Design, Synthesis, and Evaluation of a New Series of Hydrazones as Small-Molecule Akt Inhibitors for NSCLC Therapy

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Erdönmez B., Altıntop M. D., Akalın Çiftçi G., Özdemir A., Ece A.

ACS OMEGA, cilt.8, sa.22, ss.20056-20065, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 8 Sayı: 22
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1021/acsomega.3c02331
  • Dergi Adı: ACS OMEGA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Directory of Open Access Journals
  • Sayfa Sayıları: ss.20056-20065
  • Anadolu Üniversitesi Adresli: Evet

Özet

In an endeavor to identify small molecules for the managementofnon-small-cell lung carcinoma, 10 new hydrazone derivatives (3a-j) were synthesized. MTT test was conducted to examinetheir cytotoxic activities against human lung adenocarcinoma (A549)and mouse embryonic fibroblast (L929) cells. Compounds 3a, 3e, 3g, and 3i were determinedas selective antitumor agents on A549 cell line. Further studies wereconducted to figure out their mode of action. Compounds 3a and 3g markedly induced apoptosis in A549 cells. However,both compounds did not show any significant inhibitory effect on Akt.On the other hand, in vitro experiments suggest thatcompounds 3e and 3i are potential anti-NSCLCagents acting through Akt inhibition. Furthermore, molecular dockingstudies revealed a unique binding mode for compound 3i (the strongest Akt inhibitor in this series), which interacts withboth hinge region and acidic pocket of Akt2. However, it is understoodthat compounds 3a and 3g exert their cytotoxicand apoptotic effects on A549 cells via differentpathway(s).