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Special Issue "Structure-Based Design of Biologically Active Compounds"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 31 December 2019

Special Issue Editor

Guest Editor
Prof. Dr. Sandra Gemma

Department of Biotechnology, chemistry and pharmacy, University of Siena via Aldo Moro 2, 53100 Siena, Italy
Website | E-Mail
Interests: medicinal chemistry; small molecules, drug discovery; structure-activity relationships; anti-infective agents; parasitic diseases; chemotherapeutics; synthesis of biologically active compounds

Special Issue Information

Dear Colleagues,

This Special Issue is entitled “Structure-based design of biologically active compounds”. The identification of new drugs is a challenging process characterized by a high attrition rate. In this context, structure-based design has long been used as an important and irreplaceable strategy in all the different steps of the drug discovery process such as hit identification, hit-to-lead progression, optimization of selectivity, off-target affinity, and drug-like properties. In recent years, significant advances in molecular biology, production of high quality proteins, and X-ray crystallography techniques (e.g. cryo bio-crystallography) has allowed a tremendous increase in our detailed structural knowledge of biologically-relevant target proteins. The rapid pace of development of new tools to better understand the structure and function of proteins, disease complexity, and pathophysiological correlations continues to fuel new potential targets for the development of innovative drugs. Structure-based design has the potential of addressing the challenges of modern medicinal chemistry in newly developing fields. Recent advances in network and systems biology has allowed the study of drug targets in their physiological context, fostering drug discovery approaches able to tackle the complexity of multifactorial diseases through the design of multitargeting ligands. The design of small molecules able to target protein–protein interactions is another challenging goal for which the contribution of structure-based design will be essential. As a last example, high-resolution structural knowledge of GPCR receptors has opened exciting new opportunities for the design of bitopic, divalent or biased ligands. This Special Issue will cover all the different aspects of structure-based design, leading to biologically active compounds, from hit/lead generation based on the structural knowledge of the target (X-ray or homology modeling), to molecular docking, synthetic chemistry, and structure–activity relationships for ligand optimization.

Prof. Dr. Sandra Gemma
Guest Editor

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 papers will be 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. Molecules is an international peer-reviewed open access semimonthly 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 1800 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.


  • Structure-based design
  • Hit-to-lead transition
  • Molecular modeling
  • Small molecules
  • Enzyme inhibitors
  • Multitargeting ligands
  • Protein–protein interaction inhibitors
  • Structure–activity relationships

Published Papers (1 paper)

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Open AccessArticle
Dihydropyrazole Derivatives Containing Benzo Oxygen Heterocycle and Sulfonamide Moieties Selectively and Potently Inhibit COX-2: Design, Synthesis, and Anti-Colon Cancer Activity Evaluation
Molecules 2019, 24(9), 1685; https://doi.org/10.3390/molecules24091685
Received: 11 March 2019 / Revised: 17 April 2019 / Accepted: 18 April 2019 / Published: 30 April 2019
PDF Full-text (3788 KB) | HTML Full-text | XML Full-text | Supplementary Files
Cyclooxygenase-2 (COX-2) as a rate-limiting metabolism enzyme of arachidonic acid has been found to be implicated in tumor occurrence, angiogenesis, metastasis as well as apoptosis inhibition, regarded as an attractive therapeutic target for cancer therapy. In our research, a series of dihydropyrazole derivatives [...] Read more.
Cyclooxygenase-2 (COX-2) as a rate-limiting metabolism enzyme of arachidonic acid has been found to be implicated in tumor occurrence, angiogenesis, metastasis as well as apoptosis inhibition, regarded as an attractive therapeutic target for cancer therapy. In our research, a series of dihydropyrazole derivatives containing benzo oxygen heterocycle and sulfonamide moieties were designed as highly potent and selective COX-2 inhibitors by computer-aided drug analysis of known COX-2 inhibitors. A total of 26 compounds were synthesized and evaluated COX-2 inhibition and pharmacological efficiency both in vitro and in vivo with multi-angle of view. Among them, compound 4b exhibited most excellent anti-proliferation activities against SW620 cells with IC50 of 0.86 ± 0.02 µM than Celecoxib (IC50 = 1.29 ± 0.04 µM). The results favored our rational design intention and provides compound 4b as an effective COX-2 inhibitor available for the development of colon tumor therapeutics. Full article
(This article belongs to the Special Issue Structure-Based Design of Biologically Active Compounds)

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