Repository of Research and Investigative Information

Repository of Research and Investigative Information

Baqiyatallah University of Medical Sciences

Synthesis, In Silico and In Vitro Cytostatic Activity of New Lipophilic Derivatives of Hydroxyurea

(2018) Synthesis, In Silico and In Vitro Cytostatic Activity of New Lipophilic Derivatives of Hydroxyurea. Recent Patents on Anti-Cancer Drug Discovery. pp. 378-385. ISSN 1574-8928

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Abstract

Background: Hydroxyurea (HU) is used to treat cancer. HU has a short half-life due to its small molecular weight and high polarity, therefore a high dosage of the drug should be used which introduces side effects and more rapid development of resistance. Objective: The objective of the current study is to design new lipophilic analogues of hydroxyurea with higher stability and better cell penetration. The designed compounds were synthesized and then evaluated in terms of their cytostatic activities against two human cell lines. Methods: The synthesis of designed ligands was achieved via two-step procedure. Detail of the synthesis and chemical characterization of the analogs are described. The cytotoxic activity of the designed ligands was evaluated in vitro against two different cancer cell lines at 24 and 48h using MTT test. Results: Based on the IC50 values, all the designed and prepared compounds were more potent than hydroxyurea at 24 and 48h on both cell lines that the cytostatic activity at 48h was more than 24h. Drug-receptor interactions study indicated compound 7 as the most potent ligand, tightly bonded to surrounding amino acids in the active site of receptor via two strong hydrogen bonds and some hydrophobic interactions. Conclusion: Compound 7 with the suitable volume, log p and shape is the most active ligand against both cell lines. It is concluded or suggested that the size, shape and hydrophobic character of substituents strongly affect the pharmacodynamics and pharmacokinetics of these type of ligands.

Item Type: Article
Keywords: Hella cells hydroxyurea lipophilicity MTT panc cells ribonucleotide reductase ribonucleotide reductase schiff-bases mechanism Oncology Pharmacology & Pharmacy
Divisions:
Page Range: pp. 378-385
Journal or Publication Title: Recent Patents on Anti-Cancer Drug Discovery
Journal Index: ISI
Volume: 13
Number: 3
Identification Number: https://doi.org/10.2174/1574892813666180517102255
ISSN: 1574-8928
Depositing User: مهندس مهدی شریفی
URI: http://eprints.bmsu.ac.ir/id/eprint/4009

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