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(12) United States Patent (10) Patent No.: US 9.421,180 B2 Zielinski Et Al
USOO9421 180B2 (12) United States Patent (10) Patent No.: US 9.421,180 B2 Zielinski et al. (45) Date of Patent: Aug. 23, 2016 (54) ANTIOXIDANT COMPOSITIONS FOR 6,203,817 B1 3/2001 Cormier et al. .............. 424/464 TREATMENT OF INFLAMMATION OR 6,323,232 B1 1 1/2001 Keet al. ............ ... 514,408 6,521,668 B2 2/2003 Anderson et al. ..... 514f679 OXIDATIVE DAMAGE 6,572,882 B1 6/2003 Vercauteren et al. ........ 424/451 6,805,873 B2 10/2004 Gaudout et al. ....... ... 424/401 (71) Applicant: Perio Sciences, LLC, Dallas, TX (US) 7,041,322 B2 5/2006 Gaudout et al. .............. 424/765 7,179,841 B2 2/2007 Zielinski et al. .. ... 514,474 (72) Inventors: Jan Zielinski, Vista, CA (US); Thomas 2003/0069302 A1 4/2003 Zielinski ........ ... 514,452 Russell Moon, Dallas, TX (US); 2004/0037860 A1 2/2004 Maillon ...... ... 424/401 Edward P. Allen, Dallas, TX (US) 2004/0091589 A1 5, 2004 Roy et al. ... 426,265 s s 2004/0224004 A1 1 1/2004 Zielinski ..... ... 424/442 2005/0032882 A1 2/2005 Chen ............................. 514,456 (73) Assignee: Perio Sciences, LLC, Dallas, TX (US) 2005, 0137205 A1 6, 2005 Van Breen ..... 514,252.12 2005. O154054 A1 7/2005 Zielinski et al. ............. 514,474 (*) Notice: Subject to any disclaimer, the term of this 2005/0271692 Al 12/2005 Gervasio-Nugent patent is extended or adjusted under 35 et al. ............................. 424/401 2006/0173065 A1 8/2006 BeZwada ...................... 514,419 U.S.C. 154(b) by 19 days. 2006/O193790 A1 8/2006 Doyle et al. -
Preclinical Evaluation of Protein Disulfide Isomerase Inhibitors for the Treatment of Glioblastoma by Andrea Shergalis
Preclinical Evaluation of Protein Disulfide Isomerase Inhibitors for the Treatment of Glioblastoma By Andrea Shergalis A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Medicinal Chemistry) in the University of Michigan 2020 Doctoral Committee: Professor Nouri Neamati, Chair Professor George A. Garcia Professor Peter J. H. Scott Professor Shaomeng Wang Andrea G. Shergalis [email protected] ORCID 0000-0002-1155-1583 © Andrea Shergalis 2020 All Rights Reserved ACKNOWLEDGEMENTS So many people have been involved in bringing this project to life and making this dissertation possible. First, I want to thank my advisor, Prof. Nouri Neamati, for his guidance, encouragement, and patience. Prof. Neamati instilled an enthusiasm in me for science and drug discovery, while allowing me the space to independently explore complex biochemical problems, and I am grateful for his kind and patient mentorship. I also thank my committee members, Profs. George Garcia, Peter Scott, and Shaomeng Wang, for their patience, guidance, and support throughout my graduate career. I am thankful to them for taking time to meet with me and have thoughtful conversations about medicinal chemistry and science in general. From the Neamati lab, I would like to thank so many. First and foremost, I have to thank Shuzo Tamara for being an incredible, kind, and patient teacher and mentor. Shuzo is one of the hardest workers I know. In addition to a strong work ethic, he taught me pretty much everything I know and laid the foundation for the article published as Chapter 3 of this dissertation. The work published in this dissertation really began with the initial identification of PDI as a target by Shili Xu, and I am grateful for his advice and guidance (from afar!). -
Natural Chalcones in Chinese Materia Medica: Licorice
Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2020, Article ID 3821248, 14 pages https://doi.org/10.1155/2020/3821248 Review Article Natural Chalcones in Chinese Materia Medica: Licorice Danni Wang ,1 Jing Liang,2 Jing Zhang,1 Yuefei Wang ,1 and Xin Chai 1 1Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China 2School of Foreign Language, Chengdu University of Traditional Chinese Medicine, Sichuan 611137, China Correspondence should be addressed to Xin Chai; [email protected] Received 28 August 2019; Accepted 7 February 2020; Published 15 March 2020 Academic Editor: Veronique Seidel Copyright © 2020 Danni Wang et al. -is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Licorice is an important Chinese materia medica frequently used in clinical practice, which contains more than 20 triterpenoids and 300 flavonoids. Chalcone, one of the major classes of flavonoid, has a variety of biological activities and is widely distributed in nature. To date, about 42 chalcones have been isolated and identified from licorice. -ese chalcones play a pivotal role when licorice exerts its pharmacological effects. According to the research reports, these compounds have a wide range of biological activities, containing anticancer, anti-inflammatory, antimicrobial, antioxidative, antiviral, antidiabetic, antidepressive, hep- atoprotective activities, and so on. -is review aims to summarize structures and biological activities of chalcones from licorice. We hope that this work can provide a theoretical basis for the further studies of chalcones from licorice. -
Biotransformation of Hydroxychalcones As a Method of Obtaining Novel and Unpredictable Products Using Whole Cells of Bacteria
catalysts Article Biotransformation of Hydroxychalcones as a Method of Obtaining Novel and Unpredictable Products Using Whole Cells of Bacteria Joanna Kozłowska 1,* , Bartłomiej Potaniec 1,2 and Mirosław Anioł 1 1 Department of Chemistry, Faculty of Biotechnology and Food Science, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland; [email protected] (B.P.); [email protected] (M.A.) 2 Łukasiewicz Research Network—PORT Polish Center for Technology Development, Stabłowicka 147, 54-066 Wrocław, Poland * Correspondence: [email protected] Received: 27 September 2020; Accepted: 8 October 2020; Published: 12 October 2020 Abstract: The aim of our study was the evaluation of the biotransformation capacity of hydroxychalcones—2-hydroxy-40-methylchalcone (1) and 4-hydroxy-40-methylchalcone (4) using two strains of aerobic bacteria. The microbial reduction of the α,β-unsaturated bond of 2-hydroxy-40- methylchalcone (1) in Gordonia sp. DSM 44456 and Rhodococcus sp. DSM 364 cultures resulted in isolation the 2-hydroxy-40-methyldihydrochalcone (2) as a main product with yields of up to 35%. Additionally, both bacterial strains transformed compound 1 to the second, unexpected product of reduction and simultaneous hydroxylation at C-4 position—2,4-dihydroxy-40-methyldihydrochalcone (3) (isolated yields 12.7–16.4%). During biotransformation of 4-hydroxy-40-methylchalcone (4) we observed the formation of three products: reduction of C=C bond—4-hydroxy-40-methyldihydrochalcone (5), reduction of C=C bond and carbonyl group—3-(4-hydroxyphenyl)-1-(4-methylphenyl)propan-1-ol (6) and also unpredictable 3-(4-hydroxyphenyl)-1,5-di-(4-methylphenyl)pentane-1,5-dione (7). -
Isoliquiritigenin, an Orally Available Natural FLT3 Inhibitor from Licorice, Exhibits Selective Anti–Acute Myeloid Leukemia Efficacy in Vitro and in Vivo
1521-0111/96/5/589–599$35.00 https://doi.org/10.1124/mol.119.116129 MOLECULAR PHARMACOLOGY Mol Pharmacol 96:589–599, November 2019 Copyright ª 2019 by The American Society for Pharmacology and Experimental Therapeutics Isoliquiritigenin, an Orally Available Natural FLT3 Inhibitor from Licorice, Exhibits Selective Anti–Acute Myeloid Leukemia Efficacy In Vitro and In Vivo Zhi-Xing Cao,1 Yi Wen,1 Jun-Lin He, Shen-Zhen Huang, Fei Gao, Chuan-Jie Guo, Qing-Qing Liu, Shu-Wen Zheng, Dao-Yin Gong, Yu-Zhi Li, Ruo-Qi Zhang, Jian-Ping Chen, and Cheng Peng Pharmacy College, Chengdu University of Traditional Chinese Medicine, Ministry of Education Key Laboratory of Standardization Downloaded from of Chinese Herbal Medicine, Key Laboratory of Systematic Research, Development and Utilization of Chinese Medicine Resources in Sichuan Province-Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST, Chengdu, China (Z.-X.C., J.-L.H., C.-J.G., S.-W.Z., D.-Y.G., Y.-Z.L., R.-Q.Z., J.-P.C., C.P.);School of Chinese Medicine, University of Hong Kong, Hong Kong, China (Y.W., F.G., Q.-Q.L., J.-P.C.); College, Shenzhen Institute of Research and Innovation, University of Hong Kong, Shenzhen, China (Y.W., F.G., Q.-Q.L., J.-P.C.); and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China (S.-Z.H.) molpharm.aspetjournals.org Received February 19, 2019; accepted August 20, 2019 ABSTRACT Licorice is a medicinal herb widely used to treat inflammation- AML cells. -
