John M. Pezzuto's research while affiliated with Western New England University and other places

Publications (548)

Article
The benefits of fruit and vegetable dietary consumption are largely defined in epidemiological terms. Relatively little is known about the discrete effects on metabolic pathways elicited by individual dietary fruits and vegetables. To address this, grape powder was added to both a standard and a high-fat Western pattern diet given to 10-week-old fe...
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A key objective of this study was to explore the potential of dietary grape consumption to modulate adverse effects caused by a high-fat (western-pattern) diet. Female C57BL/6J mice were purchased at six-weeks-of-age and placed on a standard (semi-synthetic) diet (STD). At 11 weeks-of-age, the mice were continued on the STD or placed on the STD sup...
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(1) Background: Adverse effects of a chronic high-fat diet (HFD) on murine behavior, cognition, and memory are well established. Polyphenols such as resveratrol, anthocyanins, and flavonoids, that are known for antioxidative and anti-inflammatory properties, are present in grapes. The objective of this work was to determine if the dietary intake of...
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Context Carcinogenesis causes much human misery. It is a process involving multistage alterations. Medicinal plants are candidates for beneficial anticancer agents. Objectives Investigation of anticancer proficiencies of the plant Dicliptera roxburghiana. Material and methods Crude extract and derived fractions were inspected for their inhibitory...
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Main conclusion Metabolites in Rafflesia -infected and non-infected Tetrastigma were compared which may have applications in Rafflesia propagation. Benzylisoquinoline alkaloids, here reported for the first time in Vitaceae, were abundant in non-infected shoots and may be a form of defense. In Rafflesia -infected shoots, oxylipins, which mediate imm...
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The unending morbidity and mortality that results from cancer, as well as adverse reactions due to chemotherapy and the enormous economic burden of treatment and hospitalization, advocates for the necessity of chemopreventive measures. Cancer chemoprevention refers to the use of agents capable of reversing, reducing, or slowing down the pathology o...
Article
Datura innoxia Mill., Solanaceae, an underexplored ethnomedicinal plant, has been empirically evaluated in the current study for the isolation of bioactive agents. A crude extract of D. innoxia leaves was subjected to normal-phase medium pressure and vacuum liquid chromatography which led to the purification of a withanolide, isowithametelin. The c...
Chapter
Throughout this book the power of combination chemoprevention is highlighted. Even individual agents that function by virtue of pleiotropic mechanisms of action portray a combination effect. In this final chapter, we offer a brief perspective on the concept of combining numerous (e.g., 10–25) dietary agents for the creation of a cocktail capable of...
Book
This book discusses the efficacy of various naturally occurring chemopreventive agents in preventing or delaying cancer. It focuses on the holistic chemopreventive concept, demonstrating the relevant response is the combined effect of a series of compounds that alone have been shown to have some effect in different experimental models. Written by...
Article
Solvent fractions from leaf and bark extracts of Vaccinium leschenaultii were screened for their antioxidant, cell viability, and nitric oxide (NO) inhibitory potential. Antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), total antioxidant activity (TAC) and Oxygen Radical Antioxidant Capacity (ORAC) assays. Sulforhodami...
Article
In this article we have comprehensively reported the synthesis, complete chemical characterization (FTIR, multinuclear NMR, single crystal XRD, CHNS, AAS) and biological applications of seventeen ferrocene incorporated selenoureas. Biological applications include comparative DNA binding studies (with, cyclic voltammetry), antioxidant activities (DP...
Article
In previous studies, withanolides isolated from Physalis peruviana were found to exhibit anti-inflammatory potential by suppressing nitrite production induced by lipopolysaccharide (LPS) treatment. Currently, we selected two of the most potent compounds, 4β-hydroxywithanolide E (1) and physalactone (2), to examine the underlying mechanism of action...
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Resveratrol was first isolated in 1939 by Takaoka from Veratrum grandiflorum O. Loes. Following this discovery, sporadic descriptive reports appeared in the literature. However, spurred by our seminal paper published nearly 60 years later, resveratrol became a household word and the subject of extensive investigation. Now, in addition to appearing...
