Phloroglucinol compounds of natural origin: Synthetic aspects

Singh, Inder Pal; Sidana, Jasmeen; Bharate, Sandip B.; Foley, William J.

doi:10.1039/b914364p

Cited by 195 publications

(112 citation statements)

References 115 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…Phloroacetophenone analogues which are intermediates of the flavonoid biosynthetic pathway 1) have shown in vitro cytotoxicity against several cancer cell lines. 2) In fact, flavonoid polyphenols from dietary plants are known to exert a variety of effects.…”

mentioning

confidence: 99%

Geranyl Derivative of Phloroacetophenone Induces Cancer Cell-Specific Apoptosis through Bax-Mediated Mitochondrial Pathway in MCF-7 Human Breast Cancer Cells

Cho

Park

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Plant-derived polyhenols inhibit cancer cell proliferation and induce apoptosis. Recently, prenylflavonoids and alkyl-phloroacetophenones have been reported for their in vitro antitumor activity. In the present study, we examined the cytotoxic activity of prenyl (3-PAP) and geranyl (3-GAP) derivatives of phloroacetophenone, and xanthohumol (XN), a prenyl-chalcone, in human breast cancer (MCF-7) and human sarcoma (HT1080) cell lines in vitro. 3-GAP showed the strongest cytotoxicity in these cell lines with IC 50 values of less than 10 µM. In addition, we report that 3-GAP is a more potent anti-cancer agent for breast cancer than XN which is a well-known anticancer flavonoid. Moreover, 3-GAP did not induce cytotoxicity in the normal cell line, TCMK-1, whereas 3-PAP and XN significantly reduced TCMK-1 cell viability. In 3-GAP-treated MCF-7 cells, nuclear accumulation and transcriptional activity of p53 were increased. In addition, proapoptotic Bax but not B-cell lymphoma 2 (Bcl-2) expression was increased by 3-GAP. In accordance with the Bax increase, 3-GAP induced mitochondrial cytochrome c release and activated caspase-9, an initiator of the caspase cascade. In the MCF-7 cell line which does not express caspase-3, activation of caspase-7, a member of the caspase-3 subfamily, was increased by 3-GAP. The present results indicate that synthetic 3-GAP is a safe and effective anti-cancer agent, and the Bax-mediated mitochondrial pathway is the main apoptosis signaling pathway of 3-GAP in MCF-7 cells.

show abstract

mentioning

confidence: 99%

Geranyl Derivative of Phloroacetophenone Induces Cancer Cell-Specific Apoptosis through Bax-Mediated Mitochondrial Pathway in MCF-7 Human Breast Cancer Cells

Cho

Park

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…In view of the rich repertoire of cyclization strategies documented in the synthetic studies towards PPAPs [2] and the synthetic versatility of alkynyl ketone 27, as a proof-ofprincipal study we were first attracted to the efficiency of the intramolecular aldol reaction that had been demonstrated previously (Scheme 4). [5] In this context, partial reduction of the terminal alkyne to the corresponding alkene was found to be capricious under a variety of conditions.…”

Section: Resultsmentioning

confidence: 99%

“…Among them, (+)-hyperforin (1), nemorosone (2), and garsubellin A (3) instigated significant interest from the synthetic community mainly because of their challenging molecular architecture in conjunction with their promising antidepressant, antimalarial, antibacterial, antioxidant, and antineurodegenerative activities (Figure 1). …”

Section: Introductionmentioning

confidence: 99%

“…[1] Significant progress have been made in the last decade towards the synthesis of a diverse array of PPAP congeners; [2] however, asymmetric entry to the densely functionalized bicyclo[3.3.1]nonane-2,4,9-trione or bicyclo[3.2.1]octane-2,4,8-trione core of the PPAPs remains a formidable synthetic challenge. Evidently, only four asymmetric total syntheses of (+)-and (-)-clusianone, [3] (+)-hyperibone K, [4] and enthyperforin [5] have been accomplished, together with sporadic reports on asymmetric model studies.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Chiral‐Pool‐Based Approach to the Core Structure of (+)‐Hyperforin

Richard

Chen

2011

Eur J Org Chem

View full text Add to dashboard Cite

show abstract

“…To our knowledge, we demonstrate for the first time that Fragaria spp. plants are able to synthesize and accumulate APGs, compounds with exciting pharmacological properties (Singh et al, 2010), due to the catalytic properties of bifunctional chalcone synthase/valerophenone synthase enzymes. APGs might be important physiologically active metabolites in Fragaria spp.…”

Section: Resultsmentioning

confidence: 99%

Acylphloroglucinol biosynthesis in strawberry fruit

et al. 2015

View full text Add to dashboard Cite

ORCID IDs: 0000-0001-6609-7034 (J.S.); 0000-0002-9753-3967 (W.S.).Phenolics have health-promoting properties and are a major group of metabolites in fruit crops. Through reverse genetic analysis of the functions of four ripening-related genes in the octoploid strawberry (Fragaria 3 ananassa), we discovered four acylphloroglucinol (APG)-glucosides as native Fragaria spp. fruit metabolites whose levels were differently regulated in the transgenic fruits. The biosynthesis of the APG aglycones was investigated by examination of the enzymatic properties of three recombinant Fragaria vesca chalcone synthase (FvCHS) proteins. CHS is involved in anthocyanin biosynthesis during ripening. The F. vesca enzymes readily catalyzed the condensation of two intermediates in branched-chain amino acid metabolism, isovaleryl-Coenzyme A (CoA) and isobutyryl-CoA, with three molecules of malonyl-CoA to form phlorisovalerophenone and phlorisobutyrophenone, respectively, and formed naringenin chalcone when 4-coumaroyl-CoA was used as starter molecule. Isovaleryl-CoA was the preferred starter substrate of FvCHS2-1. Suppression of CHS activity in both transient and stable CHSsilenced fruit resulted in a substantial decrease of APG glucosides and anthocyanins and enhanced levels of volatiles derived from branched-chain amino acids. The proposed APG pathway was confirmed by feeding isotopically labeled amino acids. Thus, Fragaria spp. plants have the capacity to synthesize pharmaceutically important APGs using dual functional CHS/ (phloriso)valerophenone synthases that are expressed during fruit ripening. Duplication and adaptive evolution of CHS is the most probable scenario and might be generally applicable to other plants. The results highlight that important promiscuous gene function may be missed when annotation relies solely on in silico analysis.

show abstract

Phloroglucinol compounds of natural origin: Synthetic aspects

Abstract: This review covers the synthetic aspects of various naturally occurring phloroglucinols, describing syntheses of 42 compounds and citing 137 references.

Cited by 195 publications

References 115 publications

Geranyl Derivative of Phloroacetophenone Induces Cancer Cell-Specific Apoptosis through Bax-Mediated Mitochondrial Pathway in MCF-7 Human Breast Cancer Cells

Geranyl Derivative of Phloroacetophenone Induces Cancer Cell-Specific Apoptosis through Bax-Mediated Mitochondrial Pathway in MCF-7 Human Breast Cancer Cells

A Chiral‐Pool‐Based Approach to the Core Structure of (+)‐Hyperforin

Acylphloroglucinol biosynthesis in strawberry fruit

Contact Info

Product

Resources

About