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Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (15 January 2019) | Viewed by 56072

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Special Issue Editors

Dr. Maria Emília De Sousa

E-Mail Website1 Website2
Guest Editor

1. Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), 4450-208 Porto, Portugal
2. Laboratory of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
Interests: medicinal chemistry; organic synthesis; heterocycles; P-glycoprotein; anticancer; antimicrobials; chiral drugs; marine natural products
Special Issues, Collections and Topics in MDPI journals

Dr. Honorina Cidade

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Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira n° 228, 4050-313 Porto, Portugal
Interests: medicinal chemistry; organic synthesis; drug discovery; anticancer activity; antimicrobial activity; chiral drugs; natural products
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Carlos Manuel Afonso

E-Mail Website
Guest Editor

1. Laboratório de Química Orgânica e Farmacêutica, Dep. Ciências Químicas, Faculdade de Farmácia da Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
2. CIIMAR: Centro Interdisciplinar de Investigação Marinha e Ambiental da Universidade do Porto, Rua dos Bragas, 289, 4050-123 Porto, Portugal
Interests: medicinal chemistry; organic synthesis; pharmaceutical analysis; ADMET prediction; natural products
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is dedicated to Prof. Madalena Pinto (http://www.madalenapinto.com), who is currently Full Professor at the Department of Chemistry, Faculty of Pharmacy at the University of Porto (FFUP), on the occasion of her 70^th birthday (to be celebrated on 15 September, 2018), and in honor of her many achievements in Medicinal Chemistry, and, particularly, her outstanding research contributions in the fields concerning “Xanthones”.

Xanthones are a class of oxygenated heterocyclic compounds with a dibenzo-γ-pyrone scaffold which have long been recognized for their wide range of biological and pharmacological activities.

Professor Madalena Pinto is undoubtedly one of the leading Medicinal Chemists in Portugal and a well-known personality in the scientific community. She graduated in the Faculty of Pharmacy at the University of Porto, and carried out her doctoral studies in the University of São Paulo, Brazil, with Professor Otto Gottlieb (nominated for the Nobel Prize in Chemistry in 1999). She was the Coordinator of meaningful Portuguese Research Centers, such as CEQOFFUP-FCT- R&D 226 (from 1996 to 2007) and “Center of Medicinal Chemistry of the University of Porto” (CEQUIMED- UP, FCT I&D 4040, from 2007–2015). Professor Madalena Pinto was the only woman as Director (1982–1984) of the Faculty of Pharmacy of the University of Porto so far. She also created the First Course of Pharmaceutical Sciences of the Instituto Superior das Ciências da Saúde-Norte (CESPU) and was the Director of the first PhD Course in Pharmaceutical Sciences of FFUP (2009/2010) and Member of the Committee of Therapeutic Chemistry of the Portuguese Society of Chemistry (2012–2015). Currently, she is Team Leader of the Group of Natural Products and Medicinal Chemistry at Interdisciplinary Centre of Marine and Environmental Research (CIIMAR) (2014-). Professor Madalena Pinto has been the head of the Laboratory of Organic and Pharmaceutical Chemistry of the FFUP since 1985 and is Director of the first Master Course in Pharmaceutical Chemistry of FFUP. She is also Adjunct Professor of Kasetsart University. Bangkok, Thailand. Professor Madalena Pinto is the author of more than two hundred publications, with more than 3200 citations, and an h-index of 30. Her research interests embrace broad areas such as Natural Products and Medicinal Chemistry as well as more specific related with organic synthesis, chirality, and analytic applications of molecular recognition. In her outstanding research, Professor Madalena Pinto has contributed significantly for revealing diverse aspects of chemistry and biological activities of a large number of xanthone derivatives, combining successfully organic synthesis with principles of natural products.

Professor Madalena Pinto supervised a large number of postgraduate and post-doctoral students, many of whom are currently holding academic positions in Portugal and around the world. During almost 50 years of Professorship she has been truly dedicated to teaching Chemistry at all levels, being the author of several pedagogical publications in the field of Medicinal Chemistry.

On behalf of many colleagues, students and collaborators, we are honored to dedicate this Special Issue to Madalena Pinto, and wish Professor Madalena good health, much energy and further success in her scientific life and hope for lasting cooperation in Medicinal Chemistry research and education.

