New histone deacetylase inhibitors and anticancer agents from Curcuma longa

Kumboonma, Pakit; Senawong, Thanaset; Saenglee, Somprasong; Senawong, Gulsiri; Somsakeesit, La-or; Yenjai, Chavi; Phaosiri, Chanokbhorn

doi:10.1007/s00044-019-02414-5

Cited by 11 publications

(16 citation statements)

References 45 publications

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“…In addition, NEP activity has been found to be reduced in the presence of Aβ-generated reactive oxygen species (ROS) [46]. In that respect, the work of Zheng et al reported superior anti-oxidant activity for monocarbonyl curcumin derivatives, including some of our tested compounds [47]. This may contribute, at least partially, to the NEP activity enhancement observed herein.…”

Section: Nep Aβ-degrading Activity In Cells and Inhibition Studiessupporting

confidence: 54%

Synthesis and Biological Evaluation of Hydroxylated Monocarbonyl Curcumin Derivatives as Potential Inducers of Neprilysin Activity

Matiadis

Chen

et al. 2021

Biomedicines

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Background: Alzheimer’s disease (AD) involves impairment of Aβ clearance. Neprilysin (NEP) is the most efficient Aβ peptidase. Enhancement of the activity or expression of NEP may provide a prominent therapeutic strategy against AD. Aims: Ten hydroxylated monocarbonyl curcumin derivatives were designed, synthesized and evaluated for their NEP upregulating potential using sensitive fluorescence-based Aβ digestion and inhibition assays. Results: Compound 4 was the most active one, resulting in a 50% increase in Aβ cleavage activity. Cyclohexanone-bearing derivatives exhibited higher activity enhancement compared to their acetone counterparts. Inhibition experiments with the NEP-specific inhibitor thiorphan resulted in dramatic cleavage reduction. Conclusion: The increased Aβ cleavage activity and the ease of synthesis of 4 renders it an extremely attractive lead compound.

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Section: Nep Aβ-degrading Activity In Cells and Inhibition Studiessupporting

confidence: 54%

Synthesis and Biological Evaluation of Hydroxylated Monocarbonyl Curcumin Derivatives as Potential Inducers of Neprilysin Activity

Matiadis

Chen

et al. 2021

Biomedicines

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“…In the present study, we determined the anti-cancer activity of the curcumin derivative CU17 and explored its underlying antitumor mechanisms against human lung cancer cells. CU17 used in this study was successfully synthesized from CU according to previously described methods [21], and data demonstrating successful synthesis/purity check are provided in the supplementary materials. The structure and function of histone proteins are altered by an imbalance between histone acetyltransferases (HATs) and histone deacetylases (HDACs), which affects cancer cell processes [26].…”

Section: Discussionmentioning

confidence: 99%

“…However, CU exhibited a more cytotoxic effect against non-cancer Vero cells. The amino derivatives of CU, such as CU16, CU17, CU18 and CU19, were synthesized by chemical modification of CU [21]. They displayed a lower physiochemical instability but stronger pharmacological activities than the CU analog.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, several amino derivatives of curcumin (CU16, CU17, CU18 and CU19) with lower physiochemical instability but stronger pharmacological activities than curcumin have been synthesized [21]. In this present research, the curcumin derivative CU17 with 2-aminothiophenol (Figure 1) was chosen for further studies on its HDAC inhibitory and anti-cancer activities against the NSCLC cell line because it presented the least toxicity to non-cancer cells (Vero cells) and great efficiency of anti-proliferative activity against several cancer cell lines [21]. At the screening concentration of 100 µM, CU17 had greater HDAC inhibition (73%) than curcumin (62%) [21].…”

Section: Introductionmentioning

confidence: 99%

“…In this present research, the curcumin derivative CU17 with 2-aminothiophenol (Figure 1) was chosen for further studies on its HDAC inhibitory and anti-cancer activities against the NSCLC cell line because it presented the least toxicity to non-cancer cells (Vero cells) and great efficiency of anti-proliferative activity against several cancer cell lines [21]. At the screening concentration of 100 µM, CU17 had greater HDAC inhibition (73%) than curcumin (62%) [21]. However, its anti-cancer activity against lung cancer cells has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

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HDAC Inhibitory and Anti-Cancer Activities of Curcumin and Curcumin Derivative CU17 against Human Lung Cancer A549 Cells

et al. 2022

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Previous research reported that the curcumin derivative (CU17) inhibited several cancer cell growths in vitro. However, its anticancer potential against human lung cancer cells (A549 cell lines) has not yet been evaluated. The purpose of this research was to examine the HDAC inhibitory and anti-cancer activities of CU17 compared to curcumin (CU) in A549 cells. An in vitro study showed that CU17 had greater HDAC inhibitory activity than CU. CU17 inhibited HDAC activity in a dose dependent manner with the half-maximal inhibitory concentration (IC50) value of 0.30 ± 0.086 µg/mL against HDAC enzymes from HeLa nuclear extract. In addition, CU17 could bind at the active pockets of both human class I HDACs (HDAC1, 2, 3, and 8) and class II HDACs (HDAC4, 6, and 7) demonstrated by molecular docking studies, and caused hyperacetylation of histone H3 (Ac-H3) in A549 cells shown by Western blot analysis. MTT assay indicated that both CU and CU17 suppressed A549 cell growth in a dose- and time-dependent manner. Besides, CU and CU17 induced G2/M phase cell cycle arrest and p53-independent apoptosis in A549 cells. Both CU and CU17 down-regulated the expression of p53, p21, Bcl-2, and pERK1/2, but up-regulated Bax expression in this cell line. Although CU17 inhibited the growth of lung cancer cells less effectively than CU, it showed less toxicity than CU for non-cancer cells. Accordingly, CU17 is a promising agent for lung cancer treatment. Additionally, CU17 synergized the antiproliferative activity of Gem in A549 cells, indicating the possibility of employing CU17 as an adjuvant treatment to enhance the chemotherapeutic effect of Gem in lung cancer.

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Investigation of in vitro HDAC 1 inhibitory activity of Curcuma longa L. extracts, isolated fractions and curcumin

Koyu,

Istanbullu,

Turunc Ozoglu

et al. 2023

Eur Food Res Technol

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New histone deacetylase inhibitors and anticancer agents from Curcuma longa

Cited by 11 publications

References 45 publications

Synthesis and Biological Evaluation of Hydroxylated Monocarbonyl Curcumin Derivatives as Potential Inducers of Neprilysin Activity

Synthesis and Biological Evaluation of Hydroxylated Monocarbonyl Curcumin Derivatives as Potential Inducers of Neprilysin Activity

HDAC Inhibitory and Anti-Cancer Activities of Curcumin and Curcumin Derivative CU17 against Human Lung Cancer A549 Cells

Investigation of in vitro HDAC 1 inhibitory activity of Curcuma longa L. extracts, isolated fractions and curcumin

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