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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

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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.

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References

  1. Rajak H, Kharya M, Mishra P (2007) Yakugaku Zasshi 127:1757

    Article  CAS  Google Scholar 

  2. Vane JR (1971) Nature 231:232

    CAS  Google Scholar 

  3. Vane JR, Bakhle Y, Botting R (1998) Annu Rev Pharmacol Toxicol 38:97

    Article  CAS  Google Scholar 

  4. Abdel-Aziz AAM, Abou-Zeid LA, ElTahir KEH, Ayyad RR, El-Sayed MAA, El-Azab AS (2016) Eur J Med Chem 121:410

    Article  CAS  Google Scholar 

  5. Omar FA, Mahfouz NM, Rahman MA (1996) Eur J Med Chem 31:819

    Article  CAS  Google Scholar 

  6. Shetgiri NP, Nayak BK (2005) Indian J Chem B 44:1267

    Google Scholar 

  7. Golgolab H, Lalezari I, Hosseini L, Hosseini-Gohari L (1973) J Heterocycl Chem 10:387

    Article  CAS  Google Scholar 

  8. Singh AK, Lohani M, Parthsarathy R (2013) Iran J Pharm Res 12:319

    CAS  Google Scholar 

  9. Jayashankar B, Rai KML, Baskaran N, Sathish HS (2009) Eur J Med Chem 44:3898

    Article  CAS  Google Scholar 

  10. Arshad M (2014) Int J Pharm Sci Res 5:1124

    Google Scholar 

  11. Akhter M, Husain A, Azad B, Ajmal M (2009) Eur J Med Chem 44:2372

    Article  CAS  Google Scholar 

  12. Bharathi D, Hemalatha S, Devadas G, Kumar PR, Shanmugasundaram P, Aanandhi MV (2010) Int J Chemtech Res 2:1867

    CAS  Google Scholar 

  13. Biá-Ventura TL, Calixto SD, Vieira B, D’Souza AMT, Mello MVP, Rodrigues CR, Miranda LS, D’Souza ROMA, Leal ICR, Lasunskaia EB, Muzitano MF (2015) Molecules 20:8072

    Article  Google Scholar 

  14. Thwaites G, Fisher M, Hemingway C, Scott G, Solomon T (2009) J Infect 59:167

    Article  Google Scholar 

  15. Jha KK, Samad A, Kumar Y, Shaharyar M, Khosa R, Jain J, Bansal S (2009) Iran J Pharm Res 8:163

    CAS  Google Scholar 

  16. Tatar E, Karakus S, Kucukguzel SG, Okullu SO, Unubol N, Kocagoz T, De Clercq E, Andrei G, Snoeck R, Pannecouque C, Kalayci S, Sahin F, Sriram D, Yogeeswari P, Kucukguzel I (2016) Biol Pharm Bull 39:502

    Article  CAS  Google Scholar 

  17. Krasavin M, Lukin A, Vedekhina T, Manicheva O, Dogonadze M, Vinogradova T, Zabolotnykh N, Rogacheva E, Kraeva L, Sharoyko V, Tennikova TB, Dar’in D, Sokolovich E (2019) Eur J Med Chem 166:125

    Article  CAS  Google Scholar 

  18. Ramaprasad GC, Kalluraya B, Kumar BS, Hunnur RK (2010) Eur J Med Chem 45:4587

    Article  CAS  Google Scholar 

  19. Kalluraya B, Aamir S, Shabaraya AR (2012) Eur J Med Chem 54:597

    Article  Google Scholar 

  20. Girisha KS, Kalluraya B, Narayana V (2010) Eur J Med Chem 45:4640

    Article  CAS  Google Scholar 

  21. Isloor AM, Kalluraya B, Pai KS (2010) Eur J Med Chem 45:825

    Article  CAS  Google Scholar 

  22. Movassagh B, Shaygan P (2006) Ark Online J Org Chem 12:130

    Google Scholar 

  23. Omar MT, Basyouni MN (1974) Bull Chem Soc Jpn 47:2325

    Article  CAS  Google Scholar 

  24. Brenton AG, Godfrey AR (2010) J Am Soc Mass Spectrom 21:1821

    CAS  PubMed  Google Scholar 

  25. Wolff SK, Grimwood DJ, McKinnon JJ, Jayatilaka D, Spackman MA (2007) Crystal Explorer 3.0, University of Western Australia, Perth, Australia

  26. Spackman MA, McKinnon J (2002) J Cryst Eng Commun 4:378

    Article  CAS  Google Scholar 

  27. Soman R, Sujatha S, Arunkumar C (2014) J Fluorine Chem 163:16

    Article  CAS  Google Scholar 

  28. Spackman MA, McKinnon JJ, Jayatilaka D (2008) CrystEngComm 10:377

    CAS  Google Scholar 

  29. Winter CA, Risely EA, Nuss GW (1962) Proc Soc Exp Biol 111:544

    Article  CAS  Google Scholar 

  30. Collins LA, Franzblau SG (1997) Antimicrob Agents Chemother 41:1004

    Article  CAS  Google Scholar 

  31. He X, Alian A, Stroud R, de Montellano PRO (2006) J Med Chem 49:6308

    Article  CAS  Google Scholar 

  32. Ansari FL, Nazir S, Noureen H, Miraza B (2005) Chem Biodivers 2:1656

    Article  CAS  Google Scholar 

  33. Mosmann T (1983) J Immunol Methods 65:55

    Article  CAS  Google Scholar 

  34. Balakrishna K (1987) Synthesis, characterization and biological activities of some nitrofuran and oxadiazole derivatives. PhD Thesis, Mangalore University, India

  35. Alphonsus D (1994) Some contributions to the chemistry of nitrogen and sulphur containing heterocycles. PhD Thesis, Mangalore University, India

  36. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) J Comput Chem 16:2785

    Article  Google Scholar 

  37. Sidhu RS, Lee JY, Yuan C, Smith WL (2010) Biochemistry 49:7069

    Article  CAS  Google Scholar 

  38. Rowlinson SW, Keifer JR, Prusakiewicz JJ, Pawlitz JL, Kozak KR, Kalgutkar AS, Stallings WC, Kurumbail RG, Marnett LJ (2003) J Biol Chem 278:45763

    Article  CAS  Google Scholar 

  39. Gilbert NC, Bartlet SG, Waight MT, Neau DB, Boeglin WE, Brash AR, Newcomer ME (2011) Science 331:217

    Article  CAS  Google Scholar 

  40. Schuttelkopf AW, van Aalten DMF (2004) Acta Crystallogr D Biol Crystallogr 60:1355

    Article  Google Scholar 

  41. The PyMOL Molecular Graphics System, Version 2.0. Schrondinger, LLC

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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.

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Authors and Affiliations

  1. Department of Chemistry, Mangalore University, Mangalagangothri, 574199, India

    Vishwanath Turukarabettu & Balakrishna Kalluraya

  2. Department of Materials Science, Mangalore University, Mangalagangothri, 574199, India

    Vishwanath Turukarabettu

  3. Department of Chemical Sciences, IISER, Mohali, 140306, India

    Monika Sharma

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  1. Vishwanath Turukarabettu
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  2. Balakrishna Kalluraya
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  3. Monika Sharma
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Correspondence to Balakrishna Kalluraya.

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Turukarabettu, V., Kalluraya, B. & Sharma, M. 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. Monatsh Chem 150, 1999–2010 (2019). https://doi.org/10.1007/s00706-019-02507-2

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