molecules-logo

Journal Browser

Journal Browser

Structure-Based Drug Design

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) | Viewed by 58562

Special Issue Editor

Neurofarba Department, Section of Farmaceutical and Neutraceutical Sciences, University of Florence, Sesto Fiorentino, 50019 Florence, Italy
Interests: drug design; metalloenzymes; carbonic anhydrases; anticancer agents; antiinfectives; sulfonamides; coumarins
Special Issues, Collections and Topics in MDPI journals

Keywords

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

Published Papers (5 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

181 KiB  
Article
Synthesis and Biological Activity of trans-Tiliroside Derivatives as Potent Anti-Diabetic Agents
by Yujin Zhu, Yanjun Zhang, Yi Liu, Hongwan Chu and Hongquan Duan
Molecules 2010, 15(12), 9174-9183; https://doi.org/10.3390/molecules15129174 - 10 Dec 2010
Cited by 25 | Viewed by 9734
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)
Show Figures

Graphical abstract

1576 KiB  
Article
Lead Generation and Optimization Based on Protein-Ligand Complementarity
by Koji Ogata, Tetsu Isomura, Shinji Kawata, Hiroshi Yamashita, Hideo Kubodera and Shoshana J. Wodak
Molecules 2010, 15(6), 4382-4400; https://doi.org/10.3390/molecules15064382 - 17 Jun 2010
Cited by 10 | Viewed by 8728
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 [...] Read more.
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)
Show Figures

Figure 1

3759 KiB  
Article
Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors
by Kavya Ramkumar, Vladimir N. Yarovenko, Alexandra S. Nikitina, Igor V. Zavarzin, Mikhail M. Krayushkin, Leonid V. Kovalenko, Adrian Esqueda, Srinivas Odde and Nouri Neamati
Molecules 2010, 15(6), 3958-3992; https://doi.org/10.3390/molecules15063958 - 01 Jun 2010
Cited by 38 | Viewed by 11448
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)
Show Figures

Figure 1

285 KiB  
Article
Novel Indole-Based Analogs of Melatonin: Synthesis and in Vitro Antioxidant Activity Studies
by Hanif Shirinzadeh, Burcu Eren, Hande Gurer-Orhan, Sibel Suzen and Seçkin Özden
Molecules 2010, 15(4), 2187-2202; https://doi.org/10.3390/molecules15042187 - 29 Mar 2010
Cited by 69 | Viewed by 10336
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 [...] Read more.
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)
Show Figures

Figure 1

Review

Jump to: Research

2711 KiB  
Review
4D-QSAR: Perspectives in Drug Design
by Carolina H. Andrade, Kerly F. M. Pasqualoto, Elizabeth I. Ferreira and Anton J. Hopfinger
Molecules 2010, 15(5), 3281-3294; https://doi.org/10.3390/molecules15053281 - 04 May 2010
Cited by 104 | Viewed by 17252
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)
Show Figures

Graphical abstract

Back to TopTop