Novel imidazo[2,1-b]thiazole-based anticancer agents as potential focal adhesion kinase inhibitors: Synthesis, in silico and in vitro evaluation

Basoglu F., Ulusoy-Guzeldemirci N., AKALIN ÇİFTÇİ G., ÇETİNKAYA S., Ece A.

CHEMICAL BIOLOGY & DRUG DESIGN, cilt.98, sa.2, ss.270-282, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 98 Sayı: 2
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1111/cbdd.13896
  • Dergi Adı: CHEMICAL BIOLOGY & DRUG DESIGN
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.270-282
  • Anahtar Kelimeler: focal adhesion kinase, Imidazo[2, 1-b]thiazole, molecular docking, 4-THIAZOLIDINONE DERIVATIVES, ACCURATE DOCKING, CANCER, FAK, DESIGN, APOPTOSIS, PATHWAYS, BEARING, PROTEIN, TARGET
  • İstanbul Üniversitesi Adresli: Evet

Özet

The purpose of this study was to synthesize imidazo[2,1-b]thiazole derivatives, characterize them with spectroscopical techniques and investigate for cytotoxic and apoptotic effects on glioma C6 cancer cell line. The in vitro anticancer activities were also investigated against focal adhesion kinase. Most of the compounds, particularly the derivatives carrying 3-oxo-1-tiya-4-azaspiro[4.5]decane moiety, exhibited higher or comparable activities in comparison with the reference drug, cisplatin. Compounds with methyl, propyl, phenyl moieties at the eighth and second position of the spirothiazolidinone ring showed high FAK inhibitory activities. In addition, molecular docking studies shed light on the binding modes of the synthesized compounds. The critical interactions with amino acid residues located in the active site were revealed. The results obtained from both biological assay data and computational results might provide insight into developing new inhibitors against focal adhesion kinase.