Synthesis and anticancer activity of a novel series of 9-O-substituted berberine derivatives: A lipophilic substitute role

Lo, Chih-Yu; Hsu, Lin-Chen; Chen, Min-Shin; Lin, Yijing; Chen, Lih Geeng; Kuo, Cheng‐Deng; Wu, Jin‐Yi

doi:10.1016/j.bmcl.2012.10.098

Cited by 59 publications

(27 citation statements)

References 24 publications

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“…Within the frame of an active search for compounds with cytotoxic effect on cancer cells, berberine (BBR) has been described as a promising drug; thus, new 9-O-derivatives [32] and 13-substituted BBR derivatives [33, 34] were designed and synthesized. The present work aimed to evaluate the biological effects of BBR and three derivatives (NAX012, NAX014, and NAX018) characterized by aromatic moieties bonded to the 13-position of BBR through a linker of variable length.…”

Section: Resultsmentioning

confidence: 99%

Multiple Effects of Berberine Derivatives on Colon Cancer Cells

Ortiz

Tillhon

Parks

et al. 2014

BioMed Research International

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The pharmacological use of the plant alkaloid berberine is based on its antibacterial and anti-inflammatory properties; recently, anticancer activity has been attributed to this compound. To exploit this interesting feature, we synthesized three berberine derivatives, namely, NAX012, NAX014, and NAX018, and we tested their effects on two human colon carcinoma cell lines, that is, HCT116 and SW613-B3, which are characterized by wt and mutated p53, respectively. We observed that cell proliferation is more affected by cell treatment with the derivatives than with the lead compound; moreover, the derivatives proved to induce cell cycle arrest and cell death through apoptosis, thus suggesting that they could be promising anticancer drugs. Finally, we detected typical signs of autophagy in cells treated with berberine derivatives.

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Section: Resultsmentioning

confidence: 99%

Multiple Effects of Berberine Derivatives on Colon Cancer Cells

Ortiz

Tillhon

Parks

et al. 2014

BioMed Research International

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“…The antioxidant capacity of berberine has demonstrated both direct (Jang et al, 2009;Bashir and Gilani, 2011) and indirect activities (Hwang et al, 2002;Tan et al, 2007). Recently, berberine has been structurally modified to yield new derivatives which are able to improve their biological functions: antibacterial (Zuo et al, 2012;Zhang et al, 2013), antifungal (Liu et al, 2014), antiprotozoal (Bahar et al, 2011), and anticancer activities (Zhang et al, 2012;Lo et al, 2013).…”

Section: Antioxidant Effect Of Berberine and Its Phenolic Derivativesmentioning

confidence: 99%

Antioxidant Effect of Berberine and its Phenolic Derivatives Against Human Fibrosarcoma Cells

Pongkittiphan¹,

Chavasiri²,

Supabphol³

2015

Asian Pacific Journal of Cancer Prevention

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“…The isoquinoline alkaloids constitute a novel class of potential therapeutics owing to their wide range of pharmacological activities. As berberine is an important alkaloid of this group with potential anticancer activity, many studies on its derivatives are currently in progress in several laboratories to enhance its efficacy (Basu et al ., ; Liu et al ., ; Endoh et al ., ; Lo et al ., ; Marverti et al ., ; Pierpaoli et al ., ; Zhang et al ., ; Bhowmik et al ., ; Ortiz et al ., ). Various 9 and 13‐substituted berberine derivatives have been shown to induce G‐quadruplex formation and inhibit telomerase activity (Franceschin et al ., ; Gornall et al ., ; Ma et al ., ; Gornall et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Recognition of human telomeric G‐quadruplex DNA by berberine analogs: effect of substitution at the 9 and 13 positions of the isoquinoline moiety

Bhowmik

Fiorillo²,

Lombardi³

et al. 2015

J of Molecular Recognition

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G-quadruplex forming sequences are widely distributed in human genome and serve as novel targets for regulating gene expression and chromosomal maintenance. They offer unique targets for anticancer drug development. Here, the interaction of berberine (BC) and two of its analogs bearing substitution at 9 and 13-position with human telomeric G-quadruplex DNA sequence has been investigated by biophysical techniques. Both the analogs exhibited several-fold higher binding affinity than berberine. The Scatchard binding isotherms revealed non-cooperative binding. 9-ω-amino hexyl ether analog (BC1) showed highest affinity (1.8 × 10(6) M(-1)) while the affinity of the 13-phenylpropyl analog (BC2) was 1.09 × 10(6) M(-1). Comparative fluorescence quenching and polarization anisotropy of the emission spectra gave evidence for a stronger stacking interaction of the analogs compared to berberine. The thiazole orange displacement assay has clearly established that the analogs were more effective in displacing the end stacked dye in comparison to berberine. However, the binding of the analogs did not induce any major structural perturbation in the G-quadruplex structure, but led to higher thermal stability. Energetics of the binding indicated that the association of the analogs was exothermic and predominantly entropy driven phenomenon. Increasing the temperature resulted in weaker binding; the enthalpic contribution increased and the entropic contribution decreased. A small negative heat capacity change with significant enthalpy-entropy compensation established the involvement of multiple weak noncovalent interactions in the binding process. The 9-ω-amino hexyl ether analog stabilized the G-quadruplex structure better than the 13-phenyl alkyl analog.

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Synthesis and anticancer activity of a novel series of 9-O-substituted berberine derivatives: A lipophilic substitute role

Cited by 59 publications

References 24 publications

Multiple Effects of Berberine Derivatives on Colon Cancer Cells

Multiple Effects of Berberine Derivatives on Colon Cancer Cells

Antioxidant Effect of Berberine and its Phenolic Derivatives Against Human Fibrosarcoma Cells

Recognition of human telomeric G‐quadruplex DNA by berberine analogs: effect of substitution at the 9 and 13 positions of the isoquinoline moiety

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