Article
Background/aim: There is an unmet clinical need to develop new anticancer and chemopreventive agents. The aim of the present study was to identify β-carboline derivatives with cancer chemopreventive and therapeutic potential. Materials and methods: Forty-eight tetrahydro-β-carboline derivatives were synthesized and evaluated for their anticancer...
Article
Toranja ‘Burarama’, Citrus maxima (Burm.) Merr. (Citrus grandis), is a new citrus discovered in the State of Espírito Santo, Brazil. As several varieties of citrus are known to possess antioxidant and cancer chemopreventive properties, the aim of the study was to evaluate in vitro if this Toranja possess these properties. The antioxidant activity,...
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LC-UV/MS-based metabolomic analysis of the Hawaiian endophytic fungus Paraphaeosphaeria neglecta FT462 led to the identification of four unique mercaptolactated γ-pyranol–γ-lactams, paraphaeosphaerides E–H (1–4) together with one γ-lactone (5) and the methyl ester of compound 2 (11). The structures of the new compounds (1–5 and 11) were elucidated...
Article
In our ongoing effort of discovering anticancer and chemopreventive agents, a series of 2-arylindole derivatives were synthesized and evaluated toward aromatase and quinone reductase 1 (QR1). Biological evaluation revealed that several compounds (e.g., 2d, IC50 = 1.61 μM; 21, IC50 = 3.05 μM; and 27, IC50 = 3.34 μM) showed aromatase inhibitory activ...
Article
Two new compounds heliotropiumides A (1) and B (2), phenolamides each with an uncommon carbamoyl putrescine moiety, were isolated from the seeds of a naturalized Hawaiian higher plant, Heliotropium foertherianum Diane & Hilger in the borage family, which is widely used for the treatment of ciguatera fish poisoning. The structures of compounds 1 and...
Article
The Daniel K. Inouye College of Pharmacy, during a historic event in Spring 2016, graduated the first two students in the Pacific region to earn a PhD in pharmaceutical sciences at the University of Hawai'i at Hilo. The college offers PhD programs in these five disciplines: Cancer Biology, Medicinal Chemistry, Pharmaceutics, Pharmacognosy, and Phar...
Article
Bioassay-guided fractionation of the dichloromethane extract from the apical bud of Gardenia sootepenesis Hutch. (Rubiaceae) led to the isolation of four new cycloartane triterpenes, sootepins F-I (1-4), along with four known derivatives (5-8). The structures of the new compounds were determined by 1D and 2D NMR experiments and by comparison of the...
Article
Multiple myeloma (MM) continues to claim the lives of a majority of patients. MM cancer stem cells (CSCs) have been demonstrated to sustain tumor growth. Due to their ability to self-renew and to express detoxifying enzymes and efflux transporters, MM-CSCs are rendered highly resistant to conventional therapies. Therefore, managing MM-CSCs characte...
Article
Mol. Nutr. Food Res. 2016, 60, 1482–1500. DOI: 10.1002/mnfr.201500977 It is shown that 4β‐hydroxywithanolide E (4HWE) isolated from Physalis peruviana arrests the growth of HT‐29 colon cancer cells in the G0/G1 phase of the cell cycle at low concentrations (0.5 and 1 μM) and induces apoptosis at higher concentrations (5 and 10 μM). Growth arrest is...
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As with human beings, dogs suffer from the consequences of cancer. We investigated the potential of a formulation comprised of resveratrol, ellagic acid, genistein, curcumin and quercetin to modulate biomarkers indicative of disease prevention. Dog biscuits were evaluated for palatability and ability to deliver the chemopreventive agents. The exten...
Article
A new fatty acid ester disaccharide, 2-O-(β-d-glucopyranosyl)-1-O-(2E,4Z,7Z)-deca-2,4,7-trienoyl-β-d-glucopyranose (1), a new ascorbic acid derivative, 2-caffeoyl-3-ketohexulofuranosonic acid γ-lactone (2), and a new iridoid glycoside, 10-dimethoxyfermiloside (3), were isolated along with 13 known compounds (4-16) from fermented noni fruit juice (M...
Article
Context: Endophytic fungi, being a prolific source of bioactive secondary metabolites, are of great interest for natural product discovery. Objective: Isolation and partial characterization of endophytic fungi inhabiting the leaves and woody parts of Taxus fuana Nan Li & R.R. Mill. (Taxaceae) and evaluation of biological activity. Materials and met...
