The contribution of oxazolidinone frame to the biological activity of pharmaceutical drugs and natural products.
| Title: | The contribution of oxazolidinone frame to the biological activity of pharmaceutical drugs and natural products. |
|---|---|
| Authors: | Zappia G; Ist. di Chimica Farmaceutica, Universită degli Studi di Urbino 'Carlo Bo', P.za del Rinascimento 6, 61029 Urbino, Italy. g.zappia@uniurb.it; Menendez P; Monache GD; Misiti D; Nevola L; Botta B |
| Source: | Mini reviews in medicinal chemistry [Mini Rev Med Chem] 2007 Apr; Vol. 7 (4), pp. 389-409. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't; Review |
| Language: | English |
| Journal Info: | Publisher: Bentham Science Publishers Country of Publication: Netherlands NLM ID: 101094212 Publication Model: Print Cited Medium: Print ISSN: 1389-5575 (Print) Linking ISSN: 13895575 NLM ISO Abbreviation: Mini Rev Med Chem Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Hilversum, The Netherlands; Boca Raton, FL : Bentham Science Publishers, c2001- |
| MeSH Terms: | Biological Products/*pharmacology ; Oxazolidinones/*pharmacology ; Pharmaceutical Preparations/*chemistry; Biological Products/chemistry ; Oxazolidinones/chemistry ; Humans ; Structure-Activity Relationship |
| Abstract: | The development of resistance by the antibiotics in the Gram-positive pathogenic bacteria over the last twenty years and continuing today has created a need for new antibiotic classes, which may be unaffected by existing bacterial resistance. The oxazolidin-2-ones represent not only a new class with a novel mechanism of action, but also satisfy the requirement for overcoming the resistance mechanisms. Both linezolid and eperozolid, the first chemical candidates, arose from the piperazine subclass, with the first one being chosen further development because of its enhanced pharmacokinetic properties. The main attractive traits of the oxazolidinone series has encouraged further work in the area, and the patent literature reveals that extensive chemical investigation is currently being made. The unexpected early resistance development emphasizes the need for further exploration of features of the oxazolidinone to eliminate these deficiencies. Recently, several changes, involving the C5 side chain as well the N-phenyl heterocyclic ring, give promise for such improvement. Oxazolidinone antibacterial agents comprise also ketolides, derivatives of macrolides, such as erythromycin A, with a newly formed carbamate cycle, with a largely unexplored potential. The oxazolidinone nucleus does not appear only in the structures of antimicrobial drugs, but a number of biological activities are connected with frameworks including the oxazolidinone ring. A partial list of these activities comprises enzyme inhibitors, agonists and antagonists, with a particular citation for a new generation of selective monoamino oxidase inhibitors (befloxatone). The oxazolidinone moiety was found in the structure of few biologically active natural products, such as (-)-cytoxazone and streptazolin. Moreover, in some cases the oxazolidinone ring has been chosen for the preparation of isosteric aza analogues of natural compounds (podophyllotoxin, pilocarpine) that can be more easily synthesised and more hardly inactivated. Finally, the participation of oxazolidinone chiral auxiliaries to several syntheses of natural products must be acknowledged. |
| Number of References: | 86 |
| Substance Nomenclature: | 0 (Biological Products); 0 (Oxazolidinones); 0 (Pharmaceutical Preparations) |
| Entry Date(s): | Date Created: 20070414 Date Completed: 20070510 Latest Revision: 20190917 |
| Update Code: | 20260130 |
| DOI: | 10.2174/138955707780363783 |
| PMID: | 17430225 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't; Review