1. Academic Validation
  2. Design, Synthesis, and Anticancer Evaluation of Novel Tetracaine Hydrazide-Hydrazones

Design, Synthesis, and Anticancer Evaluation of Novel Tetracaine Hydrazide-Hydrazones

  • ACS Omega. 2023 Feb 28;8(10):9198-9211. doi: 10.1021/acsomega.2c07192.
M İhsan Han 1 Nalan İmamoğlu 2
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri 38039, Turkey.
  • 2 Department of Basic Sciences, Faculty of Pharmacy, Erciyes University, Kayseri 38039, Turkey.
Abstract

Tetracaine is an ester derivative used as a local anesthetic molecule. In this study, a series of novel Tetracaine derivatives bearing hydrazide-hydrazone moiety were designed, synthesized, and evaluated for Anticancer activity. The structures of these compounds were characterized by spectral (1H NMR,13C NMR, FT-IR, and HRMS analyses) methods. All synthesized compounds were screened for Anticancer activity against two different human Cancer cell lines (Colo-205 and HepG2). Among the synthesized molecules, compounds 2f and 2m showed the most potent Anticancer activity against the Colo-205 cell line (IC50 = 50.0 and 20.5 μM, respectively). Compounds 2k, 2p, and 2s demonstrated the best Anticancer activity against the HepG2 cell line (IC50 = 30.5, 35.9, and 20.8 μM, respectively). mRNA transcription levels of Bax and Caspase-3 genes were determined by real-time polymerase chain reaction (qRT-PCR) analysis of both Colo-205 and HepG2 cell lines. Doxorubicin was used as a positive sensitivity reference standard. qRT-PCR analysis showed that there was a time-dependent rise in the expression levels of Bax and Caspase 3 on Apoptosis. Inhibition of apoptotic proteins PI3K, Akt, PTEN, pPTEN, FoXO1, FoXO3a, TXNIP, and p27 was investigated in Colo-205 and HepG2 cells treated with compounds 2f, 2m, 2k, 2p, and 2s by using Western blotting.

Figures
Products