Pharmaceuticals

2715 KiB

Open AccessArticle

Activity of Gallium Meso- and Protoporphyrin IX against Biofilms of Multidrug-Resistant Acinetobacter baumannii Isolates

by David Chang, Rebecca A. Garcia, Kevin S. Akers, Katrin Mende, Clinton K. Murray, Joseph C. Wenke and Carlos J. Sanchez

Pharmaceuticals 2016, 9(1), 16; https://doi.org/10.3390/ph9010016 - 17 Mar 2016

Cited by 30 | Viewed by 5980

Abstract

Acinetobacter baumannii is a challenging pathogen due to antimicrobial resistance and biofilm development. The role of iron in bacterial physiology has prompted the evaluation of iron-modulation as an antimicrobial strategy. The non-reducible iron analog gallium(III) nitrate, Ga(NO₃)₃, has been [...] Read more.

Acinetobacter baumannii is a challenging pathogen due to antimicrobial resistance and biofilm development. The role of iron in bacterial physiology has prompted the evaluation of iron-modulation as an antimicrobial strategy. The non-reducible iron analog gallium(III) nitrate, Ga(NO₃)₃, has been shown to inhibit A. baumannii planktonic growth; however, utilization of heme-iron by clinical isolates has been associated with development of tolerance. These observations prompted the evaluation of iron-heme sources on planktonic and biofilm growth, as well as antimicrobial activities of gallium meso- and protoporphyrin IX (Ga-MPIX and Ga-PPIX), metal heme derivatives against planktonic and biofilm bacteria of multidrug-resistant (MDR) clinical isolates of A. baumannii in vitro. Ga(NO₃)₃ was moderately effective at reducing planktonic bacteria (64 to 128 µM) with little activity against biofilms (≥512 µM). In contrast, Ga-MPIX and Ga-PPIX were highly active against planktonic bacteria (0.25 to 8 µM). Cytotoxic effects in human fibroblasts were observed following exposure to concentrations exceeding 128 µM of Ga-MPIX and Ga-PPIX. We observed that the gallium metal heme conjugates were more active against planktonic and biofilm bacteria, possibly due to utilization of heme-iron as demonstrated by the enhanced effects on bacterial growth and biofilm formation. Full article

(This article belongs to the Special Issue Microbial Biofilms)

► Show Figures

Figure 1

13853 KiB

Open AccessMeeting Report

11^th National Meeting of Organic Chemistry and 4^th Meeting of Therapeutic Chemistry

by Maria Emília Sousa, Maria João Araújo, Maria Luísa Do Vale, Paula B. Andrade, Paula Branco, Paula Gomes, Rui Moreira, Teresa M.V.D. Pinho e Melo and Victor Freitas

Pharmaceuticals 2016, 9(1), 15; https://doi.org/10.3390/ph9010015 - 17 Mar 2016

Cited by 1 | Viewed by 9906

Abstract

For the first time under the auspices of Sociedade Portuguesa de Química, the competences of two important fields of Chemistry are brought together into a single event, the 11st National Organic Chemistry Meeting and the the 4th National Medicinal Chemistry Meeting, to highlight [...] Read more.

For the first time under the auspices of Sociedade Portuguesa de Química, the competences of two important fields of Chemistry are brought together into a single event, the 11st National Organic Chemistry Meeting and the the 4th National Medicinal Chemistry Meeting, to highlight complementarities and to promote new synergies. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report. Full article

(This article belongs to the Special Issue Selected papers from the 11th National Meeting of Organic Chemistry and 4th Meeting of Therapeutic Chemistry in Portugal)

5054 KiB

Open AccessMeeting Report

First International Electronic Conference on Medicinal Chemistry (ECMC-1)

by Annie Mayence and Jean Jacques Vanden Eynde

Pharmaceuticals 2016, 9(1), 14; https://doi.org/10.3390/ph9010014 - 11 Mar 2016

Cited by 2 | Viewed by 7595

Abstract

The first International Electronic Conference on Medicinal Chemistry, organized and sponsored by MDPI AG, publisher, and the Journal Pharmaceuticals, took place in November 2015 on the SciForum website. More than 200 authors from 18 countries participated in the event and was attended by [...] Read more.

