Exploiting the Thiobarbituric Acid Scaffold for Antibacterial Activity

Anamika Sharma; Sikabwe Noki; Sizwe J Zamisa; Heba A Hazzah; Zainab M Almarhoon; Ayman El-Faham; Beatriz G de la Torre; Fernando Albericio

doi:10.1002/cmdc.201800414

Exploiting the Thiobarbituric Acid Scaffold for Antibacterial Activity

ChemMedChem. 2018 Sep 19;13(18):1923-1930. doi: 10.1002/cmdc.201800414. Epub 2018 Aug 13.

Authors

Anamika Sharma¹, Sikabwe Noki¹, Sizwe J Zamisa², Heba A Hazzah^{1

3}, Zainab M Almarhoon⁴, Ayman El-Faham^{4

5}, Beatriz G de la Torre⁶, Fernando Albericio^{2

4

7

8}

Affiliations

¹ School of Health Sciences, University of KwaZulu-Natal, University Road, Westville, Durban, 4000, South Africa.
² School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag X54001, Westville Campus, Durban, 4000, South Africa.
³ Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria, 21641, Egypt.
⁴ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
⁵ Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Alexandria, 21321, Egypt.
⁶ KRISP, College of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001, South Africa.
⁷ Department of Organic Chemistry, University of Barcelona, Martí i Franquès 1-11, 08028, Barcelona, Spain.
⁸ CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain.

PMID: 30004647
DOI: 10.1002/cmdc.201800414

Abstract

Thiobarbituric acid (TBA) has been considered a privileged structure for developing antimicrobial agents. Diversity was obtained at positions N and at C5 through acylation, Schiff base formation, Knoevenagel condensation, and thioamide and enamine formation. The present work describes the synthesis of small libraries based on the TBA moiety and above-mentioned reactions. Preliminary antimicrobial activity screening of the prepared compounds against selected bacteria (both Gram-positive and -negative) showed the best results for the Boc-Phe-TBA derivative. These results could be useful for designing and building libraries based on other amino acids with distinct protecting groups.

Keywords: antibiotics; barbituric acid; nanoformulations; thiobarbituric acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Bacillus subtilis / drug effects*
Dose-Response Relationship, Drug
Escherichia coli / drug effects*
Microbial Sensitivity Tests
Molecular Structure
Pseudomonas aeruginosa / drug effects*
Staphylococcus aureus / drug effects*
Structure-Activity Relationship
Thiobarbiturates / chemical synthesis
Thiobarbiturates / chemistry
Thiobarbiturates / pharmacology*

Substances

Anti-Bacterial Agents
Thiobarbiturates
thiobarbituric acid