Design, synthesis, and anticancer evaluation of long-chain alkoxylated mono-carbonyl analogues of curcumin

Weng, Qiaoyou; Fu, Lili; Chen, Gaozhi; Jing, Hui; Shen, Jingjing; Feng, Jiaxuan; Shi, Dengjian; Cai, Yuepiao; Ji, Jiansong; Liang, Guang

doi:10.1016/j.ejmech.2015.08.036

Cited by 26 publications

(12 citation statements)

References 25 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the literature, monocarbonyl analogs of CUR based on non-heterocyclic and heterocyclic (piperidin-4-one and tropinone) scaffolds are also known [ 28 , 29 , 30 ] ( Scheme 2 ). In vitro tests have demonstrated the several anti-cancer activities of monocarbonyl analogs of CUR [ 31 , 32 , 33 , 34 ]. However, reports on monocarbonyl analogs of CUR, based on the granatanone scaffold, are elusive [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

“…One of the compounds formed during the thermal decomposition of CUR is decetocurcumin (DKC) ( Scheme 4 ), which is a monocarbonyl analog of CUR. A cell viability test proved that DKC induced the apoptosis of B78H1 murine melanoma cells [ 33 ]. Moreover, DKC protected cells against deposition of harmful β -amyloid and it reduced allergy induced by mast cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Monocarbonyl Analogs of Curcumin Based on the Pseudopelletierine Scaffold: Synthesis and Anti-Inflammatory Activity

Pawelski

Walewska

Ksiezak

et al. 2021

IJMS

View full text Add to dashboard Cite

Curcumin (CUR) is a natural compound that exhibits anti-inflammatory, anti-bacterial, and other biological properties. However, its application as an effective drug is problematic due to its poor oral bioavailability, solubility in water, and poor absorption from the gastrointestinal tract. The aim of this work is to synthesize monocarbonyl analogs of CUR based on the 9-methyl-9-azabicyclo[3.2.1]nonan-3-one (pseudopelletierine, granatanone) scaffold to improve its bioavailability. Granatane is a homologue of tropane, whose structure is present in numerous naturally occurring alkaloids, e.g., l-cocaine and l-scopolamine. In this study, ten new pseudopelletierine-derived monocarbonyl analogs of CUR were successfully synthesized and characterized by spectral methods and X-ray crystallography. Additionally, in vitro test of the cytotoxicity and anti-inflammatory properties of the synthesized compounds were performed.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Monocarbonyl Analogs of Curcumin Based on the Pseudopelletierine Scaffold: Synthesis and Anti-Inflammatory Activity

Pawelski

Walewska

Ksiezak

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Although previous studies suggest that the presence of the β-diketone moiety may be necessary for the biological activities of CUR, a number of studies from several independent groups demonstrated that certain CUR analogues containing a 5-carbon enone spacer without β-diketone either retained or increased the growth-suppressive activities of CUR against several cancer cells (16,17). Those studies indicate that certain mono-carbonyl analogues not only have enhanced stability and antitumor activities in vitro, but also have better pharmacokinetic profiles in vivo than CUR (18). One such compound, (1E,4E)-1,5-bis(2-bromophenyl) penta-1,4-dien-3-one (GL63) was synthesized as part of a series of novel CUR analogues (19).…”

