Novel 5′-Norcarbocyclic Pyrimidine Derivatives as Antibacterial Agents

Thumbnail Image

Files

molecules-23-03069.pdf (1.6 MB)

Links to Files

https://www.mdpi.com/1420-3049/23/12/3069

Permanent Link

https://doi.org/10.3390/molecules23123069
 http://hdl.handle.net/11603/12163

Collections

UMBC Chemistry & Biochemistry Department

Author/Creator

Author/Creator ORCID

Date

2018-11-23

Type of Work

journal articles
Text

Department

Program

Citation of Original Publication

Anastasia L. Khandazhinskaya , Liudmila A. Alexandrova , Elena S. Matyugina, Pavel N. Solyev , Olga V. Efremenkova , Karen W. Buckheit , Maggie Wilkinson , Robert W. Buckheit, Jr. , Larisa N. Chernousova , Tatiana G. Smirnova , Sofya N. Andreevskaya , Olga G. Leonova , Vladimir I. Popenko , Sergey N. Kochetkov and Katherine L. Seley-Radtke , Novel 5′-Norcarbocyclic Pyrimidine Derivatives as Antibacterial Agents, Molecules 2018, 23(12), 3069; https://doi.org/10.3390/molecules23123069

Rights

This item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
Attribution 4.0 International (CC BY 4.0)

Subjects

5′-norcarbocyclic nucleosides
mycobacterium tuberculosis
antibacterial activity
uracil derivatives

Abstract

A series of novel 5′-norcarbocyclic derivatives of 5-alkoxymethyl or 5-alkyltriazolyl-methyl uracil were synthesized and the activity of the compounds evaluated against both Gram-positive and Gram-negative bacteria. The growth of Mycobacterium smegmatis was completely inhibited by the most active compounds at a MIC99 of 67 μg/mL (mc2155) and a MIC99 of 6.7–67 μg/mL (VKPM Ac 1339). Several compounds also showed the ability to inhibit the growth of attenuated strains of Mycobacterium tuberculosis ATCC 25177 (MIC99 28–61 μg/mL) and Mycobacterium bovis ATCC 35737 (MIC99 50–60 μg/mL), as well as two virulent strains of M. tuberculosis; a laboratory strain H37Rv (MIC99 20–50 μg/mL) and a clinical strain with multiple drug resistance MS-115 (MIC99 20–50 μg/mL). Transmission electron microscopy (TEM) evaluation of M. tuberculosis H37Rv bacterial cells treated with one of the compounds demonstrated destruction of the bacterial cell wall, suggesting that the mechanism of action for these compounds may be related to their interactions with bacteria cell walls.