarins as Anticancer Agents

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200120114641 ◽

2020 ◽

Vol 16 ◽

Author(s):

Anuradha Thakur ◽

Kamalpreet Kaur ◽

Praveen Sharma ◽

Ramit Singla ◽

Sandeep Singh ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Docking ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Anticancer Agents ◽

Proliferative Activity ◽

Binding Interaction ◽

Diverse Range ◽

Mcf 7 ◽

Substituted Coumarins

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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Hybridized Quinoline Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and Molecular Docking

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666181112121058 ◽

2019 ◽

Vol 19 (4) ◽

pp. 439-452 ◽

Cited By ~ 3

Author(s):

Mohamed R. Selim ◽

Medhat A. Zahran ◽

Amany Belal ◽

Moustafa S. Abusaif ◽

Said A. Shedid ◽

...

Keyword(s):

Cell Cycle ◽

Anticancer Agents ◽

Caspase 3 ◽

Biological Evaluation ◽

Tubulin Polymerization ◽

Design Synthesis ◽

Chemical Structures ◽

M Phase ◽

Induced Apoptosis ◽

Derivatives Of

Objective: Conjugating quinolones with different bioactive pharmacophores to obtain potent anticancer active agents. Methods: Fused pyrazolopyrimidoquinolines 3a-d, Schiff bases 5, 6a-e, two hybridized systems: pyrazolochromenquinoline 7 and pyrazolothiazolidinquinoline 8, different substituted thiazoloquinolines 13-15 and thiazolo[3,2-a]pyridine derivatives 16a-c were synthesized. Their chemical structures were characterized through spectral and elemental analysis, cytotoxic activity on five cancer cell lines, caspase-3 activation, tubulin polymerization inhibition and cell cycle analysis were evaluated. Results: Four compounds 3b, 3d, 8 and 13 showed potent activity than doxorubicin on HCT116 and three compounds 3b, 3d and 8 on HEPG2. These promising derivatives showed increase in the level of caspase-3. The trifloromethylphenyl derivatives of pyrazolopyrimidoquinolines 3b and 3d showed considerable tubulin polymerization inhibitory activity. Both compounds arrested cell cycle at G2/M phase and induced apoptosis. Conclusion: Compounds 3b and 3d can be considered as promising anticancer active agents with 70% of colchicine activity on tubulin polymerization inhibition and represent hopeful leads that deserve further investigation and optimization.

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Three Amino Acid Derivatives of Valproic Acid: Design, Synthesis, Theoretical and Experimental Evaluation as Anticancer Agents

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520614666140127113218 ◽

2014 ◽

Vol 14 (7) ◽

pp. 984-993 ◽

Cited By ~ 3

Author(s):

Gabriela Luna-Palencia ◽

Federico Martinez-Ramos ◽

Ismael Vasquez-Moctezuma ◽

Manuel Fragoso-Vazquez ◽

Jessica Mendieta-Wejebe ◽

...

Keyword(s):

Valproic Acid ◽

Amino Acid ◽

Anticancer Agents ◽

Experimental Evaluation ◽

Amino Acid Derivatives ◽

Design Synthesis ◽

Derivatives Of

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Design, Synthesis, In Vitro and In Silico Studies of Some Novel Triazoles as Anticancer Agents for Breast Cancer

Journal of Molecular Structure ◽

10.1016/j.molstruc.2021.131198 ◽

2021 ◽

pp. 131198

Author(s):

Derya Osmaniye ◽

Begum Nurpelin Saglik ◽

Serkan Levent ◽

Sinem Ilgın ◽

Yusuf Ozkay ◽

...

Keyword(s):

Breast Cancer ◽

Anticancer Agents ◽

In Silico ◽

Design Synthesis ◽

In Silico Studies

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Synthetis of Potential Anticancer Agents. XVI. S-Substituted Derivatives of 6-Mercaptopurine1a

Journal of the American Chemical Society ◽

10.1021/ja01556a026 ◽

1958 ◽

Vol 80 (23) ◽

pp. 6265-6271 ◽

Cited By ~ 41

Author(s):

Thomas P. Johnston ◽

Lee B. Holum ◽

John A. Montgomery

Keyword(s):

Anticancer Agents ◽

Derivatives Of

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Synthesis, Characterization, and Biological Studies of a Piperidinyl Appended Dipicolylamine Ligand and Its Rhenium Tricarbonyl Complex as Potential Therapeutic Agents for Human Breast Cancer

Bioinorganic Chemistry and Applications ◽

10.1155/2016/2675937 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Amali Subasinghe ◽

Inoka C. Perera ◽

Svetlana Pakhomova ◽

Theshini Perera

Keyword(s):

Breast Cancer ◽

Anticancer Agents ◽

Human Breast Cancer ◽

Human Breast ◽

Tricarbonyl Complex ◽

Nmr Spectrum ◽

H Nmr ◽

Biological Studies ◽

Visible Spectra ◽

Uv Visible

A novel ligand bearing a central piperidinyl sulfonamide group, N(SO2pip)dpa, and its corresponding Re tricarbonyl complex, [Re(CO)3(N(SO2pip)dpa)]+, have been synthesized in good yield. The methylene CH2signal seen as a singlet (4.54 ppm) in a1H NMR spectrum of the ligand in DMSO-d6appears as two doublets (5.39, 5.01 ppm) in a spectrum of the [Re(CO)3(N(SO2pip)dpa)]+complex and confirms the presence of magnetically nonequivalent protons upon coordination to Re. Structural results revealed that the Re–N bond lengths fall within the normal range establishing coordination of ligand to metal. The presence of intraligandπ→π⁎andn→π⁎transitions is indicated by the absorption peaks around 200–250 nm in UV-visible spectra. Absorption peaks in UV-visible spectra around 300 nm for metal complexes were identified as MLCT transitions. The S–N stretch observed as a strong peak at 923 cm−1for N(SO2pip)dpa appeared at a shorter frequency, at 830 cm−1in an FTIR spectrum of the [Re(CO)3(N(SO2pip)dpa)]+. The intense fluorescence displayed by the N(SO2pip)dpa ligand has quenched upon coordination to Re. Relatively low IC50values given by human breast cancer cells, MCF-7, (N(SO2pip)dpa = 139 μM, [Re(CO)3(N(SO2pip)dpa)]+= 360 μM) indicate that N(SO2pip)dpa and [Re(CO)3(N(SO2pip)dpa)]+are promising novel compounds that can be further investigated on their usage as potential anticancer agents.

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