The first International Electronic Conference on Medicinal Chemistry, organized and sponsored by MDPI AG, publisher, and the Journal Pharmaceuticals, took place in November 2015 on the SciForum website. More than 200 authors from 18 countries participated in the event and was attended by 25,000 visitors who had the opportunity to browse among 55 presentations, keynotes, and videos. A short description of some works presented during that scientific meeting is disclosed in this report. Full article

(This article belongs to the Special Issue Selected Papers from the 1st International Electronic Conference on Medicinal Chemistry)

► Show Figures

Figure 1

3388 KiB

Open AccessReview

Potential Use of Antimicrobial Peptides as Vaginal Spermicides/Microbicides

by Nongnuj Tanphaichitr, Nopparat Srakaew, Rhea Alonzi, Wongsakorn Kiattiburut, Kessiri Kongmanas, Ruina Zhi, Weihua Li, Mark Baker, Guanshun Wang and Duane Hickling

Pharmaceuticals 2016, 9(1), 13; https://doi.org/10.3390/ph9010013 - 11 Mar 2016

Cited by 43 | Viewed by 13676

Abstract

The concurrent increases in global population and sexually transmitted infection (STI) demand a search for agents with dual spermicidal and microbicidal properties for topical vaginal application. Previous attempts to develop the surfactant spermicide, nonoxynol-9 (N-9), into a vaginal microbicide were unsuccessful largely due [...] Read more.

The concurrent increases in global population and sexually transmitted infection (STI) demand a search for agents with dual spermicidal and microbicidal properties for topical vaginal application. Previous attempts to develop the surfactant spermicide, nonoxynol-9 (N-9), into a vaginal microbicide were unsuccessful largely due to its inefficiency to kill microbes. Furthermore, N-9 causes damage to the vaginal epithelium, thus accelerating microbes to enter the women’s body. For this reason, antimicrobial peptides (AMPs), naturally secreted by all forms of life as part of innate immunity, deserve evaluation for their potential spermicidal effects. To date, twelve spermicidal AMPs have been described including LL-37, magainin 2 and nisin A. Human cathelicidin LL-37 is the most promising spermicidal AMP to be further developed for vaginal use for the following reasons. First, it is a human AMP naturally produced in the vagina after intercourse. Second, LL-37 exerts microbicidal effects to numerous microbes including those that cause STI. Third, its cytotoxicity is selective to sperm and not to the female reproductive tract. Furthermore, the spermicidal effects of LL-37 have been demonstrated in vivo in mice. Therefore, the availability of LL-37 as a vaginal spermicide/microbicide will empower women for self-protection against unwanted pregnancies and STI. Full article

(This article belongs to the Special Issue Antimicrobial Peptides: Expanded Activity Spectrum and Applications)

► Show Figures

Graphical abstract

973 KiB

Open AccessShort Note

Minimally-Myelosuppressive Asparaginase-Containing Induction Regimen for Treatment of a Jehovah’s Witness with mutant IDH1/NPM1/NRAS Acute Myeloid Leukemia

by Ashkan Emadi, Najeebah A. Bade, Brandi Stevenson and Zeba Singh

Pharmaceuticals 2016, 9(1), 12; https://doi.org/10.3390/ph9010012 - 10 Mar 2016

Cited by 7 | Viewed by 6503

Abstract

Treatment of patients with acute myeloid leukemia (AML) who do not wish to accept blood product transfusion, including Jehovah’s Witnesses, is extremely challenging. The use of conventional chemotherapy for induction of complete remission (CR) results in profound anemia and thrombocytopenia requiring frequent transfusions [...] Read more.

Treatment of patients with acute myeloid leukemia (AML) who do not wish to accept blood product transfusion, including Jehovah’s Witnesses, is extremely challenging. The use of conventional chemotherapy for induction of complete remission (CR) results in profound anemia and thrombocytopenia requiring frequent transfusions of blood products, without which such treatment will be life-threatening. Finding a well tolerable, minimally myelosuppressive induction regimen for such patients with AML is a clear example of area of unmet medical need. Here, we report a successful treatment of a 52-year-old Jehovah’s Witness with newly diagnosed AML with peg-asparaginase, vincristine and methylprednisolone. The AML was characterized with normal karyotype, and mutations in isocitrate dehydrogenase 1 (IDH1-Arg132Ser), nucleophosmin 1 (NPM1-Trp289Cysfs*12) and neuroblastoma RAS viral oncogene homolog (NRAS-G1y12Va1). After one 28-day cycle of treatment, the patient achieved complete remission with incomplete count recovery (CRi) and after the second cycle, he achieved CR with full blood count recovery. The patient has never received any blood products. Notwithstanding that myeloperoxidase-induced oxidative degradation of vincristine results in its lack of activity as monotherapy in AML, its combination with corticosteroid and asparaginase has resulted in a robust remission in this patient. Diminished steroid clearance by asparaginase activity as well as reduction in serum glutamine level induced by glutaminase enzymatic activity of asparaginase may have contributed to effective killing of the myeloblasts that carry IDH1/NPM1/NRAS mutations. In conclusion, asparaginase-containing regimens, which are approved for treatment of acute lymphoblastic leukemia (ALL) but not AML, can be used to treat patients with AML who do not accept blood transfusion. Full article