Prof. Dr. Maria Emília de Sousa
Dr. Honorina Cidade
Prof. Dr. Carlos Manuel Afonso
Guest Editors

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Keywords

xanthones
natural products
chirality
O-heterocycles

Published Papers (12 papers)

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Research

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27 pages, 4813 KiB

Open AccessFeature PaperArticle

Newly Synthesized Oxygenated Xanthones as Potential P-Glycoprotein Activators: In Vitro, Ex Vivo, and In Silico Studies

by Eva Martins, Vera Silva, Agostinho Lemos, Andreia Palmeira, Ploenthip Puthongking, Emília Sousa, Carolina Rocha-Pereira, Carolina I. Ghanem, Helena Carmo, Fernando Remião and Renata Silva

Molecules 2019, 24(4), 707; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24040707 - 15 Feb 2019

Cited by 23 | Viewed by 5179

Abstract

P-glycoprotein (P-gp) plays a crucial role in the protection of susceptible organs, by significantly decreasing the absorption/distribution of harmful xenobiotics and, consequently, their toxicity. Therefore, P-gp has been proposed as a potential antidotal pathway, when activated and/or induced. Knowing that xanthones are known to interact with P-gp, the main goal was to study P-gp induction or/and activation by six new oxygenated xanthones (OX 1-6). Furthermore, the potential protection of Caco-2 cells against paraquat cytotoxicity was also assessed. The most promising compound was further tested for its ability to increase P-gp activity ex vivo, using everted intestinal sacs from adult Wistar-Han rats. The oxygenated xanthones interacted with P-gp in vitro, increasing P-gp expression and/or activity 24 h after exposure. Additionally, after a short-incubation period, several xanthones were identified as P-gp activators, as they immediately increased P-gp activity. Moreover, some xanthones decreased PQ cytotoxicity towards Caco-2 cells, an effect prevented under P-gp inhibition. Ex vivo, a significant increase in P-gp activity was observed in the presence of OX6, which was selectively blocked by a model P-gp inhibitor, zosuquidar, confirming the in vitro results. Docking simulations between a validated P-gp model and the tested xanthones predicted these interactions, and these compounds also fitted onto previously described P-gp induction and activation pharmacophores. In conclusion, the in vitro, ex vivo, and in silico results suggest the potential of some of the oxygenated xanthones in the modulation of P-gp, disclosing new perspectives in the therapeutics of intoxications by P-gp substrates. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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14 pages, 3419 KiB

Open AccessFeature PaperArticle

Licofelone-DPPC Interactions: Putting Membrane Lipids on the Radar of Drug Development

by Catarina Pereira-Leite, Daniela Lopes-de-Campos, Philippe Fontaine, Iolanda M. Cuccovia, Cláudia Nunes and Salette Reis

Molecules 2019, 24(3), 516; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24030516 - 31 Jan 2019

Cited by 11 | Viewed by 3937

Abstract

(1) Background: Membrane lipids have been disregarded in drug development throughout the years. Recently, they gained attention in drug design as targets, but they are still disregarded in the latter stages. Thus, this study aims to highlight the relevance of considering membrane lipids in the preclinical phase of drug development. (2) Methods: The interactions of a drug candidate for clinical use (licofelone) with a membrane model system made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were evaluated by combining Langmuir isotherms, Brewster angle microscopy (BAM), polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), and grazing-incidence X-ray diffraction (GIXD) measurements. (3) Results: Licofelone caused the expansion of the DPPC isotherm without changing the lipid phase transition profile. Moreover, licofelone induced the reduction of DPPC packing density, while increasing the local order of the DPPC acyl chains. (4) Conclusions: The licofelone-induced alterations in the structural organization of phosphatidylcholine monolayers may be related to its pharmacological actions. Thus, the combination of studying drug-membrane interactions with the pharmacological characterization that occurs in the preclinical stage may gather additional information about the mechanisms of action and toxicity of drug candidates. Ultimately, the addition of this innovative step shall improve the success rate of drug development. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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17 pages, 3423 KiB

Open AccessFeature PaperArticle

Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations

by Ana Alves, Marta Correia-da-Silva, Claúdia Nunes, João Campos, Emília Sousa, Patrícia M.A. Silva, Hassan Bousbaa, Francisca Rodrigues, Domingos Ferreira, Paulo C. Costa and Madalena Pinto

Molecules 2019, 24(3), 409; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24030409 - 23 Jan 2019

