53631-76-8Relevant academic research and scientific papers
Synthesis and evaluation of novel benzotropolones as Atg4B inhibiting autophagy blockers
Tanc, Muhammet,Cleenewerck, Matthias,Kurdi, Ammar,Roelandt, Ria,Declercq, Wim,De Meyer, Guido,Augustyns, Koen,Martinet, Wim,Van der Veken, Pieter
, p. 163 - 168 (2019)
Autophagy is an intracellular degradation/recycling pathway that provides nutrients and building blocks to cellular metabolism and keeps the cytoplasm clear of obsolete proteins and organelles. During recent years, dysregulated autophagy activity has been reported to be a characteristic of many different disease types, including cancer and neurodegenerative disorders. This has created a strong case for development of autophagy modulating compounds as potential treatments for these diseases. Inhibitors of autophagy have been proposed as a therapeutic intervention in, e.g., advanced cancer, and inhibiting the cysteine protease Atg4B has been put forward as a main strategy to block autophagy. We recently identified and demonstrated -both in vitro and in vivo - that compounds with a benzotropolone basic structure targeting Atg4B, can significantly slow down tumor growth and potentiate the effect of classical chemotherapy. In this study we report the synthesis and inhibition profile of new benzotropolone derivatives with additional structural modifications at 6 different positions. To obtain a solid inhibition profile, all compounds were evaluated on three levels, including two cell-based assays to confirm autophagy and intracellular Atg4B inhibition and an SDS-PAGE-based experiment to assess in vitro Atg4B affinity. Several molecules with a promising profile were identified.
Synthesis and anticancer effect of 3,4,5-n-alkyl-benzamides on colon carcinoma HCT- 116 cells
Chan, Jilly Octaria Tagore,Arsianti, Ade,Marcelia, Maurin,Wijoyo, Stevano Julio,Fadilah, Fadilah,Putrianingsih, Rista,Azizah, Norma Nur,Tanimoto, Hiroki,Kakiuchi, Kiyomi
, p. 1362 - 1367 (2018/07/23)
The natural phenolic gallic acid has demonstrated a significant inhibition of cell proliferation in a series of cancer cell lines, as well as induced apoptosis in HCT-116 colon cancer cells. This research aims to synthesize six compounds of 3,4,5-trihydroxy-N-alkyl-benzamide derivatives of gallic acid, and investigate its anticancer effect on colon carcinoma HCT-116 cells.Six compounds of 3,4,5-trihydroxy-N-alkyl-benzamide, namely 3,4,5-trihydroxy-N-methyl-benzamide (2); 3,4,5-trihydroxy-N-ethyl-benzamide (3); 3,4,5-trihydroxy-N-butyl-benzamide (4); 3,4,5-trihydroxy-N-sec-butyl-benzamide (5); 3,4,5-trihydroxy-N-tert-butyl-benzamide (6) and 3,4,5-trihydroxy-N-hexyl-benzamide (7), have been successfully synthesized by amidation of carboxyl group of gallic acid with six corresponding alkylamines, respectively. Furthermore, anticancer effect of these six synthesized derivatives on colon HCT-116 cells were examined by MTT assay. Data were analyzed by linear regression method to generate IC50 value. The results will be compared with gallic acid as an original compound and doxorubicine as a positive control.Amidation of gallic acid with six corresponding alkylamines gave desired -N-methyl-, -N-ethyl-, -N-butyl-, -N-sec-butyl-, -N-ters-butyl-, and –N-hexyl benzamide with yield ranging from 18% to 84%. Compared to gallic acid (IC50: 0.05 μM) and doxorubicine (IC50: 0.001 μM), all these six synthesized derivatives showed a lower anticancer effect on colon HCT-116 cells. The strongest anticancer and inhibitory effect on HCT-116 cells has shown by 3,4,5-trihydroxy-N-hexyl benzamide (7) with IC50 value of 0.07 μM. Our results suggested that 3,4,5-trihydroxy-N-hexyl benzamide (7) is a potential to be developed as a promising anti-colon cancer agent.
