Synthesis and Cancer Chemopreventive Activity of Zapotin, a Natural Product from <i>Casimiroa </i><i>edulis</i>

Maiti, Arup; Cuendet, Muriel; Kondratyuk, Tamara P.; Croy, Vicki L.; Pezzuto, John M.; Cushman, Mary

doi:10.1021/jm060915+

Cited by 29 publications

(22 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IC 50 values were generated from the results of five serial dilutions of tested derivatives in duplicate. Standard inhibitors of ODC activity include apigenin, IC 50 = 6.0 μM, menadione, IC 50 = 8.3 μM, and deguelin, IC 50 = 0.1 μM [85]. …”

Section: Methodsmentioning

confidence: 99%

Resveratrol derivatives as promising chemopreventive agents with improved potency and selectivity

Kondratyuk

Park

Marler

et al. 2011

Molecular Nutrition Food Res

Self Cite

View full text Add to dashboard Cite

Despite scores of investigations, the actual impact of resveratrol (3,5,4′-trihydroxy-trans-stilbene) on human health, as a dietary component or supplement, remains moot. This is due to many factors, such as relatively low potency, pleiotropic mechanisms, and rapid metabolism. Nonetheless, as a promiscuous molecule that interacts with numerous targets, resveratrol can be viewed as a scaffold for designing structural relatives potentially capable of mediating more intense responses with greater mechanistic stringency. We currently report the synthesis and biological evaluation of 92 stilbene analogs. The compounds were tested with in vitro assays for activation of quinone reductase 1, inhibition of QR2, nitric oxide production, aromatase, NFκB, TPA-induced ornithine decarboxylase, or cyclooxygenase-1 and -2, quenching of 2,2-diphenyl-1-picrylhydrazyl free radical, interaction with estrogen receptors, and as antiproliferative agents. Several compounds were found to mediate responses with much greater potency than resveratrol; some mediated pleiotropic responses, as is the case with the parent molecule, but others were highly specific or totally inactive. When administered to rats, higher serum concentrations and greater stability was demonstrated with prototype lead molecules. Due to structural simplicity, facile syntheses are available for large-scale production. These data support the promise of more advanced development of novel resveratrol derivatives as drug entities.

show abstract

Section: Methodsmentioning

confidence: 99%

Resveratrol derivatives as promising chemopreventive agents with improved potency and selectivity

Kondratyuk

Park

Marler

et al. 2011

Molecular Nutrition Food Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…(4) (C)), contained in the edible fruit Casimiroa edulis, was found to induce apoptosis in cultured human promyelocytic leukemia cells (HL-60 cells) [95]. In addition, this compound was verified to inhibit the enzyme ornithine decarboxylase, essential for the synthesis of biogenic polyamines (putrescine, spermidine and spermine) and therefore for cell growth and differentiation, in human bladder carcinoma cells.…”

Section: Chromones As Bioactive Agentsmentioning

confidence: 99%

Bioactive Chromone Derivatives – Structural Diversity

Machado¹,

Marques

2010

CBC

View full text Add to dashboard Cite

Chromones (1-benzopyran-4-ones) and chromone derivatives are naturally occurring compounds ubiquitously found in the plant kingdom, and therefore present in representative amounts in a normal human diet. These phytochemicals possess a wide spectrum of biological activities -such as anti-inflammatory, antifungal, antimicrobial, antiviral, antitumour and anticancer -mainly due to their well-recognised antioxidant properties, which stem from their ability to neutralise active forms of oxygen and to cut off free radical processes.Since oxidative stress is known to be the basis for numerous severe pathologies, from cardiovascular and neurodegenerative disorders to cancer, the development of effective antioxidant agents from natural origin (namely dietary constituents) has been the object of vigorous research in the last decade, in view of establishing novel chemopreventive strategies against such diseases which are nowadays the main cause of death worldwide. In fact, the chromone moiety is an important element of pharmacophores of many biologically active molecules displaying diverse medicinal applications.These potential health benefits arising from the antioxidant activity of chromone derivatives are ruled by strict structureactivity/structure-property relationships, which, apart from determining their biological action, modulate their systemic distribution and bioavailability in sites of oxidation within the cell.The present work aims at reviewing the main reported studies on the cytoprotective and anticancer activities of chromone derivatives, with particular emphasis on the effect of their structural features and conformational behaviour on activity, which is the basis of a tailored design of novel chromone-based antioxidants for chemopreventive and chemotherapeutic use.

show abstract

“…Chromone-type compounds are well-known for their variety of biological properties, that include antitumor [4][5][6][7][8][9][10][11][12][13][14][15], hepatoprotective [16], antioxidant [17][18][19][20][21], anti-inflammatory [22][23][24][25], cardioprotective [26], antimicrobial [27,28] and antiviral activities [29,30]. The vast range of biological effects associated with these structural skeletons has led to substantial research devoted to the isolation from natural resources, synthesis and transformation of chromone derivatives and also to biological evaluation with emphasis on their potential medicinal applications.…”

Section: Introductionmentioning

confidence: 99%