Cited by 14 | Viewed by 5542

Abstract

Following our previous work on the antitumor activity of acetylated flavonosides, a new acetylated xanthonoside, 3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone (2), was synthesized and discovered as a potent inhibitor of tumor cell growth. The synthesis involved the glycosylation of 3,6-di-hydroxyxanthone (1) with acetobromo-α-d-glucose. Glycosylation with silver carbonate decreased the amount of glucose donor needed, comparative to the biphasic glycosylation. Xanthone 2 showed a potent anti-growth activity, with GI₅₀ < 1 μM, in human cell lines of breast, lung, and glioblastoma cancers. Current treatment for invasive brain glioma is still inadequate and new agents against glioblastoma with high brain permeability are urgently needed. To overcome these issues, xanthone 2 was encapsulated in a liposome. To increase the well-known low stability of these drug carriers, a proliposome formulation was developed using the spray drying method. Both formulations were characterized and compared regarding three months stability and in vitro anti-growth activity. While the proliposome formulation showed significantly higher stability, it was at the expense of losing its biocompatibility as a drug carrier in higher concentrations. More importantly, the new xanthone 2 was still able to inhibit the growth of glioblastoma cells after liposome formulation. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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19 pages, 3216 KiB

Open AccessArticle

New Alkoxy Flavone Derivatives Targeting Caspases: Synthesis and Antitumor Activity Evaluation

by Joana Moreira, Diana Ribeiro, Patrícia M. A. Silva, Nair Nazareth, Madalena Monteiro, Andreia Palmeira, Lucília Saraiva, Madalena Pinto, Hassan Bousbaa and Honorina Cidade

Molecules 2019, 24(1), 129; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24010129 - 31 Dec 2018

Cited by 15 | Viewed by 4687

Abstract

The antitumor activity of natural flavonoids has been exhaustively reported. Previously it has been demonstrated that prenylation of flavonoids allows the discovery of new compounds with improved antitumor activity through the activation of caspase-7 activity. The synthesis of twenty-five flavonoids (4–28) with one or more alkyl side chains was carried out. The synthetic approach was based on the reaction with alkyl halide in alkaline medium by microwave (MW) irradiation. The in vitro cell growth inhibitory activity of synthesized compounds was investigated in three human tumor cell lines. Among the tested compounds, derivatives 6, 7, 9, 11, 13, 15, 17, and 18 revealed potent growth inhibitory activity (GI₅₀ < 10 μM), being the growth inhibitory effect of compound 13 related with a pronounced caspase-7 activation on MCF-7 breast cancer cells and yeasts expressing human caspase-7. A quantitative structure-activity relationship (QSAR) model predicted that hydrophilicity, pattern of ring substitution/shape, and presence of partial negative charged atoms were the descriptors implied in the growth inhibitory effect of synthesized compounds. Docking studies on procaspase-7 allowed predicting the binding of compound 13 to the allosteric site of procaspase-7. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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19 pages, 4045 KiB

Open AccessArticle

The Antitumor Activity of a Lead Thioxanthone is Associated with Alterations in Cholesterol Localization

by Raquel T. Lima, Diana Sousa, Ana Sara Gomes, Nuno Mendes, Rune Matthiesen, Madalena Pedro, Franklim Marques, Madalena M. Pinto, Emília Sousa and M. Helena Vasconcelos

Molecules 2018, 23(12), 3301; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23123301 - 12 Dec 2018

Cited by 12 | Viewed by 3553

Abstract

The search for novel anticancer small molecules and strategies remains a challenge. Our previous studies have identified TXA1 (1-{[2-(diethylamino)ethyl]amino}-4-propoxy-9H- thioxanthen-9-one) as a hit compound, with in vitro antitumor potential by modulating autophagy and apoptosis in human tumor cell lines. In the present study, the mechanism of action and antitumor potential of the soluble salt of this molecule (TXA1.HCl) was further investigated using in vitro and mouse xenograft tumor models of NSCLC. Our results showed that TXA1.HCl affected steroid biosynthesis, increased RagD expression, and caused abnormal cellular cholesterol localization. In addition, TXA1.HCl treatment presented no toxicity to nude mice and significantly reduced the growth of human NSCLC cells xenografts in mice. Overall, this work provides new insights into the mechanism of action of TXA1, which may be relevant for the development of anticancer therapeutic strategies, which target cholesterol transport. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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14 pages, 986 KiB

Open AccessFeature PaperArticle

Cardiovascular Profile of Xanthone-Based 1,4 Dihydropyridines Bearing a Lidoflazine Pharmacophore Fragment

by Alessandra Bisi, Matteo Micucci, Silvia Gobbi, Federica Belluti, Roberta Budriesi and Angela Rampa

