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Synthesis, evaluation of thymidine phosphorylase and angiogenic inhibitory potential of ciprofloxacin analogues: Repositioning of ciprofloxacin from antibiotic to future anticancer drugs.
- Source :
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Bioorganic chemistry [Bioorg Chem] 2020 Jul; Vol. 100, pp. 103876. Date of Electronic Publication: 2020 Apr 22. - Publication Year :
- 2020
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Abstract
- Over expression of thymidine phosphorylase (TP) in various human tumors compared to normal healthy tissue is associated with progression of cancer and proliferation. The 2-deoxy-d-ribose is the final product of thymidine phosphorylase (TP) catalyzed reaction. Both TP and 2-deoxy-d-ribose are known to promote unwanted angiogenesis in cancerous cells. Discovery of potent inhibitors of thymidine phosphorylase (TP) can offer appropriate approach in cancer treatment. A series of ciprofloxacin 2, 3a-3c, 4a-4d, 5a-5b, 6 and 7 has been synthesized and characterized using spectroscopic techniques. Afterwards, inhibitory potential of synthesized ciprofloxacin 2, 3a-3c, 4a-4d, 5a-5b, 6 and 7 against thymidine phosphorylase enzyme was assessed. Out of these twelve analogs of ciprofloxacin nine analogues 3a-3c, 4a-4c, 5a-5b and 6 showed good inhibitory activity against thymidine phosphorylase. Inhibitory activity as presented by their IC <subscript>50</subscript> values was found in the range of 39.71 ± 1.13 to 161.89 ± 0.95 μM. The 7-deazaxanthine was used as a standard inhibitor with IC <subscript>50</subscript>  = 37.82 ± 0.93 μM. Furthermore, the chick chorionic allantoic membrane (CAM) assay was used to investigate anti-angiogenic activity of the most active ciprofloxacin-based inhibitor 3b. To enlighten the important binding interactions of ciprofloxacin derivatives with target enzyme, the structure activity relationship and molecular docking studies of chosen ciprofloxacin analogues was discussed. Docking studies revealed key π-π stacking, π-cation and hydrogen bonding interactions of ciprofloxacin analogues with active site residues of thymidine phosphorylase enzyme.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Angiogenesis Inhibitors chemical synthesis
Animals
Anti-Bacterial Agents chemical synthesis
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Chick Embryo
Ciprofloxacin chemical synthesis
Drug Repositioning
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors chemistry
Enzyme Inhibitors pharmacology
Humans
Molecular Docking Simulation
Thymidine Phosphorylase metabolism
Angiogenesis Inhibitors chemistry
Angiogenesis Inhibitors pharmacology
Anti-Bacterial Agents chemistry
Anti-Bacterial Agents pharmacology
Ciprofloxacin analogs & derivatives
Ciprofloxacin pharmacology
Thymidine Phosphorylase antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 100
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 32388426
- Full Text :
- https://doi.org/10.1016/j.bioorg.2020.103876