Biosynthesis of Food Constituents: Natural Pigments. Part 2 – a Review
Czech J. Food Sci. Vol. 26, No. 2: 73–98 Biosynthesis of Food Constituents: Natural Pigments. Part 2 – a Review Jan VELÍšEK, Jiří DAVÍDEK and Karel CEJPEK Department of Food Chemistry and Analysis, Faculty of Food and Biochemical Technology, Institute of Chemical Technology in Prague, Prague, Czech Republic Abstract Velíšek J., Davídek J., Cejpek K. (2008): Biosynthesis of food constituents: Natural pigments. Part 2 – a review. Czech J. Food Sci., 26: 73–98. This review article is a part of the survey of the generally accepted biosynthetic pathways that lead to the most impor- tant natural pigments in organisms closely related to foods and feeds. The biosynthetic pathways leading to xanthones, flavonoids, carotenoids, and some minor pigments are described including the enzymes involved and reaction schemes with detailed mechanisms. Keywords: biosynthesis; xanthones; flavonoids; isoflavonoids; neoflavonoids; flavonols; (epi)catechins; flavandiols; leu- coanthocyanidins; flavanones; dihydroflavones; flavanonoles; dihydroflavonols; flavones; flavonols; anthocya- nidins; anthocyanins; chalcones; dihydrochalcones; quinochalcones; aurones; isochromenes; curcuminoids; carotenoids; carotenes; xanthophylls; apocarotenoids; iridoids The biosynthetic pathways leading to the tetrapyr- restricted in occurrence to only a few families of role pigments (hemes and chlorophylls), melanins higher plants and some fungi and lichens. The (eumelanins, pheomelanins, and allomelanins), majority of xanthones has been found in basi- betalains (betacyanins and betaxanthins), and cally four families of higher plants, the Clusiaceae quinones (benzoquinones, naphthoquinones, and (syn. Guttiferae), Gentianaceae, Moraceae, and anthraquinones) were described in the first part of Polygalaceae (Peres et al. 2000). Xanthones can this review (Velíšek & Cejpek 2007b). This part be classified based on their oxygenation, prenyla- deals with the biosynthesis of other prominent tion and glucosylation pattern. -
Pharmacological Effects of Glycyrrhiza Spp. and Its Bioactive Constituents: Update and Review
View metadata, citation and similar papers at core.ac.uk brought to you by CORE PHYTOTHERAPY RESEARCH provided by Qazvin University of Medical Sciences Repository Phytother. Res. 29: 1868–1886 (2015) Published online 13 October 2015 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/ptr.5487 REVIEW Pharmacological Effects of Glycyrrhiza spp. and Its Bioactive Constituents: Update and Review Hossein Hosseinzadeh1 and Marjan Nassiri-Asl2* 1Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran 2Cellular and Molecular Research Center, Department of Pharmacology, School of Medicine, Qazvin University of Medical Sciences, P.O. Box: 341197-5981, Qazvin, Iran The roots and rhizomes of various species of the perennial herb licorice (Glycyrrhiza) are used in traditional medicine for the treatment of several diseases. In experimental and clinical studies, licorice has been shown to have several pharmacological properties including antiinflammatory, antiviral, antimicrobial, antioxidative, antidiabetic, antiasthma, and anticancer activities as well as immunomodulatory, gastroprotective, hepatoprotective, neuroprotective, and cardioprotective effects. In recent years, several of the biochemical, molecular, and cellular mechanisms of licorice and its active components have also been demonstrated in experimental studies. In this review, we summarized the new phytochemical, pharmacological, and toxicological data from recent experimental and clinical -