Molecules 2018, 23(12), 3088; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23123088 - 27 Nov 2018

Cited by 4 | Viewed by 2965

Abstract

As a follow-up to our previous studies on differently substituted 1,4-dihydropyridines endowed with a peculiar cardiac selectivity, in this paper, a small series of hybrid compounds bearing the pharmacophore fragment of lidoflazine in position 2 or 3 on a 4-(xanthen-9-one)-dihydropyridine core was reported. Lidoflazine was selected due to our promising previously reported data, and the xanthen-9-one substituent was introduced in position 4 of the dihydropyridine scaffold based on the cardiac selectivity observed in several of our studies. The new hybrid compounds were tested to assess cardiac and vascular activities, and the data were evaluated in comparison with those previously obtained for 4-(xanthen-9-one)-dihydropyridines and lidoflazine–nifedipine hybrid compounds. The functional studies indicated an interesting peculiar selectivity for the cardiac parameter inotropy, in particular when the lidoflazine fragment was introduced in position 2 of the dihydropyridine scaffold (4a–e), and thus a possible preferential binding with the Ca_v 1.2 isoform of l-type calcium channels, which are mainly involved in cardiac contractility. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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11 pages, 8293 KiB

Open AccessArticle

Influence of Hydroxyl Functional Group on the Structure and Stability of Xanthone: A Computational Approach

by Vera L. S. Freitas and Maria D. M. C. Ribeiro da Silva

Molecules 2018, 23(11), 2962; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23112962 - 13 Nov 2018

Cited by 4 | Viewed by 3036

Abstract

The present work addresses computational research focused on the energetic and structural properties of four isomers monohydroxyxanthone, using the G3(MP2)//B3LYP method, in order to evaluate the influence of the hydroxyl (—OH moiety) functional group on the xanthone molecule. The combination of these computational results with previous experimental data of these compounds enabled the determination of their enthalpies, entropies and Gibbs energies of formation, in the gaseous phase, and consequently to infer about the relative thermodynamic stability of the four isomers. Other issues were also addressed for the hydroxyxanthone isomers, namely the conformational and the tautomeric equilibrium analysis of the optimized molecular structures, the frontier orbitals, and the electrostatic potential energy maps. Complementarily, an energetic study of the intramolecular

O — H \dots O

hydrogen bond for 1-hydroxanthone was also performed. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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16 pages, 1271 KiB

Open AccessArticle

Lichen Xanthones as Models for New Antifungal Agents

by Diana I. S. P. Resende, Patrícia Pereira-Terra, Ângela S. Inácio, Paulo Martins da Costa, Eugénia Pinto, Emília Sousa and Madalena M. M. Pinto

Molecules 2018, 23(10), 2617; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23102617 - 12 Oct 2018

Cited by 24 | Viewed by 4117

Abstract

Due to the emergence of multidrug-resistant pathogenic microorganisms, the search for new antimicrobial compounds plays an important role in current medicinal chemistry research. Inspired by lichen antimicrobial xanthones, a series of novel chlorinated xanthones was prepared using five chlorination methods (Methods A–E) to obtain different patterns of substitution in the xanthone scaffold. All the synthesized compounds were evaluated for their antimicrobial activity. Among them, 3-chloro-4,6-dimethoxy-1-methyl-9H-xanthen-9-one 15 showed promising antibacterial activity against E. faecalis (ATCC 29212 and 29213) and S. aureus ATCC 29213. 2,7-Dichloro-3,4,6-trimethoxy-1-methyl-9H-xanthen-9-one 18 revealed a potent fungistatic and fungicidal activity against dermatophytes clinical strains (T. rubrum, M. canis, and E. floccosum (MIC = 4–8 µg/mL)). Moreover, when evaluated for its synergistic effect for T. rubrum, compound 18 exhibited synergy with fluconazole (ΣFIC = 0.289). These results disclosed new hit xanthones for both antibacterial and antifungal activity. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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15 pages, 5770 KiB

Open AccessCommunication

The Design and Synthesis of N-Xanthone Benzenesulfonamides as Novel Phosphoglycerate Mutase 1 (PGAM1) Inhibitors

by Penghui Wang, Lulu Jiang, Yang Cao, Deyong Ye and Lu Zhou

Molecules 2018, 23(6), 1396; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules23061396 - 08 Jun 2018