Section: Introductionmentioning

confidence: 99%

A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma

et al. 2016

View full text Add to dashboard Cite

Abstract. Curcumin (CUR) has been demonstrated to protect against carcinogenesis and to prevent tumor development in cancer; however, the clinical application of CUR is limited by its instability and poor metabolic properties. The present study offers an strategy for a novel CUR analogue, (1E,4E)-1,5-bis(2-bromophenyl)penta-1,4-dien-3-one (GL63), to be used as a potential therapeutic agent for hepatocellular carcinoma (HCC) in vitro and in vivo. The current study demonstrated that GL63 exhibited more potent inhibition of proliferation of HCC cells than CUR. GL63 induced G0/G1 phase cell cycle arrest and apoptosis in SK-HEP-1 cells in a dose-dependent manner, and was more potent than CUR, according to the flow cytometry data. The present study demonstrated for the first time that the inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway by GL63 resulted in a protective effect against HCC cell growth. GL63 was more effective than CUR in regulating STAT3 downstream targets, which contributed to the suppression of cell proliferation and the induction of cell apoptosis. In addition, the effects of GL63 were tested in a model of N-nitrosodiethylamine (DEN)-induced HCC in Wistar rats. Although macroscopic and microscopic features suggested that both GL63 and CUR were effective in inhibiting DEN-induced hepatocarcinogenesis, GL63 exerted a stronger effect than CUR. Immunohistochemical analysis for proliferating cell nuclear antigen demonstrated significant differences among the DEN-bearing non-treated, DEN-bearing GL63-treated and DEN-bearing, CUR-treated groups (P=0.039). It was concluded that GL63 was a potent agent able to suppress the proliferation of HCC cells by inhibition of the JAK2/STAT3 signaling pathway, with more favorable pharmacological activity than CUR, and may be a more potent compound for the prevention of DEN-induced hepatocarcinogenesis in rats than CUR.

show abstract

“…5 Furthermore, owing to the frequent presence of a medium-chain 3-aminopropoxyl groups in several anticancer drugs, such as gefitinib, cediranib and SKI-6066 (Fig. 2), 6 we envisaged that chalcone derivatives with similar 3-aminopropoxyl groups might have excellent pharmacological activity, and in the present study we set out to design them via a molecular hybridisation strategy and then synthesise them.…”

mentioning

confidence: 99%

“…E) -1-(4-(3-(4-methylpiperazin-1-yl)propoxy)phenyl) -3-(3,4,5trimethoxyphenyl)prop-2-en-1-one (II-1): Yellow solid; m.p. 87-89 °C; yield 68%;1 H NMR (400 Hz, CDCl 3 ): δ 7.95 (d, J = 8.8 Hz, 2H), 7.64 (d, J = 15.6 Hz, 1H), 7.35 (d, J = 15.6 Hz, 1H),6.91 (d, J = 8.9 Hz, 2H), 6.79 (s, 2H), 4.03 (t, J = 6.3 Hz, 2H), 3.85 (s, 6H),3.83 (s, 3H), 2.89-2.23 (m, 10H), 2.22 (s, 3H), 2.00-1.86 (m, 2H); 13 C NMR (100 Hz, CDCl 3 ): δ 188.7, 162.9, 153.5, 144.1, 140.2, 131.0, 130.8, 130.6, 121.3, 114.3, 105.6, 66.5, 61.0, 56.2, 55.1, 53.2, 46.0, 26.6, 1.0; HRMS (ESI) calcd for C 26 H 34 N 2 NaO 5 [M + Na] + : 477.2369; found: 477.2365. ( E) -3-(4-chlorophenyl) -1-(4-(3-(pyrrolidin-1-yl) propoxy) phenyl)prop-2-en-1-one (II-2): Yellow solid; m.p.…”

mentioning

confidence: 99%

Design, Synthesis and Antiproliferative Evaluation of 3-Aminopropyloxy Derivatives of Chalcone

Zhang

Liu

et al. 2016

Journal of Chemical Research

View full text Add to dashboard Cite

A series of 3-aminopropyloxy derivatives of chalcone were synthesised and evaluated for their antiproliferative activity against liver, gastric and neuroendocrine cancer cell lines. Most of the synthesised compounds exhibited moderate to good activity against all three cancer cell lines, but in particular, a 3-(pyrrolidin-1-yl)propyloxy chalcone containing a 3,4,5-trimethoxyphenyl group showed the highest antiproliferative activity with an IC50 value of 2.74 μM against liver cancer cells.

show abstract

Design, synthesis, and anticancer evaluation of long-chain alkoxylated mono-carbonyl analogues of curcumin

Cited by 26 publications

References 25 publications

Monocarbonyl Analogs of Curcumin Based on the Pseudopelletierine Scaffold: Synthesis and Anti-Inflammatory Activity

Monocarbonyl Analogs of Curcumin Based on the Pseudopelletierine Scaffold: Synthesis and Anti-Inflammatory Activity

A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma

Design, Synthesis and Antiproliferative Evaluation of 3-Aminopropyloxy Derivatives of Chalcone

Contact Info

Product

Resources

About