Article
Three new withanolides, physaperuvin G (1), physaperuvins I–J (2–3), along with seven known derivatives (4–10), were isolated from the aerial parts of Physalis peruviana. The structures of 1–3 were determined by NMR, X-ray diffraction, and mass spectrometry. Compounds 1–10 were evaluated in lipopolysaccharide (LPS)-activated murine macrophage RAW 2...
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Litsea verticillata Hance (Lauraceae), a Chinese medicine used to treat swelling caused by injury or by snake bites, was the first plant identified by our National Institutes of Health (NIH)-funded International Cooperative Biodiversity Group (ICBG) project to exhibit anti-HIV activities. From this plant, we discovered a class of 8 novel litseane c...
Article
Scope: Physalis peruviana (Solanaceae) is used for culinary and medicinal purposes. We currently report withanolides, isolated from P. peruviana, inhibit the growth of colon cancer monolayer and spheroid cultures. A detailed mechanistic evaluation was performed with 4β-hydroxywithanolide E (4HWE). Methods and results: Treatment of HT-29 cells wi...
Article
Two new heteroleptic palladium(II) complexes have been synthesized by reacting equimolar quantities of palladium(II) chloride, sodium 4-(2-methoxyphenyl)piperazine-1-carbodithioate and diphenyl-p-tolylphosphine (1) or tri-p-tolylphosphine (2). Complexes 1 and 2 have been characterized using elemental analysis, Fourier transform infrared spectroscop...
Book
This book offers a thorough review of the scientific research that links the consumption of grapes to better health. The book starts with a basic review of grape biology, including the key families of phytochemicals found in grapes, and where they are found. An overview of the rationale for and subsequent creation of a standardized grape powder for...
Article
Traditional medicinal plants are often used for both the prevention and the treatment of local diseases. Taking into consideration the medicinal importance of Hedera nepalensis within local Pakistani traditions, the present study was undertaken to analyze the in vitro cancer chemopreventive and cytotoxic properties of the plant. The in vitro cancer...
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Throughout history, natural products have played a dominant role in the treatment of human ailments. For example, the legendary discovery of penicillin transformed global existence. Presently, natural products comprise a large portion of current-day pharmaceutical agents, most notably in the area of cancer therapy. Examples include taxol, vinblasti...
Article
Chemical investigation of an endophytic fungus Chaetomium globosum isolated from leaves of Wikstroemia uva-ursi led to the isolation of two new azaphilones, chaetoviridins J and K (1 and 3), along with five known derivatives (2 and 4-7). The structures of azaphilones were determined by NMR, X-ray diffraction, Mosher's method, and CD analysis. The i...
Article
(E)-4-(3,5-Dimethoxystyryl)phenyl acetate (Cmpd1) is a resveratrol analog that preferentially inhibits glioma, breast and pancreatic cancer cell growth, with IC50 values of 6-19 μM. Notably, the human U251MG glioblastoma tumor line is most sensitive, with an IC50 of 6.7 μM, compared to normal fibroblasts, with IC50 >20 μM. Immunoblotting analysis s...
Article
Aberrantly active nuclear factor-κB (NF-κB) and signal transducer and activator of transcription (STAT3) protein are critical factors that regulate tumor processes. Convincing evidence shows the association between NF-κB and STAT3 plays integrated role in promoting cancer development. Consequently, inhibitors of NF-κB and STAT3 isolated from natura...
Article
For a compound to be a best chemopreventive agent it should be a descent DNA binder and at the same time should be active against any of the three stages of carcinogenesis i.e. cancer initiation, cancer propagation and tumor growth. Most of the problems associated with chemotherapy can be overcome if the chemopreventive agent is active against all...
Article
In partnership with the Hawai'i Journal of Medicine & Public Health, the Daniel K. Inouye College of Pharmacy (DKICP) is pleased to provide Scripts on a regular basis. In the inaugural "Script," a brief history of the profession in Hawai'i was presented up to the founding of the DKICP, Hawai'i's only academic pharmacy program. In this second part o...