(This article belongs to the Special Issue Chemotherapeutic Agents)

► Show Figures

Figure 1

1730 KiB

Open AccessReview

Targeting Cell Survival Proteins for Cancer Cell Death

by Manoj K. Pandey, Sahdeo Prasad, Amit Kumar Tyagi, Lokesh Deb, Jiamin Huang, Deepkamal N. Karelia, Shantu G. Amin and Bharat B. Aggarwal

Pharmaceuticals 2016, 9(1), 11; https://doi.org/10.3390/ph9010011 - 25 Feb 2016

Cited by 37 | Viewed by 8245

Abstract

Escaping from cell death is one of the adaptations that enable cancer cells to stave off anticancer therapies. The key players in avoiding apoptosis are collectively known as survival proteins. Survival proteins comprise the Bcl-2, inhibitor of apoptosis (IAP), and heat shock protein [...] Read more.

Escaping from cell death is one of the adaptations that enable cancer cells to stave off anticancer therapies. The key players in avoiding apoptosis are collectively known as survival proteins. Survival proteins comprise the Bcl-2, inhibitor of apoptosis (IAP), and heat shock protein (HSP) families. The aberrant expression of these proteins is associated with a range of biological activities that promote cancer cell survival, proliferation, and resistance to therapy. Several therapeutic strategies that target survival proteins are based on mimicking BH3 domains or the IAP-binding motif or competing with ATP for the Hsp90 ATP-binding pocket. Alternative strategies, including use of nutraceuticals, transcriptional repression, and antisense oligonucleotides, provide options to target survival proteins. This review focuses on the role of survival proteins in chemoresistance and current therapeutic strategies in preclinical or clinical trials that target survival protein signaling pathways. Recent approaches to target survival proteins-including nutraceuticals, small-molecule inhibitors, peptides, and Bcl-2-specific mimetic are explored. Therapeutic inventions targeting survival proteins are promising strategies to inhibit cancer cell survival and chemoresistance. However, complete eradication of resistance is a distant dream. For a successful clinical outcome, pretreatment with novel survival protein inhibitors alone or in combination with conventional therapies holds great promise. Full article

(This article belongs to the Special Issue Chemotherapeutic Agents)

► Show Figures

Graphical abstract

420 KiB

Open AccessCommentary

Odontonutraceuticals: Pleiotropic Phytotherapeutic Agents for Oral Health

by Elena Maria Varoni and Marcello Iriti

Pharmaceuticals 2016, 9(1), 10; https://doi.org/10.3390/ph9010010 - 25 Feb 2016

Cited by 5 | Viewed by 4104

Abstract

This brief commentary aims to focus on the urgency of further clinical research on phytotherapy in dentistry, and, noteworthy, to propose, for the first time, to the best of our knowledge, the term “odontonutraceuticals” to identify those phytochemicals relevant for the prevention and [...] Read more.

This brief commentary aims to focus on the urgency of further clinical research on phytotherapy in dentistry, and, noteworthy, to propose, for the first time, to the best of our knowledge, the term “odontonutraceuticals” to identify those phytochemicals relevant for the prevention and the treatment of oral diseases. A valuable impact is expected on nutritional, dental and biomedical sciences, suggesting the use of the suffix "odonto-" to define a specific field of nutraceutical research. Full article

► Show Figures

Figure 1

578 KiB

Open AccessReview

Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease

by Flavie Darcet, Alain M. Gardier, Raphael Gaillard, Denis J. David and Jean-Philippe Guilloux

Pharmaceuticals 2016, 9(1), 9; https://doi.org/10.3390/ph9010009 - 17 Feb 2016

Cited by 64 | Viewed by 12265

Abstract

Major Depressive Disorder (MDD) is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in [...] Read more.

