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Monatshefte für Chemie - Chemical Monthly

, Volume 150, Issue 11, pp 1999–2010 | Cite as

Design and synthesis of sulfur cross-linked 1,3,4-oxadiazole-nitro(furan/thiophene)-propenones as dual inhibitors of inflammation and tuberculosis: molecular docking and Hirshfeld surface analysis

  • Vishwanath Turukarabettu
  • Balakrishna KallurayaEmail author
  • Monika Sharma
Original Paper
  • 38 Downloads

Abstract

A series of 3-[5-nitro(furan/thiophene)-2-yl]-1-aryl-3-(5-aryl-1,3,4-oxadiazol-2-ylthio)prop-2-en-1-one derivatives was synthesized and studied with the aim of developing dual inhibitors of multidrug-resistant tuberculosis and inflammation. The in vivo anti-inflammatory activity results showed excellent inhibition of rat paw edema. The methoxybenzene/nitrofuryl derivative of title compounds showed 83% inhibition of inflammation during 2–6 h after carrageenan injection. All compounds showed anti-tuberculosis activity at MIC of 50 µg/cm3. The molecular docking studies revealed that the oxadiazole and nitrofuran groups played a significant role in the inhibiting site of the enzymes COX1, COX2, 5-LOs, and InhA by forming hydrogen bonding with Tyr 385, Ser 530, Tyr 467, and Tyr 158 amino acid residues, respectively. The novel compounds are active antibacterial agents with potential inhibition on E. coli bacteria. The toxicity results showed good percentage viability of human kidney cell lines with IC50 value greater than 100 µg/cm3 concentration. The Hirshfeld surface analysis and electrostatic potential map of compound showed good intermolecular contacts and hydrogen bonding donor and acceptor potential.

Graphic abstract

Keywords

Michael addition Alkynes Carbonyl compounds Protein Hydrothiolation Toxicity 

Notes

Acknowledgements

The authors are grateful to NGSM Institute of Pharmaceutical Sciences Nitte (Deemed to be University) for carrying out animal studies and USIC Mangalore University for spectral data.

Supplementary material

706_2019_2507_MOESM1_ESM.docx (1.4 mb)
Supplementary material 1 (DOCX 1398 kb)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of ChemistryMangalore UniversityMangalagangothriIndia
  2. 2.Department of Materials ScienceMangalore UniversityMangalagangothriIndia
  3. 3.Department of Chemical SciencesIISERMohaliIndia

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