WO 2017/117099 Al 6 July 2017 (06.07.2017) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/117099 Al 6 July 2017 (06.07.2017) P O P C T (51) International Patent Classification: (US). GENESKY, Geoffery [FR/FR]; 14 Rue Royale, Λ 61Κ 8/04 (2006.01) A61K 8/97 (201 7.01) 75008 Paris (FR). A61K 8/06 (2006.01) A61K 31/70 (2006.01) (74) Agent: BALLS, R., James; Polsinelli PC, 1401 Eye A61K 8/34 (2006.01) A61K 31/351 (2006.01) Street, N.W., Suite 800, Washington, DC 20005 (US). A61K 8/60 (2006.01) A61K 31/355 (2006.01) A61K 5/67 (2006.01) A61K 31/7048 (2006.01) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (21) International Application Number: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, PCT/US20 16/068662 BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, (22) International Filing Date: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, 27 December 2016 (27. 12.2016) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, (25) Filing Language: English MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, (26) Publication Language: English NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, (30) Priority Data: TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, 62/272,326 29 December 201 5 (29. -
Chalcone Derivatives: Role in Anticancer Therapy
biomolecules Review Chalcone Derivatives: Role in Anticancer Therapy Yang Ouyang 1,† , Juanjuan Li 1,†, Xinyue Chen 1, Xiaoyu Fu 1, Si Sun 2,* and Qi Wu 1,* 1 Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China; [email protected] (Y.O.); [email protected] (J.L.); [email protected] (X.C.); [email protected] (X.F.) 2 Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, China * Correspondence: [email protected] (S.S.); [email protected] (Q.W.); Tel.: +86-15827099866 (S.S.); +86-13296588817 (Q.W.) † These authors contributed equally to this work. Abstract: Chalcones (1,3-diaryl-2-propen-1-ones) are precursors for flavonoids and isoflavonoids, which are common simple chemical scaffolds found in many naturally occurring compounds. Many chalcone derivatives were also prepared due to their convenient synthesis. Chalcones as weandhetic analogues have attracted much interest due to their broad biological activities with clinical potentials against various diseases, particularly for antitumor activity. The chalcone family has demonstrated potential in vitro and in vivo activity against cancers via multiple mechanisms, including cell cycle disruption, autophagy regulation, apoptosis induction, and immunomodulatory and inflammatory mediators. It represents a promising strategy to develop chalcones as novel anticancer agents. In addition, the combination of chalcones and other therapies is expected to be an effective way to improve anticancer therapeutic efficacy. However, despite the encouraging results for their response to cancers observed in clinical studies, a full description of toxicity is required for their clinical use as safe drugs for the treatment of cancer. -
Pharmacological Properties of Chalcones: a Review of Preclinical Including Molecular Mechanisms and Clinical Evidence
REVIEW published: 18 January 2021 doi: 10.3389/fphar.2020.592654 Pharmacological Properties of Chalcones: A Review of Preclinical Including Molecular Mechanisms and Clinical Evidence Bahare Salehi 1, Cristina Quispe 2, Imane Chamkhi 3,4, Nasreddine El Omari 5, Abdelaali Balahbib 6, Javad Sharifi-Rad 7,8*, Abdelhakim Bouyahya 9*, Muhammad Akram 10, Mehwish Iqbal 11, Anca Oana Docea 12, Constantin Caruntu 13,14*, Gerardo Leyva-Gómez 15, Abhijit Dey 16*, Miquel Martorell 17,18, Daniela Calina 19*, Víctor López 20,21 and Edited by: Francisco Les 20,21 Andrei Mocan, Iuliu Hat¸ieganu University of Medicine 1Medical Ethics and Law Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 2Facultad de Ciencias and Pharmacy, Romania de La Salud, Universidad Arturo Prat, Iquique, Chile, 3Faculty of Sciences, Mohammed V University of Rabat, Rabat, Morocco, Reviewed by: 4Laboratory of Plant-Microbe Interactions, AgroBioSciences, Mohammed VI Polytechnic University, Ben Guerir, Morocco, 5 Iulia Popescu, Laboratory of Histology, Embryology, and Cytogenetic, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, 6 University of Pittsburgh, United States Rabat, Morocco, Laboratory of Zoology and General Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, 7 8 Priyia Pusparajah, Morocco, Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Facultad de 9 Monash University Malaysia, Malaysia Medicina, Universidad del Azuay, Cuenca, Ecuador, Laboratory of Human Pathologies -
