In:
Archiv der Pharmazie, Wiley, Vol. 348, No. 10 ( 2015-10), p. 730-742
Abstract:
Tolmetin hydrazide and a novel series of tolmetin hydrazide–hydrazones 4a–l were synthesized in this study. The structures of the new compounds were determined by spectral (FT‐IR, 1 H NMR) methods. N ′‐[(2,6‐Dichlorophenyl)methylidene]‐2‐[1‐methyl‐5‐(4‐methylbenzoyl)‐1 H ‐pyrrol‐2‐yl]acetohydrazide ( 4g ) was evaluated in vitro using the MTT colorimetric method against the colon cancer cell lines HCT‐116 (ATCC, CCL‐247) and HT‐29 (ATCC, HTB‐38) to determine growth inhibition and cell viability at different doses. Compound 4g exhibited anti‐cancer activity with an IC 50 value of 76 μM against colon cancer line HT‐29 (ATCC, HTB‐38) and did not display cytotoxicity toward control NIH3T3 mouse embryonic fibroblast cells compared to tolmetin. In addition, this compound was evaluated for caspase‐3, caspase‐8, caspase‐9, and annexin‐V activation in the apoptotic pathway, which plays a key role in the treatment of cancer. We demonstrated that the anti‐cancer activity of this compound was due to the activation of caspase‐8 and caspase‐9 involved in the apoptotic pathway. In addition, in this study, we investigated the catalytical effect of COX on the HT‐29 cancer line, the apoptotic mechanism, and the moleculer binding of tolmetin and compound 4g on the COX enzyme active site.
Type of Medium:
Online Resource
ISSN:
0365-6233
,
1521-4184
DOI:
10.1002/ardp.v348.10
DOI:
10.1002/ardp.201500178
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
1496815-0
SSG:
15,3
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