Synthesis and Docking Study of Novel 4-Thiazolidinone Derivatives as Anti-Gram-positive and Anti-H. pylori Agents.


Journal

Mini reviews in medicinal chemistry
ISSN: 1875-5607
Titre abrégé: Mini Rev Med Chem
Pays: Netherlands
ID NLM: 101094212

Informations de publication

Date de publication:
2019
Historique:
received: 23 06 2018
revised: 10 10 2018
accepted: 10 10 2018
pubmed: 20 10 2018
medline: 5 3 2019
entrez: 19 10 2018
Statut: ppublish

Résumé

Bacterial resistance to the available antibiotics is a life threatening issue and researchers are trying to find new drugs to overcome this problem. Amongst the different structural classes, thiazolidinone-4-one, as a new effective pharmacophore against various bacteria, has been introduced. A new series of 2-(5-(5-nitrothiophene-2-yl)-1,3,4-thiadiazole-2-ylimino)-5-arylidenethiazolidin- 4-one derivatives were designed and synthesized as new antibacterial agents. Target compounds were synthesized during 5 steps and their in vitro antibacterial and anti-H. pylori activities were evaluated. The interaction of the most active derivatives with the probable targets was assessed by Auto Dock 4.2 Program. The results showed that the most potent compounds, 18, 22 and 23, displayed antibacterial activity versus S.aureus, S.epidermidis, B.cereus and B.subtilis (MIC, 1.56-12.5 µg/mL) and none of the derivatives were active on tested Gram-negative bacteria. Compound 12 in all considered doses and compounds 10, and 27 had strong anti-H. pylori activity (inhibition zone >20 mm) in 25 μg disc. Docking studies determined suitable interactions and affinity of potent compounds with bacterial MUR B and H. pylori urease enzymes. According to the results most of the derivatives are effective anti-bacterial agents and docking evaluation confirmed their possible mechanisms of actions as MURB and Urease inhibitors.

Sections du résumé

BACKGROUND BACKGROUND
Bacterial resistance to the available antibiotics is a life threatening issue and researchers are trying to find new drugs to overcome this problem. Amongst the different structural classes, thiazolidinone-4-one, as a new effective pharmacophore against various bacteria, has been introduced.
OBJECTIVE OBJECTIVE
A new series of 2-(5-(5-nitrothiophene-2-yl)-1,3,4-thiadiazole-2-ylimino)-5-arylidenethiazolidin- 4-one derivatives were designed and synthesized as new antibacterial agents.
METHOD METHODS
Target compounds were synthesized during 5 steps and their in vitro antibacterial and anti-H. pylori activities were evaluated. The interaction of the most active derivatives with the probable targets was assessed by Auto Dock 4.2 Program.
RESULTS RESULTS
The results showed that the most potent compounds, 18, 22 and 23, displayed antibacterial activity versus S.aureus, S.epidermidis, B.cereus and B.subtilis (MIC, 1.56-12.5 µg/mL) and none of the derivatives were active on tested Gram-negative bacteria. Compound 12 in all considered doses and compounds 10, and 27 had strong anti-H. pylori activity (inhibition zone >20 mm) in 25 μg disc. Docking studies determined suitable interactions and affinity of potent compounds with bacterial MUR B and H. pylori urease enzymes.
CONCLUSION CONCLUSIONS
According to the results most of the derivatives are effective anti-bacterial agents and docking evaluation confirmed their possible mechanisms of actions as MURB and Urease inhibitors.

Identifiants

pubmed: 30332951
pii: MRMC-EPUB-93778
doi: 10.2174/1389557518666181017142630
doi:

Substances chimiques

4-thiazolidinone 0
Anti-Bacterial Agents 0
Thiazolidines 0
Urease EC 3.5.1.5

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

239-249

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Armin Khomami (A)

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Mohammadamin Rahimi (M)

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Arash Tabei (A)

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Parastoo Saniee (P)

Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University G.C, Tehran, Iran.

Arash Mahboubi (A)

Food Safety Research Center, Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Alireza Foroumadi (A)

Department of Medicinal Chemistry, Faculty of Pharmacy and The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.

Nasrin Nassiri Koopaei (NN)

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Ali Almasirad (A)

Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

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Classifications MeSH