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Special Issue "Structure-Based Drug Design"

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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 (28 February 2010)

Special Issue Editor

Guest Editor
Prof. Dr. Claudiu T. Supuran

Neurofarba Department, University of Florence, Via Ugo Schiff 6, Polo Scientifico,50019-Sesto Fiorentino (Firenze), Italy
Website | E-Mail
Phone: +39-055-4573729/3005
Fax: +39-055-4573385
Interests: drug design; enzyme inhibitors; carbonic anhydrases; X-ray crystallography

Keywords

  • carbonic anhydrases
  • histone deacetylases
  • TACE
  • ACE
  • CGP II
  • bacterial metalloproteinases
  • APOBEC3G
  • anticancer agents
  • antivirals
  • enzyme inhibitor

Published Papers (5 papers)

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Research

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Open AccessArticle Synthesis and Biological Activity of trans-Tiliroside Derivatives as Potent Anti-Diabetic Agents
Molecules 2010, 15(12), 9174-9183; doi:10.3390/molecules15129174
Received: 29 October 2010 / Revised: 7 December 2010 / Accepted: 8 December 2010 / Published: 10 December 2010
Cited by 12 | PDF Full-text (181 KB)
Abstract
A set of novel trans-tiliroside derivatives were synthesized. The structures of the derivatives were identified by their IR, 1H-NMR, and MS spectra analysis. Their anti-diabetic activities were evaluated on the insulin resistant (IR) HepG2 cell model. As a result, compounds 7a
[...] Read more.
A set of novel trans-tiliroside derivatives were synthesized. The structures of the derivatives were identified by their IR, 1H-NMR, and MS spectra analysis. Their anti-diabetic activities were evaluated on the insulin resistant (IR) HepG2 cell model. As a result, compounds 7a, 7c, 7h, and trans-tiliroside exhibited significant glucose consumption-enhancing effects in IR-HepG2 cells compared with the positive control (metformin). This research provides useful clues for further design and discovery of anti-diabetic agents. Full article
(This article belongs to the Special Issue Structure-Based Drug Design)
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Open AccessArticle Lead Generation and Optimization Based on Protein-Ligand Complementarity
Molecules 2010, 15(6), 4382-4400; doi:10.3390/molecules15064382
Received: 24 May 2010 / Accepted: 7 June 2010 / Published: 17 June 2010
Cited by 4 | PDF Full-text (1576 KB)
Abstract
This work proposes a computational procedure for structure-based lead generation and optimization, which relies on the complementarity of the protein-ligand interactions. This procedure takes as input the known structure of a protein-ligand complex. Retaining the positions of the ligand heavy atoms in the
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This work proposes a computational procedure for structure-based lead generation and optimization, which relies on the complementarity of the protein-ligand interactions. This procedure takes as input the known structure of a protein-ligand complex. Retaining the positions of the ligand heavy atoms in the protein binding site it designs structurally similar compounds considering all possible combinations of atomic species (N, C, O, CH3, NH,etc). Compounds are ranked based on a score which incorporates energetic contributions evaluated using molecular mechanics force fields. This procedure was used to design new inhibitor molecules for three serine/threonine protein kinases (p38 MAP kinase, p42 MAP kinase (ERK2), and c-Jun N-terminal kinase 3 (JNK3)). For each enzyme, the calculations produce a set of potential inhibitors whose scores are in agreement with IC50 data and Ki values. Furthermore, the native ligands for each protein target, scored within the five top-ranking compounds predicted by our method, one of the top-ranking compounds predicted to inhibit JNK3 was synthesized and his inhibitory activity confirmed against ATP hydrolysis. Our computational procedure is therefore deemed to be a useful tool for generating chemically diverse molecules active against known target proteins. Full article
(This article belongs to the Special Issue Structure-Based Drug Design)
Open AccessArticle Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors
Molecules 2010, 15(6), 3958-3992; doi:10.3390/molecules15063958
Received: 8 March 2010 / Revised: 13 May 2010 / Accepted: 15 May 2010 / Published: 1 June 2010
Cited by 9 | PDF Full-text (3759 KB)
Abstract
Raltegravir was the first HIV-1 integrase inhibitor that gained FDA approval for use in the treatment of HIV-1 infection. Because of the emergence of IN inhibitor-resistant viral strains, there is a need to identify innovative second-generation IN inhibitors. Previously, we identified 2-thioxo-4-thiazolidinone (rhodanine)-containing
[...] Read more.
Raltegravir was the first HIV-1 integrase inhibitor that gained FDA approval for use in the treatment of HIV-1 infection. Because of the emergence of IN inhibitor-resistant viral strains, there is a need to identify innovative second-generation IN inhibitors. Previously, we identified 2-thioxo-4-thiazolidinone (rhodanine)-containing compounds as IN inhibitors. Herein, we report the design, synthesis and docking studies of a series of novel rhodanine derivatives as IN inhibitors. All these compounds were further tested against human apurinic/apyrimidinic endonuclease 1 (APE1) to determine their selectivity. Two compounds showed significant cytotoxicity in a panel of human cancer cell lines. Taken together, our results show that rhodanines are a promising class of compounds for developing drugs with antiviral and anticancer properties. Full article
(This article belongs to the Special Issue Structure-Based Drug Design)
Open AccessArticle Novel Indole-Based Analogs of Melatonin: Synthesis and in Vitro Antioxidant Activity Studies
Molecules 2010, 15(4), 2187-2202; doi:10.3390/molecules15042187
Received: 19 January 2010 / Revised: 15 March 2010 / Accepted: 23 March 2010 / Published: 29 March 2010
Cited by 32 | PDF Full-text (285 KB)
Abstract
The aim of this study was to synthesize and examine possible in vitro antioxidant effects of indole-based melatonin analogue compounds. As a part of our ongoing study nineteen indole hydrazide/hydrazone derivatives were synthesized, characterized and their in vitro antioxidant activity was investigated by
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The aim of this study was to synthesize and examine possible in vitro antioxidant effects of indole-based melatonin analogue compounds. As a part of our ongoing study nineteen indole hydrazide/hydrazone derivatives were synthesized, characterized and their in vitro antioxidant activity was investigated by three different assays: by evaluating their reducing effect against oxidation of a redox sensitive fluorescent probe, by examining their protective effect against H2O2-induced membrane lipid peroxidation and by determining their inhibitory effect on AAPH–induced hemolysis of human erythrocytes. The results indicated significant strong antioxidant activity for most of the compounds, when compared to melatonin. Full article
(This article belongs to the Special Issue Structure-Based Drug Design)

Review

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Open AccessReview 4D-QSAR: Perspectives in Drug Design
Molecules 2010, 15(5), 3281-3294; doi:10.3390/molecules15053281
Received: 1 March 2010 / Revised: 30 March 2010 / Accepted: 6 April 2010 / Published: 4 May 2010
Cited by 46 | PDF Full-text (2711 KB)
Abstract
Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate
[...] Read more.
Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate the optimization of leads into drug candidates. The quantitative structure–activity relationship (QSAR) formalisms are among the most important strategies that can be applied for the successful design new molecules. This review provides a comprehensive review on the evolution and current status of 4D-QSAR, highlighting present challenges and new opportunities in drug design. Full article
(This article belongs to the Special Issue Structure-Based Drug Design)
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