Article
In addition to thousands of research papers related to resveratrol (RSV), approximated 300 review articles have been published. Earlier research tended to focus on pharmacological activities of RSV related to cardiovascular systems, inflammation, and carcinogenesis/cancer development. More recently, the horizon has been broadened by exploring the p...
Article
The Daniel K. Inouye College of Pharmacy is the newest professional school to be established in the State of Hawai'i. The College is based at the University of Hawai'i at Hilo, but faculty and students are located and practice on every major island. The mission of the College is to serve the entire Pacific Region. Having reached a respectable level...
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Hedychium coronarium J. Koenig, Zingiberaceae, is a medicinal plant popularly used to treat inflammatory conditions in different countries. Three labdane diterpenes [isocoronarin D (1), methoxycoronarin D (2), ethoxycoronarin D (3)] and benzoyl eugenol (4) were isolated from rhizomes and their chemopreventive potential was evaluated using in vitro...
Article
New compounds 18-nor-3,17-dihydroxyspongia-3,13(16),14-trien-2-one (1), 18-nor-3,5,17-trihydroxyspongia-3,13(16),14-trien-2-one (2), and spongiapyridine (3) and the known compound 17-hydroxy-4-epi-spongialactone A (4) were isolated from an Indonesian sponge of the genus Spongia. The structures of 1-3 were deduced by analyses of physical and spectro...
Article
Two new and five known withanolides (jaborosalactones 2, 3, 4, 5, and 24) were isolated from the leaves of Jaborosa runcinata Lam. We also obtained some derivatives from jaborosalactone 5, which resulted to be the major isolated metabolite. The natural compounds as well as derivatives were evaluated for their antiproliferative activity and the indu...
Article
Four new undecose nucleosides (herbicidin congeners), three known herbicidins, and 9-(β-d-arabinofuranosyl)hypoxanthine (Ara-H) were isolated from the organic extract of a fermentation culture of Streptomyces sp. L-9-10 using proton NMR-guided fractionation. Their structures were elucidated on the basis of comprehensive 1D and 2D NMR and mass spect...
Article
A new lignan, vitexkarinol (1), as well as a known lignan, neopaulownin (2), a known chalcone, 3-(4-hydroxyphenyl)-1-(2,4,6-trimethoxyphenyl)-2-propen-1-one (3), two known dehydroflavones, tsugafolin (4) and alpinetin (5), two known dipeptides, aurantiamide and aurantiamide acetate, a known sesquiterpene, vemopolyanthofuran, and five known caroteno...
Article
In previous studies, (R)-2-isobutyl 3-methyl 3,4-dihydro-1H-pyrido[3,4-b]indole-2,3(9H)-dicarboxylate (1), a callophycin A derivative, was found to strongly inhibit nitrite production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, while (R)- or (S)-callophycin A showed only weak inhibition. We currently report additional studies to define...
Article
Introduction: There is currently a wealth of information on the effects of resveratrol and its derivatives in therapeutic, cosmetic and nutraceutical patent applications. Structure-activity studies of the resveratrol scaffold provide a foundation for the development of new analogs with potent activity or other beneficial properties. Ongoing resear...
Article
Vermelhotin exhibited potential anti-inflammatory activity through inhibition of nitric oxide production (IC50 = 5.35 +/- 0.59 mu M) in LPS-stimulated RAW 264.7 macrophage cells. Vermelhotin suppressed expression of inducible nitric oxide synthase (iNOS) at mRNA and protein levels, in a dose-dependent manner. Mechanistic studies revealed that verme...
Article
The synthesis of new imidazo[2,1-b]thiazoles bearing phenolic groups is reported. These compounds and some previously described analogs were evaluated as antioxidant agents with three chemical model systems, and cancer chemopreventive potential was examined by inhibition of NO production, TNF-α activated NFκB activity, and aromatase activity, as we...
Article
Although resveratrol can modulate multiple stages of carcinogenesis, by most common standards it is not a good drug candidate. Resveratrol lacks potency, high efficacy, and target specificity; it is rapidly metabolized and serum concentrations are low. Using resveratrol as a scaffold, we produced over 100 derivatives, some of which have target spec...
