Synthesis, characterization and anticancer activity of novel hydrazide-hydrazones derived from ethyl paraben

Abstract

Parabens, which are hydroxybenzoic acid esters, are particularly used as protective against mold and fungus. Ethyl paraben is a compound open to modification for the synthesis of new molecules due to the ester group in its structure. In this study, ethyl paraben was used as a starting material. A new series of novel hydrazide-hydrazones from derived ethyl paraben were synthesized and characterized by spectroscopic techniques such as NMR, FT-IR besides elemental analysis. In order to determine the anticancer activity of the aimed ethyl paraben hydrazidehydrazones we evaluated their cytotoxic activity on liver cancer cell line liver hepatocellular carcinoma (HepG2). Herein we described several 4-hydroxy-N'-[substituted methylidene] benzohydrazides (3a-j) as anticancer agents. We designed, synthesized and characterized the series of novel hydrazide-hydrazones from ethyl paraben. All of the compounds evaluated for anticancer activity by using MTT assay for 24 and 48 h. mRNA transcription levels of Bax, Bcl-2 and caspase-3 genes were determined by realtime polymerase chain reaction (qRT-PCR) analysis. Compounds 3i and 3j showed anticancer activity with 42.4 and 37.4 µM IC50 values, respectively. Doxorubicin was used as a positive sensitivity reference standard. qRTPCR analysis approved that there was a timedependent rise in the expression levels of Bax, Bcl-2 and Caspase 3 on apoptosis. The activities of the synthesized compounds changed depending on the dose and time of treatment and some of the molecules started to show activity within 48 hours.

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

“…Compounds 2a–t are original molecules. All synthesized molecules were characterized by their 1 H NMR, 13 C NMR, FT-IR, and HR-MS spectroscopic data. − …”

“…Cells were incubated in a sterile carbon dioxide incubator for 24 h. After 24 h, the medium was replaced with fresh medium. Test substances that are thought to affect cell viability were added to the culture medium at various concentrations of compounds ( 2a–t ) (12.5, 25, 50, 100, 200, and 400 μM), and the cells were incubated for 24 and 48 h. At the end of the incubation periods, the medium containing the substances was discarded and 10 μL MTT reagent in 100 μL medium was added to each well, and plates were allowed to incubate for 2 h. Formazan crystals formed as a result of incubation in viable cells were dissolved in 100 μL DMSO and absorbance was detected in a microplate reader at a wavelength of 570 nm …”

“…Pre-incubation at 95 °C for 10 min, 45 repetitions at 95 °C for 10 s, 60 °C for 30 s, 72 °C for a 1 s annealing cycle, and 40 °C for 30 s of cooling were recorded on the real-time PCR instrument. The Ct cycle was used to determine the expression level and control and 3i- and 3j-treated cells …”

“…13−27 Han et al synthesized novel hydrazide-hydrazone molecules and controlled the anticancer activity on the HepG2 cell line. 22 Anticancer activity studies of hydrazide-hydrazone molecules have been observed in many studies, and it has been determined that hydrazide-hydrazone molecules show activity against Colo-205 and HegG2 cell lines. 28−33 An azomethine (−NHN�CH−) proton becomes on hydrazide-hydrazones after the synthesis.…”

Synthesis and anticancer activity against prostate cancer of hydrazide-hydrazones derived from etodolac

“…In recent years, screening studies on anticancer effects on new compounds containing hydrazidehydrazone have gained importance in order to accelerate the development of new more effective, less toxic chemotherapeutic agents [11][12][13][14][15][16][17][18]. Especially in this period when COX-2 enzyme is an important molecular targeting for anticancer therapies, etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano [3,4-b]indole-1-yl)acetic acid) has been reported to have anticancer activity against various prostate cancers; Compounds in the structure of hydrazone, which have also been reported in the literature, have been synthesized using etodolac active substance.…”