http://www.mdpi.com/journal/molecules/special_issues/drug-design/ Submission All manuscripts should be submitted to molecules@mdpi.com with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules 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 1400 CHF per accepted paper. http://www.mdpi.com/1420-3049/15/12/9174/ 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. http://www.mdpi.com/1420-3049/15/12/9174/ Fri, 10 Dec 2010 00:00:00 CET Molecules 2010-12-10 15 12 Article 9174 9183 1420-3049 Synthesis and Biological Activity of trans-Tiliroside Derivatives as Potent Anti-Diabetic Agents 2010-12-10 doi: 10.3390/molecules15129174 Yujin Zhu Yanjun Zhang Yi Liu Hongwan Chu Hongquan Duan http://www.mdpi.com/1420-3049/15/6/4382/ 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. http://www.mdpi.com/1420-3049/15/6/4382/ Thu, 17 Jun 2010 00:00:00 CEST Molecules 2010-06-17 15 6 Article 4382 4400 1420-3049 Lead Generation and Optimization Based on Protein-Ligand Complementarity 2010-06-17 doi: 10.3390/molecules15064382 Ogata Isomura Kawata Yamashita Kubodera Wodak http://www.mdpi.com/1420-3049/15/6/3958/ 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. http://www.mdpi.com/1420-3049/15/6/3958/ Tue, 01 Jun 2010 00:00:00 CEST Molecules 2010-06-01 15 6 Article 3958 3992 1420-3049 Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors 2010-06-01 doi: 10.3390/molecules15063958 Ramkumar Yarovenko Nikitina Zavarzin Krayushkin Kovalenko Esqueda Odde Neamati http://www.mdpi.com/1420-3049/15/5/3281/ 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. http://www.mdpi.com/1420-3049/15/5/3281/ Tue, 04 May 2010 00:00:00 CEST Molecules 2010-05-04 15 5 Review 3281 3294 1420-3049 4D-QSAR: Perspectives in Drug Design 2010-05-04 doi: 10.3390/molecules15053281 Andrade Pasqualoto Ferreira Hopfinger http://www.mdpi.com/1420-3049/15/4/2187/ 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. http://www.mdpi.com/1420-3049/15/4/2187/ Mon, 29 Mar 2010 00:00:00 CEST Molecules 2010-03-29 15 4 Article 2187 2202 1420-3049 Novel Indole-Based Analogs of Melatonin: Synthesis and in Vitro Antioxidant Activity Studies 2010-03-29 doi: 10.3390/molecules15042187 Shirinzadeh Eren Gurer-Orhan Suzen Özden