Article
A library of 2-phenylindole derivatives is synthesized by one-pot palladium-catalyzed Sonogashira-type alkynylation reactions and base-assisted cycloaddition reactions.
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Agents capable of inducing phase II enzymes such as quinone reductase 1 (QR1) are known to have the potential of mediating cancer chemopreventive activity. As part of a program to discover novel phase II enzyme-inducing molecules, we identified a marine-derived actinomycete strain (CNJ-878) that exhibited activity with cultured Hepa 1c1c7 cells. Ba...
Article
Nuclear receptors, such as the retinoid X receptor (RXR), are proteins that regulate a myriad of cellular processes. Molecules that function as RXR agonists are of special interest for the prevention and control of carcinogenesis. The majority of these ligands possess an acidic moiety that is believed to be key for RXR activation. This communicatio...
Article
Significance: Oxidative stress resulting from excessive reactive oxygen/nitrogen/electrophilic species (ROS/RNS/RES) can lead to diseases such as cancer. The health benefits of dietary fruits and vegetables with antioxidant potential have received a great deal of attention. On the other hand, marine botanicals have been less well characterized and...
Article
Bioassay-directed isolation and purification of the crude extract of Withania coagulans, using two assays for cancer chemopreventive mechanisms, led to the isolation of three new steroidal lactones, withacoagulin G (1), withacoagulin H (2), and withacoagulin I (3), along with six known derivatives (4-9). The structures and absolute stereochemistry...
Article
Context: Natural products are a very productive source of leads for the development of medicines. Six Pakistani plants were chosen for study based on ethnobotanical data. Objective: Exploration of important medicinal plants of Pakistan for cancer treatment. Materials and methods: The crude extracts of the six plants and their fractions were te...
Article
Development of small molecule drug-like inhibitors blocking both nitric oxide synthase and NFκB could offer a synergistic therapeutic approach in the prevention and treatment of inflammation and cancer. During the course of evaluating the biological potential of a commercial compound library, 2-phenylindole () displayed inhibitory activity against...
Article
Lead on! In the course of screening flavonoid and resveratrol libraries, abyssinone II, a naturally occurring prenylated flavonoid, was found to exhibit relatively good antitubercular and antibacterial activity. Preliminary mechanistic studies revealed that abyssinone II hyperpolarizes the bacterial membrane potential and inhibits the biosynthesis...
Article
Syrbactins belong to a recently emergent class of bacterial natural product inhibitors that irreversibly inhibit the proteasome of eukaryotes by a novel mechanism. The total syntheses of the syrbactin molecules syringolin A, syringolin B, and glidobactin A have been achieved, which allowed the preparation of syrbactin-inspired derivatives, such as...
Article
Bioassay-guided fractionation of the hexane extract from the flowers of Vernonia cinerea (Asteraceae) led to the isolation of a new sesquiterpene lactone, 8α-hydroxyhirsutinolide (2), and a new naturally occurring derivative, 8α-hydroxyl-1-O-methylhirsutinolide (3), along with seven known compounds (1 and 4-9). The structures of the new compounds w...
Article
Several lactone- and lactam-based neoflavonoids and tetrahydroquinolones were synthesized and evaluated for cancer chemopreventive studies using cell and molecular target-based in vitro bioassays, namely NFκB, aromatase, and quinone reductase 1. These analogs blocked TNF-α-induced NFκB activation in a dose-dependent manner with IC(50) values in the...
Article
Activation of the retinoid X receptor (RXR), which is involved in cell proliferation, differentiation, and apoptosis, is a strategy for cancer chemotherapy and chemoprevention, and 3-amino-6-(3'-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6-36) (3) is among the few RXR ligands known. The presently reported studies of 3 include its b...
Article
Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Previously, we reported interesting pharmacological responses mediated with indenoisoquinolines, including cytotoxic effects mediated by the topoisomerase I inhibitor 6-(3-aminopropyl)-9-methoxy-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione (AM9-79). We currently d...
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The measurement of nitric oxide in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells is used as a model for evaluating the anti-inflammatory or chemopreventive potential of substances. Thienodolin, isolated from a Streptomyces sp. derived from Chilean marine sediment, inhibited nitric oxide production in LPS-stimulated RAW 264.7 cells (IC50 = 17....