Cited by 9 | Viewed by 4050

Abstract

Upregulation of phosphoglycerate mutase 1 (PGAM1) has been identified as one common phenomenon in a variety of cancers. Inhibition of PGAM1 provides a new promising therapeutic strategy for cancer treatment. Herein, based on our previous work, a series of new N-xanthone benzenesulfonamides were discovered as novel PGAM1 inhibitors. The representative molecule 15h, with an IC₅₀ of 2.1 μM, showed an enhanced PGAM1 inhibitory activity and higher enzyme inhibitory specificity compared to PGMI-004A, as well as a slightly improved antiproliferative activity. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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Review

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29 pages, 21836 KiB

Open AccessFeature PaperReview

Chiral Derivatives of Xanthones with Antimicrobial Activity

by Joana Araújo, Carla Fernandes, Madalena Pinto and Maria Elizabeth Tiritan

Molecules 2019, 24(2), 314; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24020314 - 16 Jan 2019

Cited by 36 | Viewed by 5418

Abstract

According to the World Health Organization, the exacerbated use of antibiotics worldwide is increasing multi-resistant infections, especially in the last decade. Xanthones are a class of compounds receiving great interest in drug discovery and development that can be found as natural products or obtained by synthesis. Many derivatives of xanthones are chiral and associated with relevant biological activities, including antimicrobial. The aim of this review is to compile information about chiral derivatives of xanthones from natural sources and their synthesized examples with antimicrobial activity. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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23 pages, 3128 KiB

Open AccessFeature PaperReview

Structures, Activities and Drug-Likeness of Anti-Infective Xanthone Derivatives Isolated from the Marine Environment: A Review

by Daniela R. P. Loureiro, José X. Soares, Joana C. Costa, Álvaro F. Magalhães, Carlos M. G. Azevedo, Madalena M. M. Pinto and Carlos M. M. Afonso

Molecules 2019, 24(2), 243; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24020243 - 10 Jan 2019

Cited by 40 | Viewed by 6863

Abstract

Marine organisms represent almost half of total biodiversity and are a very important source of new bioactive substances. Within the varied biological activities found in marine products, their antimicrobial activity is one of the most relevant. Infectious diseases are responsible for high levels of morbidity and mortality and many antimicrobials lose their effectiveness with time due to the development of resistance. These facts justify the high importance of finding new, effective and safe anti-infective agents. Among the variety of biological activities of marine xanthone derivatives, one that must be highlighted is their anti-infective properties. In this work, a literature review of marine xanthones with anti-infective activity, namely antibacterial, antifungal, antiparasitic and antiviral, is presented. Their structures, biological activity, sources and the methods used for bioactivity evaluation are described. The xanthone derivatives are grouped in three sets: xanthones, hydroxanthones and glycosylated derivatives. Moreover, molecular descriptors, biophysico-chemical properties, and pharmacokinetic parameters were calculated, and the chemical space occupied by marine xanthone derivatives is recognized. The chemical space was compared with marketed drugs and framed accordingly to the drug-likeness concept in order to profile the pharmacokinetic of anti-infective marine xanthone derivatives. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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33 pages, 3439 KiB

Open AccessFeature PaperReview

Carboxyxanthones: Bioactive Agents and Molecular Scaffold for Synthesis of Analogues and Derivatives

by João Ribeiro, Cláudia Veloso, Carla Fernandes, Maria Elizabeth Tiritan and Madalena M. M. Pinto

Molecules 2019, 24(1), 180; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24010180 - 05 Jan 2019

Cited by 17 | Viewed by 5100

Abstract

Xanthones represent a structurally diverse group of compounds with a broad range of biological and pharmacological activities, depending on the nature and position of various substituents in the dibenzo-γ-pyrone scaffold. Among the large number of natural and synthetic xanthone derivatives, carboxyxanthones are very interesting bioactive compounds as well as important chemical substrates for molecular modifications to obtain new derivatives. A remarkable example is 5,6-dimethylxanthone-4-acetic acid (DMXAA), a simple carboxyxanthone derivative, originally developed as an anti-tumor agent and the first of its class to enter phase III clinical trials. From DMXAA new bioactive analogues and derivatives were also described. In this review, a literature survey covering the report on carboxyxanthone derivatives is presented, emphasizing their biological activities as well as their application as suitable building blocks to obtain new bioactive derivatives. The data assembled in this review intends to highlight the therapeutic potential of carboxyxanthone derivatives and guide the design for new bioactive xanthone derivatives. Full article

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

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