Small Molecule Drugs: Discovery and Development

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 2414

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Guest Editor
Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry and Tübingen Center for Academic Drug Discovery, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
Interests: development of coronavirus protease inhibitors (SARS-CoV-1 & -2 and MERS); the cathepsin L, the main protease, and the papain-like proteases are the primary targets, as well as dual SARS-CoV-2 Mpro-ki; design, synthesis, and development of small molecule modulators (agonists and antagonists) of G protein-coupled receptors
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Special Issue Information

Dear Colleagues,

The main focus of this Special Issue is the development of small molecule drugs, including their discovery, lead generation, and optimization by structure–activity relationships against a variety of diseases, including viral, inflammatory, cancerous, and neurodegenerative diseases.

Small molecules, which are organic compounds with low molecular weights (500 Daltons or less), have been the backbone of the pharma industry for almost a century. Small molecules have a number of advantages over biological and peptide drugs, including the potential to be taken orally and the ability to penetrate cell membranes to reach the desired target. Using a variety of modes of action, they can also be made to interact with biological targets. For example, the distribution of these substances can be changed to allow for systemic exposure with or without brain penetration.

We are particularly interested in submissions that deal with studies of molecules against various kinases, enzymes, GPCRs, and transcription factors with a known mode of action. Additionally, we encourage you to submit any work that makes use of cutting-edge computational methods that could lead to the discovery of novel molecules or experimentally validated results from the virtual screening of new chemical entities. We are interested in original research articles or reviews that offer fresh perspectives and thought-provoking concepts.

Dr. Thanigaimalai Pillaiyar
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 submissions that pass pre-check are 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. Biomedicines 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 2600 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.

Keywords

  • drug discovery
  • drug design and synthesis
  • in vitro testing
  • enzyme inhibitors
  • GPCR modulators
  • molecular modelling
  • small molecules
  • structure-activity relationship

Published Papers (1 paper)

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Research

19 pages, 3280 KiB  
Article
In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors
by Miglena Milusheva, Vera Gledacheva, Iliyana Stefanova, Mina Pencheva, Rositsa Mihaylova, Yulian Tumbarski, Paraskev Nedialkov, Emiliya Cherneva, Mina Todorova and Stoyanka Nikolova
Biomedicines 2023, 11(2), 605; https://doi.org/10.3390/biomedicines11020605 - 17 Feb 2023
Cited by 3 | Viewed by 1865
Abstract
Irritable bowel syndrome (IBS) is a functional gastroenterological disorder with complex pathogenesis and multifaceted therapy approaches, aimed at alleviating clinical symptoms and improving the life quality of patients. Its treatment includes dietary changes and drugs from various pharmacological groups such as antidiarrheals, anticholinergics, [...] Read more.
Irritable bowel syndrome (IBS) is a functional gastroenterological disorder with complex pathogenesis and multifaceted therapy approaches, aimed at alleviating clinical symptoms and improving the life quality of patients. Its treatment includes dietary changes and drugs from various pharmacological groups such as antidiarrheals, anticholinergics, serotonin receptor antagonists, targeting chloride ion channels, etc. The present article is focused on the synthesis and biological evaluation of some mebeverine precursors as potential antispasmodics. Methods: In silico analysis aimed at predicting the pharmacodynamic profile of the compounds was performed. Based on these predictions, ex vivo bioelectrical activity (BEA) and immunohistochemical effects of the compounds were established. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial and cytotoxic activity. Results: All the newly synthesized compounds exerted drug-like properties, whereby 3-methyl-1-phenylbutan-2-amine 3 showed a significant change in BEA due to Ca2+ channel regulation, Ca2+ influx modulation, and a subsequent change in smooth muscle cell response. The immunohistochemical studies showed a good correlation with the obtained data on the BEA, defining amine 3 as a leader structure. No cytotoxicity to human malignant leukemic cell lines (LAMA-84, K-562) was observed for all tested compounds. Conclusion: Based on the experimental results, we outlined 3-methyl-1-phenylbutan-2-amine 3 as a potential effective choice for orally active long-term therapy of IBS. Full article
(This article belongs to the Special Issue Small Molecule Drugs: Discovery and Development)
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