Major Depressive Disorder (MDD) is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in attention, working memory, learning and memory or executive functions are often reported. However, available data about the heterogeneity of MDD patients and magnitude of cognitive symptoms through the different phases of MDD remain difficult to summarize. Thus, the first part of this review briefly overviewed clinical studies, focusing on the cognitive dysfunctions depending on the MDD type. As animal models are essential translational tools for underpinning the mechanisms of cognitive deficits in MDD, the second part of this review synthetized preclinical studies observing cognitive deficits in different rodent models of anxiety/depression. For each cognitive domain, we determined whether deficits could be shared across models. Particularly, we established whether specific stress-related procedures or unspecific criteria (such as species, sex or age) could segregate common cognitive alteration across models. Finally, the role of adult hippocampal neurogenesis in rodents in cognitive dysfunctions during MDD state was also discussed. Full article

► Show Figures

Graphical abstract

665 KiB

Open AccessArticle

Propofol and AZD3043 Inhibit Adult Muscle and Neuronal Nicotinic Acetylcholine Receptors Expressed in Xenopus Oocytes

by Malin Jonsson Fagerlund, Johannes Krupp and Michael A. Dabrowski

Pharmaceuticals 2016, 9(1), 8; https://doi.org/10.3390/ph9010008 - 6 Feb 2016

Cited by 14 | Viewed by 5740

Abstract

Propofol is a widely used general anaesthetic with muscle relaxant properties. Similarly as propofol, the new general anaesthetic AZD3043 targets the GABA_A receptor for its anaesthetic effects, but the interaction with nicotinic acetylcholine receptors (nAChRs) has not been investigated. Notably, there is [...] Read more.

Propofol is a widely used general anaesthetic with muscle relaxant properties. Similarly as propofol, the new general anaesthetic AZD3043 targets the GABA_A receptor for its anaesthetic effects, but the interaction with nicotinic acetylcholine receptors (nAChRs) has not been investigated. Notably, there is a gap of knowledge about the interaction between propofol and the nAChRs found in the adult neuromuscular junction. The objective was to evaluate whether propofol or AZD3043 interact with the α1β1δε, α3β2, or α7 nAChR subtypes that can be found in the neuromuscular junction and if there are any differences in affinity for those subtypes between propofol and AZD3043. Human nAChR subtypes α1β1δε, α3β2, and α7 were expressed into Xenopus oocytes and studied with an automated voltage-clamp. Propofol and AZD3043 inhibited ACh-induced currents in all of the nAChRs studied with inhibitory concentrations higher than those needed for general anaesthesia. AZD3043 was a more potent inhibitor at the adult muscle nAChR subtype compared to propofol. Propofol and AZD3043 inhibit nAChR subtypes that can be found in the adult NMJ in concentrations higher than needed for general anaesthesia. This finding needs to be evaluated in an in vitro nerve-muscle preparation and suggests one possible explanation for the muscle relaxant effect of propofol seen during higher doses. Full article

► Show Figures

Figure 1

1751 KiB

Open AccessArticle

Biomolecules and Natural Medicine Preparations: Analysis of New Sources of Bioactive Compounds from Ribes and Rubus spp. Buds

by Dario Donno, Maria Gabriella Mellano, Alessandro Kim Cerutti and Gabriele Loris Beccaro

Pharmaceuticals 2016, 9(1), 7; https://doi.org/10.3390/ph9010007 - 5 Feb 2016

Cited by 21 | Viewed by 8701

Abstract

It is well known that plants are important sources for the preparation of natural remedies as they contain many biologically active compounds. In particular, polyphenols, terpenic compounds, organic acids, and vitamins are the most widely occurring groups of phytochemicals. Some endemic species may [...] Read more.

It is well known that plants are important sources for the preparation of natural remedies as they contain many biologically active compounds. In particular, polyphenols, terpenic compounds, organic acids, and vitamins are the most widely occurring groups of phytochemicals. Some endemic species may be used for the production of herbal preparations containing phytochemicals with significant bioactivity, as antioxidant activity and anti-inflammatory capacities, and health benefits. Blackberry sprouts and blackcurrant buds are known to contain appreciable levels of bioactive compounds, including flavonols, phenolic acids, monoterpenes, vitamin C, and catechins, with several clinical effects. The aim of this research was to perform an analytical study of blackcurrant and blackberry bud-preparations, in order to identify and quantify the main biomarkers, obtaining a specific phytochemical fingerprint to evaluate the single botanical class contribution to total phytocomplex and relative bioactivity, using a High Performance Liquid Chromatograph−Diode Array Detector; the same analyses were performed both on the University laboratory and commercial preparations. Different chromatographic methods were used to determine concentrations of biomolecules in the preparations, allowing for quantification of statistically significant differences in their bioactive compound content both in the case of Ribes nigrum and Rubus cultivated varieties at different harvest stages. In blackcurrant bud-extracts the most important class was organic acids (50.98%) followed by monoterpenes (14.05%), while in blackberry preparations the main bioactive classes were catechins (50.06%) and organic acids (27.34%). Chemical, pharmaceutical and agronomic-environmental knowledge could be important for obtaining label certifications for the valorization of specific genotypes, with high clinical and pharmaceutical value: this study allowed to develop an effective tool for the natural preparation quality control and bioactivity evaluation through the chemical fingerprinting of bud preparations. Full article

