Evaluation of N-aryl-β-alanine derivatives as anticancer agents in triple-negative breast cancer and glioblastoma in vitro models

• Published in: Bioorganic chemistry 2021-10, Vol.115, p.105214-105214, Article 105214
• Main Authors: Žukauskas, Mindaugas, Grybaitė, Birutė, Jonutė, Paulina, Vaickelionienė, Rita, Gibieža, Paulius, Vaickelionis, Giedrius, Dragūnaitė, Bertina, Anusevičius, Kazimieras, Mickevičius, Vytautas, Petrikaitė, Vilma
• Format: Article
• Language: English
• Subjects: Alanine - analogs & derivatives; Alanine - chemistry; Alanine - pharmacology; Anticancer activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Azoles; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Glioblastoma - drug therapy; Glioblastoma - metabolism; Glioblastoma - pathology; Humans; Hydrazones; Molecular Structure; Pyrrolidinones; Structure-Activity Relationship; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; β-Amino acids
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.105214

[Display omitted] •β-amino acids derivatives bearing hydrazone and azole moieties was synthesized.•Promising compounds against cancer cell lines contain 4-BrPh or 4-ClPh moieties.•Two selected drug candidates showed migrastatic effect on MDA-MB-231 cell line. Synthesis of β-amino acid derivatives containing hydrazone and azole moieties is described. For this purpose, the appropriate hydrazide was treated with aromatic aldehydes, ketones and phenyl iso(thio)cyanates to obtain the desired outcome. The synthesized target compounds were evaluated for their anticancer properties. The assay displayed 3,3′-((2,6-diethylphenyl)azanediyl)bis(N′-(benzylidene)propanehydrazide) to possess the convincing anticancer effect against triple-negative breast cancer cells in vitro. To further study the anticancer properties of compounds containing a hydrazone moiety in breast cancer, series of previously and newly prepared dihydrazones were investigated. It was determined that derivatives with the bis(N′-(4-bromobenzylidene) fragment in the structure are exclusively cytotoxic to cancer cells. The most active compounds against both cell lines were those containing electron withdrawing 4-BrPh or 4-ClPh moieties, together with either chlorine, bromine or iodine groups in para position of phenyl ring. Selected two representative compounds showed migrastatic activity in MDA-MB-231 cell line, where both of them reduced the growth of breast cancer and glioblastoma cell 3D cultures and inhibited cell colony formation. 2009 Elsevier Ltd. All rights reserved.