Dietary Chalcones with Chemopreventive and Chemotherapeutic Potential
Genes Nutr (2011) 6:125–147 DOI 10.1007/s12263-011-0210-5 RESEARCH PAPER Dietary chalcones with chemopreventive and chemotherapeutic potential Barbora Orlikova • Deniz Tasdemir • Frantisek Golais • Mario Dicato • Marc Diederich Received: 23 July 2010 / Accepted: 6 January 2011 / Published online: 4 February 2011 Ó Springer-Verlag 2011 Abstract Chalcones are absorbed in the daily diet and Introduction appear to be promising cancer chemopreventive agents. Chalcones represent an important group of the polyphenolic Polyphenols represent one of the most prevalent classes of family, which includes a large number of naturally occurring compounds found in our daily diet [171]. Over the last ten molecules. This family possesses an interesting spectrum of years, increasing attention has been dedicated to chalcones biological activities, including antioxidative, antibacterial, because of their interesting biological activities. Indeed, anti-inflammatory, anticancer, cytotoxic, and immuno- chalcones constitute an important group of natural com- suppressive potential. Compounds of this family have been pounds that are especially abundant in fruits (e.g., citruses, shown to interfere with each step of carcinogenesis, apples), vegetables (e.g., tomatoes, shallots, bean sprouts, including initiation, promotion and progression. Moreover, potatoes) and various plants and spices (e.g., licorice),— numerous compounds from the family of dietary chalcones many of which have been used for centuries in traditional appear to show activity against cancer cells, suggesting that herbal medicine [29]. Chemically, chalcones are open- these molecules or their derivatives may be considered as chain flavonoids bearing two aromatic rings linked by a potential anticancer drugs. This review will focus primarily three-carbon enone moiety (Fig. 1). -
Promising Anti-Inflammatory Effects of Chalcones Via Inhibition Of
Bioorganic Chemistry 87 (2019) 335–365 Contents lists available at ScienceDirect Bioorganic Chemistry journal homepage: www.elsevier.com/locate/bioorg Review article Promising anti-inflammatory effects of chalcones via inhibition of T cyclooxygenase, prostaglandin E2, inducible NO synthase and nuclear factor κb activities ⁎ Haroon ur Rashida,d, Yiming Xua, Nasir Ahmadc, Yaseen Muhammada, Lisheng Wanga,b, a School of Chemistry & Chemical Engineering, Guangxi University, 530004 Nanning, China b Medical College, Guangxi University, Nanning, China c Department of Chemistry, Islamia College University, Peshawar, Khyber Pakhtunkhwa, Pakistan d Department of Chemistry, Sarhad University of Science & Information Technology, 25000 Peshawar, Khyber Pakhtunkhwa, Pakistan ARTICLE INFO ABSTRACT Keywords: Chalcones (1, 3-Diphenyl-2-propen-1-one) consist of a three carbon α, β-unsaturated carbonyl system and act as Chalcone precursors for the biosynthesis of flavonoids in plants. However, laboratory synthesis of various chalcones has Inflammation also been reported. Both natural and synthetic chalcones are known to exhibit a variety of pharmacological Cyclooxygenase activities such as anti-inflammatory, antitumor, antibacterial, antifungal, antimalarial and antituberculosis. Inhibition These promising activities, ease of synthesis and simple chemical structure have awarded chalcones considerable Cardamonin attraction. This review focuses on the anti-inflammatory effects of chalcones, caused by their inhibitory action primarily against the activities and expressions of four key inflammatory mediators viz., cyclooxygenase, prostaglandin E2, inducible NO synthase, and nuclear factor κB. Various methodologies for the synthesis of chalcones have been discussed. The potency of recently synthesized chalcones is given in terms of their IC50 values. Structure-Activity Relationships (SARs) of a variety of chalcone derivatives have been discussed.