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Special Issue "Heterocycles in Medicinal Chemistry"

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

Deadline for manuscript submissions: 31 January 2019

Special Issue Editor

Guest Editor
Prof. Dr. Josef Jampilek

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, SK-832 32 Bratislava, Slovakia
Website | E-Mail
Phone: +421250117229
Interests: medicinal chemistry of anti-infective and antineoplastic; naphthalenes, quinolines; quinazolines; quinoxalines; amides; ADME; polymorphism; pharmaceutical analysis, solid-state analytical techniques

Special Issue Information

Dear Colleagues,

Heteroatoms constitute a very common fragment of a number of active pharmaceutical ingredients, as well as excipients; from the point of view of significance, it is all the same if these are isosterically/bioisosterically replaced carbons/carbon substructures in aliphatic structures or real heterocycles. Many heterocyclic scaffolds can be considered as privilege structures. Most frequently, nitrogen heterocycles or various positional combinations of nitrogen atoms, sulphur and oxygen in five- or six-membered rings can be found. According to statistics, more than 85% of all biologically-active chemical entities contain a heterocycle. This fact reflects the central role of heterocycles in modern drug design. The application of heterocycles provides a useful tool for modification of solubility, lipophilicity, polarity and hydrogen bonding capacity of biologically active agents, which results in the optimization of the ADME/Tox properties of drugs or drug candidates. The increasing presence of various heterocycles in drugs is related to advances in synthetic methodologies, such as metal-catalysed cross-coupling and hetero-coupling reactions, that allow rapid access to a wide variety of functionalized heterocycles. On the other hand, many heterocyclic lead compounds were isolated from natural resources, and their structures were subsequently simplified and modified by medicinal chemists. Thus, heterocycles have critical importance for medicinal chemists, because using them, it is possible to expand the available drug-like chemical space and drive more effective drug discovery programs. As medicinal chemistry is “a chemistry-based discipline, also involving aspects of biological, medical and pharmaceutical sciences” and “concerned with the invention, discovery, design, identification and preparation of biologically active compounds, the study of their metabolism, the interpretation of their mode of action at the molecular level and the construction of structure-activity relationships”, this Special Issue of Molecules titled “Heterocycles in Medicinal Chemistry” is devoted to the following research topics focused on heterocycles: (i) synthesis and analysis; (ii) natural compounds; (iii) carbohydrates; (iv) drug design; (v) in silico investigations; (vi) biological screening; (vii) chemical biology and biological chemistry; (vii) biomaterials; and in general, other topics related to heterocycles.

Prof. Dr. Josef Jampilek
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 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 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.

Keywords

  • drugs
  • heterocycles
  • pharmacophore
  • drug design
  • computer study
  • synthesis
  • analysis
  • natural compounds
  • carbohydrates
  • physicochemical properties
  • ADMET
  • biological screening
  • chemical biology
  • biological chemistry
  • biomaterials

Published Papers (2 papers)

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Research

Open AccessArticle Synthesis, Bacteriostatic and Anticancer Activity of Novel Phenanthridines Structurally Similar to Benzo[c]phenanthridine Alkaloids
Molecules 2018, 23(9), 2155; https://doi.org/10.3390/molecules23092155
Received: 31 July 2018 / Revised: 23 August 2018 / Accepted: 24 August 2018 / Published: 27 August 2018
PDF Full-text (1478 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, we report the synthesis, antibacterial and anticancer evaluation of 38 novel phenanthridines that were designed as analogs of the benzo[c]phenanthridine alkaloids. The prepared phenanthridines differ from the benzo[c]phenanthridines in the absence of a benzene A-ring. All
[...] Read more.
In this study, we report the synthesis, antibacterial and anticancer evaluation of 38 novel phenanthridines that were designed as analogs of the benzo[c]phenanthridine alkaloids. The prepared phenanthridines differ from the benzo[c]phenanthridines in the absence of a benzene A-ring. All novel compounds were prepared from 6-bromo-2-hydroxy-3-methoxybenzaldehyde in several synthetic steps through reduction of Schiff bases and accomplished by radical cyclization. Twelve derivatives showed high antibacterial activity against Bacillus subtilis, Micrococcus luteus and/or Mycobacterium vaccae at single digit micromolar concentrations. Some compounds also displayed cytotoxicity against the K-562 and MCF-7 cancer cell lines at as low as single digit micromolar concentrations and were more potent than chelerythrine and sanguinarine. The active compounds caused cell-cycle arrest in cancer cells, increased levels of p53 protein and caused apoptosis-specific fragmentation of PARP-1. Biological activity was connected especially with the presence of the N-methyl quaternary nitrogen and 7-benzyloxy substitution (compounds 7i, 7j, 7k, and 7l) of phenanthridine. Full article
(This article belongs to the Special Issue Heterocycles in Medicinal Chemistry)
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Open AccessArticle Synthesis of 2,6-Diamino-Substituted Purine Derivatives and Evaluation of Cell Cycle Arrest in Breast and Colorectal Cancer Cells
Molecules 2018, 23(8), 1996; https://doi.org/10.3390/molecules23081996
Received: 16 July 2018 / Revised: 6 August 2018 / Accepted: 8 August 2018 / Published: 10 August 2018
PDF Full-text (3926 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Reversine is a potent antitumor 2,6-diamino-substituted purine acting as an Aurora kinases inhibitor and interfering with cancer cell cycle progression. In this study we describe three reversine-related molecules, designed by docking calculation, that present structural modifications in the diamino units at positions 2
[...] Read more.
Reversine is a potent antitumor 2,6-diamino-substituted purine acting as an Aurora kinases inhibitor and interfering with cancer cell cycle progression. In this study we describe three reversine-related molecules, designed by docking calculation, that present structural modifications in the diamino units at positions 2 and 6. We investigated the conformations of the most stable prototropic tautomers of one of these molecules, the N6-cyclohexyl-N6-methyl-N2-phenyl-7H-purine-2,6-diamine (3), by Density Functional Theory (DFT) calculation in the gas phase, water and chloroform, the last solvent considered to give insights into the detection of broad signals in NMR analysis. In all cases the HN(9) tautomer resulted more stable than the HN(7) form, but the most stable conformations changed in different solvents. Molecules 13 were evaluated on MCF-7 breast and HCT116 colorectal cancer cell lines showing that, while being less cytotoxic than reversine, they still caused cell cycle arrest in G2/M phase and polyploidy. Unlike reversine, which produced a pronounced cell cycle arrest in G2/M phase in all the cell lines used, similar concentrations of 13 were effective only in cells where p53 was deleted or down-regulated. Therefore, our findings support a potential selective role of these structurally simplified, reversine-related molecules in p53-defective cancer cells. Full article
(This article belongs to the Special Issue Heterocycles in Medicinal Chemistry)
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