(This article belongs to the Special Issue Selected Papers from the 1st International Electronic Conference on Medicinal Chemistry)

► Show Figures

Graphical abstract

163 KiB

Open AccessEditorial

2015: A Transition Year for Pharmaceuticals?

by Jean Jacques Vanden Eynde

Pharmaceuticals 2016, 9(1), 6; https://doi.org/10.3390/ph9010006 - 27 Jan 2016

Cited by 2 | Viewed by 3752

Abstract

In this period, I could not start this editorial without wishing all of you a Happy New Year. This is also the opportunity for me to warmly thank, for their confidence, our authors, readers, reviewers, members of the editorial board, sponsors, as well [...] Read more.

In this period, I could not start this editorial without wishing all of you a Happy New Year. This is also the opportunity for me to warmly thank, for their confidence, our authors, readers, reviewers, members of the editorial board, sponsors, as well as members of MDPI AG in Basel, Beijing, and Wuhan. [...] Full article

653 KiB

Open AccessEditorial

Acknowledgement to Reviewers of Pharmaceuticals in 2015

by Pharmaceuticals Editorial Office

Pharmaceuticals 2016, 9(1), 5; https://doi.org/10.3390/ph9010005 - 21 Jan 2016

Viewed by 3190

Abstract

The editors of Pharmaceuticals would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2015. [...] Full article

2602 KiB

Open AccessArticle

Hydroxylated Dimeric Naphthoquinones Increase the Generation of Reactive Oxygen Species, Induce Apoptosis of Acute Myeloid Leukemia Cells and Are Not Substrates of the Multidrug Resistance Proteins ABCB1 and ABCG2

by Rena G. Lapidus, Brandon A. Carter-Cooper, Mariola Sadowska, Eun Yong Choi, Omasiri Wonodi, Nidal Muvarak, Karthika Natarajan, Lakshmi S. Pidugu, Anil Jaiswal, Eric A. Toth, Feyruz V. Rassool, Arash Etemadi, Edward A. Sausville, Maria R. Baer and Ashkan Emadi

Pharmaceuticals 2016, 9(1), 4; https://doi.org/10.3390/ph9010004 - 19 Jan 2016

Cited by 8 | Viewed by 6759

Abstract

Selective targeting of the oxidative state, which is a tightly balanced fundamental cellular property, is an attractive strategy for developing novel anti-leukemic chemotherapeutics with potential applications in the treatment of acute myeloid leukemia (AML), a molecularly heterogeneous disease. Dimeric naphthoquinones (BiQs) with the [...] Read more.

Selective targeting of the oxidative state, which is a tightly balanced fundamental cellular property, is an attractive strategy for developing novel anti-leukemic chemotherapeutics with potential applications in the treatment of acute myeloid leukemia (AML), a molecularly heterogeneous disease. Dimeric naphthoquinones (BiQs) with the ability to undergo redox cycling and to generate reactive oxygen species (ROS) in cancer cells are a novel class of compounds with unique characteristics that make them excellent candidates to be tested against AML cells. We evaluated the effect of two BiQ analogues and one monomeric naphthoquinone in AML cell lines and primary cells from patients. All compounds possess one halogen and one hydroxyl group on the quinone cores. Dimeric, but not monomeric, naphthoquinones demonstrated significant anti-AML activity in the cell lines and primary cells from patients with favorable therapeutic index compared to normal hematopoietic cells. BiQ-1 effectively inhibited clonogenicity and induced apoptosis as measured by Western blotting and Annexin V staining and mitochondrial membrane depolarization by flow cytometry. BiQ-1 significantly enhances intracellular ROS levels in AML cells and upregulates expression of key anti-oxidant protein, Nrf2. Notably, systemic exposure to BiQ-1 was well tolerated in mice. In conclusion, we propose that BiQ-induced therapeutic augmentation of ROS in AML cells with dysregulation of antioxidants kill leukemic cells while normal cells remain relatively intact. Further studies are warranted to better understand this class of potential chemotherapeutics. Full article

