Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.6
4.9
Journals
Marine Drugs
Special Issues
From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to...
share announcement

From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012)

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (31 October 2018) | Viewed by 73467

Special Issue Editors

Prof. Dr. Patrizia Ciminiello

E-Mail Website
Guest Editor
Dipartimento di Chimica delle Sostanze Naturali, Università di Napoli "Federico II", Via D. Montesano 49, I-80131 Napoli, Italy
Interests: marine natural products; marine plankton; structure elucidation; marine biotoxins; dinoflagellates
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Alfonso Mangoni

E-Mail
Guest Editor
Department of Pharmacy, University of Naples Federico II, Naples, Italy
Interests: marine natural products; structural elucidation; biosynthetic gene clusters; metagenomics; computational chemistry
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Marialuisa Menna

E-Mail Website
Guest Editor
Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano, 49 – 80131, Naples, Italy
Interests: natural products chemistry; NMR spectroscopy; small molecules structure elucidation; bioactive marine metabolites; synthetic and medicinal chemistry; chemical libraries; marine-inspired leads to drugs
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Orazio Taglialatela-Scafati

E-Mail Website1 Website2
Guest Editor
Department of Pharmacy, University of Naples Federico II, Naples, Italy
Interests: marine and terrestrial natural products; pharmaceutical biology; stereostructure elucidation; bioactivity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Marine Drugs and Molecules are pleased to announce a joint commemorative Special Issue dedicated to Professor Ernesto Fattorusso, on the occasion of his 80th birthday in 2017, for his outstanding contribution in the research field of bioactive natural products.

Prof. Fattorusso (born in 1937) has been Professor of Organic Chemistry at the University of Naples Federico II since 1975. He was one of the founding fathers of the chemistry of marine natural products, and, more recently, he was also involved in the investigation of therapeutically active terrestrial plants of the Mediterranean flora. His prolific scientific activity is documented by more than 350 papers describing the isolation and identification of bioactive natural products, potential leads for drug, cosmetic, and biotechnological applications. Prof. Fattorusso founded a multidisciplinary research group, the NeaNat group, based at the Department of Pharmacy of the University of Naples Federico II, which will be continuing to work on these topics.

Since 1980, Prof. Fattorusso has coordinated many national and international projects (NOMATEC, BIOTOXmarin, NatPharma, BLUEGENICS among others) and established fruitful collaborations with several institutions around the world. Prof. Fattorusso has received a remarkable number of awards, including the prestigious Paul Scheuer Award in 2010 for his studies in the field of marine natural products: he was the first European scientist to receive this award.

This commemorative issue welcomes submission of previously unpublished manuscripts (original researches or reviews) on the investigation of biologically active chemical entities, with particular regard to natural products isolated from plants, marine invertebrates and microorganisms, potentially useful as lead compounds for the development of new drugs or biological tools.

We plan to receive submissions from November 2016 to the end of September 2017. Manuscripts will be published on an ongoing basis after being processed.

Prof. Dr. Patrizia Ciminiello
Prof. Dr. Alfonso Mangoni
Prof. Dr. Marialuisa Menna
Prof. Dr. Orazio Taglialatela-Scafati
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Lead compounds
  • Natural products
  • Biological tools
  • Drug development
  • Structure elucidation-
  • Organic synthesis

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Related Special Issue

Published Papers (10 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

16 pages, 7375 KiB  
Article
Fishing for Targets of Alien Metabolites: A Novel Peroxisome Proliferator-Activated Receptor (PPAR) Agonist from a Marine Pest
by Rosa Maria Vitale, Enrico D'Aniello, Stefania Gorbi, Andrea Martella, Cristoforo Silvestri, Maria Elisa Giuliani, Tariq Fellous, Alessandra Gentile, Marianna Carbone, Adele Cutignano, Laura Grauso, Laura Magliozzi, Gianluca Polese, Biagio D'Aniello, Fanny Defranoux, Serena Felline, Antonio Terlizzi, Antonio Calignano, Francesco Regoli, Vincenzo Di Marzo, Pietro Amodeo and Ernesto Molloadd Show full author list remove Hide full author list
Mar. Drugs 2018, 16(11), 431; https://doi.org/10.3390/md16110431 - 3 Nov 2018
Cited by 27 | Viewed by 7144
Abstract
Although the chemical warfare between invasive and native species has become a central problem in invasion biology, the molecular mechanisms by which bioactive metabolites from invasive pests influence local communities remain poorly characterized. This study demonstrates that the alkaloid caulerpin (CAU)—a bioactive component [...] Read more.
Although the chemical warfare between invasive and native species has become a central problem in invasion biology, the molecular mechanisms by which bioactive metabolites from invasive pests influence local communities remain poorly characterized. This study demonstrates that the alkaloid caulerpin (CAU)—a bioactive component of the green alga Caulerpa cylindracea that has invaded the entire Mediterranean basin—is an agonist of peroxisome proliferator-activated receptors (PPARs). Our interdisciplinary study started with the in silico prediction of the ligand-protein interaction, which was then validated by in vivo, ex vivo and in vitro assays. On the basis of these results, we candidate CAU as a causal factor of the metabolic and behavioural disorders observed in Diplodus sargus, a native edible fish of high ecological and commercial relevance, feeding on C. cylindracea. Moreover, given the considerable interest in PPAR activators for the treatment of relevant human diseases, our findings are also discussed in terms of a possible nutraceutical/pharmacological valorisation of the invasive algal biomasses, supporting an innovative strategy for conserving biodiversity as an alternative to unrealistic campaigns for the eradication of invasive pests. Full article
(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))
►▼ Show Figures

Graphical abstract

19 pages, 2150 KiB  
Article
Chemical Reactivity Properties, pKa Values, AGEs Inhibitor Abilities and Bioactivity Scores of the Mirabamides A–H Peptides of Marine Origin Studied by Means of Conceptual DFT
by Juan Frau, Norma Flores-Holguín and Daniel Glossman-Mitnik
Mar. Drugs 2018, 16(9), 302; https://doi.org/10.3390/md16090302 - 28 Aug 2018
Cited by 42 | Viewed by 5313
Abstract
The MN12SX density functional, in connection with the Def2TZVP basis set, was assessed, together with the SMD solvation model (Solvation Model based on the Density), for calculation of the molecular properties and structure of a group of peptides of marine origin named Mirabamides [...] Read more.
The MN12SX density functional, in connection with the Def2TZVP basis set, was assessed, together with the SMD solvation model (Solvation Model based on the Density), for calculation of the molecular properties and structure of a group of peptides of marine origin named Mirabamides A–H. All the chemical reactivity descriptors for the systems were calculated via Conceptual Density Functional Theory (CDFT). The active sites suitable for nucleophilic, electrophilic, and radical attacks were chosen by linking them with the Fukui function indices, nucleophilic and electrophilic Parr functions, and condensed Dual Descriptor Δ f ( r ) , respectively. Additionally, the p K a values for the different peptides are predicted with great accuracy as well as the ability of the studied molecule in acting as an efficient inhibitor of the formation of Advanced Glycation Endproducts (AGEs), which constitutes a useful knowledge for the development of drugs for fighting Diabetes, Alzheimer and Parkinson diseases. Finally, the bioactivity scores for the Mirabamides A–H are predicted through different methodologies. Full article
(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))
►▼ Show Figures

Figure 1

16 pages, 3261 KiB  
Article
Total Synthesis of Pulmonarin B and Design of Brominated Phenylacetic Acid/Tacrine Hybrids: Marine Pharmacophore Inspired Discovery of New ChE and Aβ Aggregation Inhibitors
by Zhi-Qiang Cheng, Jia-Li Song, Kongkai Zhu, Juan Zhang, Cheng-Shi Jiang and Hua Zhang
Mar. Drugs 2018, 16(9), 293; https://doi.org/10.3390/md16090293 - 21 Aug 2018
Cited by 19 | Viewed by 4929
Abstract
A marine natural product, pulmonarin B (1), and a series of related tacrine hybrid analogues were synthesized and evaluated as cholinesterase (ChE) inhibitors. The in vitro ChE assay results revealed that 1 showed moderate dual acetylcholinesterase (AChE)/ butyrylcholinesterase (BChE) inhibitory activity, [...] Read more.
A marine natural product, pulmonarin B (1), and a series of related tacrine hybrid analogues were synthesized and evaluated as cholinesterase (ChE) inhibitors. The in vitro ChE assay results revealed that 1 showed moderate dual acetylcholinesterase (AChE)/ butyrylcholinesterase (BChE) inhibitory activity, while the hybrid 12j proved to be the most potent dual inhibitor among the designed derivatives, being almost as active as tacrine. Molecular modeling studies together with kinetic analysis suggested that 12j interacted with both the catalytic active site and peripheral anionic site of AChE. Compounds 1 and 12j could also inhibit self-induced and AChE-induced Aβ aggregation. In addition, the cell-based assay against the human hepatoma cell line (HepG2) revealed that 1 and 12j did not show significant hepatotoxicity compared with tacrine and donepezil. Taken together, the present study confirmed that compound 1 was a potential anti-Alzheimer’s disease (AD) hit, and 12j could be highlighted as a multifunctional lead compound for anti-AD drug development. Full article
(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))
►▼ Show Figures

Graphical abstract

15 pages, 2737 KiB  
Article
Bioactive Compounds from Posidonia oceanica (L.) Delile Impair Malignant Cell Migration through Autophagy Modulation
by Manuela Leri, Matteo Ramazzotti, Marzia Vasarri, Sara Peri, Emanuela Barletta, Carlo Pretti and Donatella Degl’Innocenti
Mar. Drugs 2018, 16(4), 137; https://doi.org/10.3390/md16040137 - 21 Apr 2018
Cited by 29 | Viewed by 5990
Abstract
Posidonia oceanica (L.) Delile is a marine plant with interesting biological properties potentially ascribed to the synergistic combination of bioactive compounds. Our previously described extract, obtained from the leaves of P. oceanica, showed the ability to impair HT1080 cell migration by targeting [...] Read more.
Posidonia oceanica (L.) Delile is a marine plant with interesting biological properties potentially ascribed to the synergistic combination of bioactive compounds. Our previously described extract, obtained from the leaves of P. oceanica, showed the ability to impair HT1080 cell migration by targeting both expression and activity of gelatinases. Commonly, the lack of knowledge about the mechanism of action of phytocomplexes may be an obstacle regarding their therapeutic use and development. The aim of this study was to gain insight into the molecular signaling through which such bioactive compounds impact on malignant cell migration and gelatinolytic activity. The increase in autophagic vacuoles detected by confocal microscopy suggested an enhancement of autophagy in a time and dose dependent manner. This autophagy activation was further confirmed by monitoring pivotal markers of autophagy signaling as well as by evidencing an increase in IGF-1R accumulation on cell membranes. Taken together, our results confirm that the P. oceanica phytocomplex is a promising reservoir of potent and cell safe molecules able to defend against malignancies and other diseases in which gelatinases play a major role in progression. In conclusion, the attractive properties of this phytocomplex may be of industrial interest in regard to the development of novel health-promoting and pharmacological products for the treatment or prevention of several diseases. Full article
(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))
►▼ Show Figures

Figure 1

14 pages, 4731 KiB  
Article
Function-Oriented Synthesis of Marine Phidianidine Derivatives as Potential PTP1B Inhibitors with Specific Selectivity
by Jin Liu, Yu Chen, Jing-Ya Li, Cheng Luo, Jia Li, Kai-Xian Chen, Xu-Wen Li and Yue-Wei Guo
Mar. Drugs 2018, 16(3), 97; https://doi.org/10.3390/md16030097 - 20 Mar 2018
Cited by 22 | Viewed by 5662
Abstract
Phidianidines A and B are two novel marine indole alkaloids bearing an uncommon 1,2,4-oxadiazole ring and exhibiting various biological activities. Our previous research showed that the synthesized phidianidine analogs had the potential to inhibit the activity of protein tyrosine phosphatase 1B (PTP1B), a [...] Read more.
Phidianidines A and B are two novel marine indole alkaloids bearing an uncommon 1,2,4-oxadiazole ring and exhibiting various biological activities. Our previous research showed that the synthesized phidianidine analogs had the potential to inhibit the activity of protein tyrosine phosphatase 1B (PTP1B), a validated target for Type II diabetes, which indicates that these analogs are worth further structural modification. Therefore, in this paper, a series of phidianidine derivatives were designed and rapidly synthesized with a function-oriented synthesis (FOS) strategy. Their inhibitory effects on PTP1B and T-cell protein tyrosine phosphatase (TCPTP) were evaluated, and several compounds displayed significant inhibitory potency and specific selectivity over PTP1B. The structure–activity relationship (SAR) and molecular docking analyses are also described. Full article
(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))
►▼ Show Figures

Figure 1

2951 KiB  
Article
Insight into the Mechanism of Action of Marine Cytotoxic Thiazinoquinones
by Concetta Imperatore, Paola Cimino, Gerardo Cebrián-Torrejón, Marco Persico, Anna Aiello, Maria Senese, Caterina Fattorusso, Marialuisa Menna and Antonio Doménech-Carbó
Mar. Drugs 2017, 15(11), 335; https://doi.org/10.3390/md15110335 - 2 Nov 2017
Cited by 11 | Viewed by 4352
Abstract
The electrochemical response of four natural cytotoxic thiazinoquinones isolated from the Aplidium species was studied using conventional solution-phase and solid-state techniques, based on the voltammetry of immobilized particles methodology. The interaction with O2 and electrochemically generated reactive oxygen species (ROS) was electrochemically [...] Read more.
The electrochemical response of four natural cytotoxic thiazinoquinones isolated from the Aplidium species was studied using conventional solution-phase and solid-state techniques, based on the voltammetry of immobilized particles methodology. The interaction with O2 and electrochemically generated reactive oxygen species (ROS) was electrochemically monitored. At the same time, a molecular modeling study including density functional theory (DFT) calculations was performed in order to analyze the conformational and electronic properties of the natural thiazinoquinones, as well as those of their reduced intermediates. The obtained electrochemical and computational results were analyzed and correlated to cytotoxic activity of these compounds, highlighting some features possibly related to their mechanism of action. Full article
(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

37 pages, 5103 KiB  
Review
Clogging the Ubiquitin-Proteasome Machinery with Marine Natural Products: Last Decade Update
by Gerardo Della Sala, Francesca Agriesti, Carmela Mazzoccoli, Tiziana Tataranni, Valeria Costantino and Claudia Piccoli
Mar. Drugs 2018, 16(12), 467; https://doi.org/10.3390/md16120467 - 26 Nov 2018
Cited by 21 | Viewed by 5472
Abstract
The ubiquitin-proteasome pathway (UPP) is the central protein degradation system in eukaryotic cells, playing a key role in homeostasis maintenance, through proteolysis of regulatory and misfolded (potentially harmful) proteins. As cancer cells produce proteins inducing cell proliferation and inhibiting cell death pathways, UPP [...] Read more.
The ubiquitin-proteasome pathway (UPP) is the central protein degradation system in eukaryotic cells, playing a key role in homeostasis maintenance, through proteolysis of regulatory and misfolded (potentially harmful) proteins. As cancer cells produce proteins inducing cell proliferation and inhibiting cell death pathways, UPP inhibition has been exploited as an anticancer strategy to shift the balance between protein synthesis and degradation towards cell death. Over the last few years, marine invertebrates and microorganisms have shown to be an unexhaustive factory of secondary metabolites targeting the UPP. These chemically intriguing compounds can inspire clinical development of novel antitumor drugs to cope with the incessant outbreak of side effects and resistance mechanisms induced by currently approved proteasome inhibitors (e.g., bortezomib). In this review, we report about (a) the role of the UPP in anticancer therapy, (b) chemical and biological properties of UPP inhibitors from marine sources discovered in the last decade, (c) high-throughput screening techniques for mining natural UPP inhibitors in organic extracts. Moreover, we will tell about the fascinating story of salinosporamide A, the first marine natural product to access clinical trials as a proteasome inhibitor for cancer treatment. Full article
(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))
►▼ Show Figures

Graphical abstract

3238 KiB  
Review
Structural Diversity, Biological Properties and Applications of Natural Products from Cyanobacteria. A Review
by Sayed Asmat Ali Shah, Najeeb Akhter, Bibi Nazia Auckloo, Ishrat Khan, Yanbin Lu, Kuiwu Wang, Bin Wu and Yue-Wei Guo
Mar. Drugs 2017, 15(11), 354; https://doi.org/10.3390/md15110354 - 10 Nov 2017
Cited by 83 | Viewed by 10304
Abstract
Nowadays, various drugs on the market are becoming more and more resistant to numerous diseases, thus declining their efficacy for treatment purposes in human beings. Antibiotic resistance is one among the top listed threat around the world which eventually urged the discovery of [...] Read more.
Nowadays, various drugs on the market are becoming more and more resistant to numerous diseases, thus declining their efficacy for treatment purposes in human beings. Antibiotic resistance is one among the top listed threat around the world which eventually urged the discovery of new potent drugs followed by an increase in the number of deaths caused by cancer due to chemotherapy resistance as well. Accordingly, marine cyanobacteria, being the oldest prokaryotic microorganisms belonging to a monophyletic group, have proven themselves as being able to generate pharmaceutically important natural products. They have long been known to produce distinct and structurally complex secondary metabolites including peptides, polyketides, alkaloids, lipids, and terpenes with potent biological properties and applications. As such, this review will focus on recently published novel compounds isolated from marine cyanobacteria along with their potential bioactivities such as antibacterial, antifungal, anticancer, anti-tuberculosis, immunosuppressive and anti-inflammatory capacities. Moreover, various structural classes, as well as their technological uses will also be discussed. Full article
(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))
►▼ Show Figures

Figure 1

2773 KiB  
Review
Recent Advances in the Isolation, Synthesis and Biological Activity of Marine Guanidine Alkaloids
by Jin Liu, Xu-Wen Li and Yue-Wei Guo
Mar. Drugs 2017, 15(10), 324; https://doi.org/10.3390/md15100324 - 24 Oct 2017
Cited by 27 | Viewed by 7950
Abstract
Marine organisms are prolific resources of guanidine-containing natural products with intriguing structures and promising biological activities. These molecules have therefore attracted the attention of chemists and biologists for their further studies towards potential drug leads. This review focused on the guanidine alkaloids derived [...] Read more.
Marine organisms are prolific resources of guanidine-containing natural products with intriguing structures and promising biological activities. These molecules have therefore attracted the attention of chemists and biologists for their further studies towards potential drug leads. This review focused on the guanidine alkaloids derived from marine sources and discussed the recent progress on their isolation, synthesis and biological activities, covering the literature from the year 2010 to the present. Full article
(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))
►▼ Show Figures

Figure 1

4504 KiB  
Review
Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action
by Alejandro M. S. Mayer, Abimael D. Rodríguez, Orazio Taglialatela-Scafati and Nobuhiro Fusetani
Mar. Drugs 2017, 15(9), 273; https://doi.org/10.3390/md15090273 - 29 Aug 2017
Cited by 75 | Viewed by 14664
Abstract
The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998–2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the [...] Read more.
The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998–2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012–2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories. Full article
(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-10
Back to TopTop