(This article belongs to the Special Issue Chemotherapeutic Agents)

► Show Figures

Figure 1

389 KiB

Open AccessReview

The Role of Immunotherapy in Multiple Myeloma

by Mehmet Kocoglu and Ashraf Badros

Pharmaceuticals 2016, 9(1), 3; https://doi.org/10.3390/ph9010003 - 14 Jan 2016

Cited by 20 | Viewed by 7997

Abstract

Multiple myeloma is the second most common hematologic malignancy. The treatment of this disease has changed considerably over the last two decades with the introduction to the clinical practice of novel agents such as proteasome inhibitors and immunomodulatory drugs. Basic research efforts towards [...] Read more.

Multiple myeloma is the second most common hematologic malignancy. The treatment of this disease has changed considerably over the last two decades with the introduction to the clinical practice of novel agents such as proteasome inhibitors and immunomodulatory drugs. Basic research efforts towards better understanding of normal and missing immune surveillence in myeloma have led to development of new strategies and therapies that require the engagement of the immune system. Many of these treatments are under clinical development and have already started providing encouraging results. We, for the second time in the last two decades, are about to witness another shift of the paradigm in the management of this ailment. This review will summarize the major approaches in myeloma immunotherapies. Full article

(This article belongs to the Special Issue Chemotherapeutic Agents)

► Show Figures

Figure 1

5657 KiB

Open AccessFeature PaperCommunication

3,1-Benzothiazines, 1,4-Benzodioxines and 1,4-Benzoxazines as Inhibitors of Matriptase-2: Outcome of a Focused Screening Approach

by Polya G. Roydeva, Anna-Madeleine Beckmann, Marit Stirnberg, Jožko Cesar, Danijel Kikelj, Janez Ilaš and Michael Gütschow

Pharmaceuticals 2016, 9(1), 2; https://doi.org/10.3390/ph9010002 - 13 Jan 2016

Cited by 7 | Viewed by 5900

Abstract

The liver enzyme matriptase-2 is a multi-domain, transmembrane serine protease with an extracellular, C-terminal catalytic domain. Synthetic low-molecular weight inhibitors of matriptase-2 have potential as therapeutics to treat iron overload syndromes, in particular in patients with β-thalassemia. A sub-library of 64 compounds was [...] Read more.

The liver enzyme matriptase-2 is a multi-domain, transmembrane serine protease with an extracellular, C-terminal catalytic domain. Synthetic low-molecular weight inhibitors of matriptase-2 have potential as therapeutics to treat iron overload syndromes, in particular in patients with β-thalassemia. A sub-library of 64 compounds was screened for matriptase-2 inhibition and several active compounds were identified. (S)-Ethyl 2-(benzyl(3-((4-carbamidoylphenoxy)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-2-oxoacetate ((S)-12) showed an IC₅₀ value of less than 10 µM. Structure-activity relationships were discussed and proposals to design new matriptase-2 inhibitors were made. Full article

(This article belongs to the Special Issue Choices of the Journal)

► Show Figures

Graphical abstract

7560 KiB

Open AccessMeeting Report

1st Joint European Conference on Therapeutic Targets and Medicinal Chemistry (TTMC 2015)

by Marc Le Borgne, Samer Haidar, Olivier Duval, Bernhard Wünsch and Joachim Jose

Pharmaceuticals 2016, 9(1), 1; https://doi.org/10.3390/ph9010001 - 26 Dec 2015

Viewed by 9589

Abstract

The European Conference on Therapeutic Targets and Medicinal Chemistry is a new two-day meeting on drug discovery that is focused on therapeutic targets and the use of tools to explore all fields of drug discovery and drug design such as molecular modelling, bioorganic [...] Read more.

The European Conference on Therapeutic Targets and Medicinal Chemistry is a new two-day meeting on drug discovery that is focused on therapeutic targets and the use of tools to explore all fields of drug discovery and drug design such as molecular modelling, bioorganic chemistry, NMR studies, fragment screening, in vitro assays, in vivo assays, structure activity relationships, autodisplay. Abstracts of keynote lectures, plenary lectures, junior lectures, flash presentations, and posters presented during the meeting are collected in this report. Full article

(This article belongs to the Special Issue Choices of the Journal)

Journal Menu

Journal Browser

Pharmaceuticals, Volume 9, Issue 1 (March 2016) – 16 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI