SpringerLink
Log in

Synthesis of spirooxindolocarbamates based on Betti reaction: antibacterial, antifungal and antioxidant activities

  • Original Article
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

A series of new spirooxindolocarbamates 4a–l and 6a–d were synthesized by using the Betti reaction. All the target compounds were well characterized by IR, NMR and mass spectrometry. The structures of the compounds 4a and 4e were confirmed by the single crystal X-ray diffraction. The in vitro antibacterial activity results revealed that the compounds 4f exhibited excellent antibacterial activity against E. coli with MIC value 7.5 µg/mL when compared with the standard drug ciprofloxacin with MIC value 9.25 µg/mL. The compounds 4l and 6c exhibit significant inhibiting activity against E. Coli with MIC values 10.5 µg/mL and 9.5 µg/mL, respectively. The compounds 4c and 4e showed significant activity against S. aureus with MIC value 10.5 µg/mL. The compounds 4a and 4f were exhibited moderate antifungal activity against A. niger with MIC values 17.5 µg/mL and 18.0 µg/mL, respectively. The compounds 4f and 4l exhibited the potent antioxidant activity with IC50 values 9.12 ± 0.01 µM and 7.06 ± 0.78 µM, respectively.

Graphic abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Scheme 2
Fig. 2

Similar content being viewed by others

References

  1. Dandia A, Khan S, Soni P, Indora A, Mahawar DK, Pandya P, Chauhan CS (2017) Diversity-oriented sustainable synthesis of antimicrobial piropyrrolidine/thiapyrrolizidine oxindole derivatives: new ligands for a metallo-b-lactamase from Klebsiella pneumonia. Bioorg Med Chem Lett 27:2873–2880. https://doi.org/10.1016/j.bmcl.2017.04.083

    Article  CAS  Google Scholar 

  2. Arun Y, Saranraj K, Balachandran C, Perumal PT (2014) Anticancer activity of ruthenocenyl chalcones and their molecular docking studies. Eur J Med Chem 74:50–64. https://doi.org/10.1016/j.ejmech.2013.12.027

    Article  CAS  Google Scholar 

  3. Nabid MR, Rezaei SJT, Ghahremanzadeh R, Bazgir A (2010) Ultrasound-assisted one-pot, three-component synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones. Ultrason Sonochem 17:159–161. https://doi.org/10.1016/j.ultsonch.2009.06.012

    Article  CAS  Google Scholar 

  4. Sridharan V, Karthikeyan K, Muthusubramanian S (2006) Unexpected multicomponent reaction of 2/4-methoxyarylaldehydes with arylhydroxylamines and maleic anhydride: a novel synthesis of unsymmetrical diarylamines. Tetrahedron Lett 47:4221–4223. https://doi.org/10.1016/j.tetlet.2006.04.043

    Article  CAS  Google Scholar 

  5. Nishtala VB, Nanubolu JB, Basavoju S (2017) Ultrasound-assisted rapid and efficient one-pot synthesis of furanyl spirooxindolo and spiroquinoxalinopyrrolizidines by 1,3-dipolar cycloaddition: a green protocol. Res Chem Intermed 43:1365–1381. https://doi.org/10.1007/s11164-016-2703-8

    Article  CAS  Google Scholar 

  6. Singh GS, Desta ZY (2012) Isatins as privileged molecules in design and synthesis of spiro-fused cyclic frameworks. Chem Rev 112:6104–6155. https://doi.org/10.1021/cr300135y

    Article  CAS  Google Scholar 

  7. Chandam DR, Patravale AA, Jadhav SD, Deshmukh MB (2017) Low melting oxalic acid dihydrate: proline mixture as dual solvent/catalyst for synthesis of spiro[indoline-3,9′-xanthene]trione and dibarbiturate derivatives. J Mol Liq 240:98–105. https://doi.org/10.1016/j.molliq.2017.05.070

    Article  CAS  Google Scholar 

  8. Barakat A, Islam MS, Ghawas HM, Majid AMA, Senduny FFE, Badria FA, Elshaier YAMM, Ghabbour HA (2019) Design and synthesis of new substituted spirooxindoles as potential inhibitors of the MDM2–p53 interaction. Bioorg Chem 86:598–608

    Article  CAS  Google Scholar 

  9. Pogaku V, Krishna VS, Sriram D, Rangan K, Basavoju S (2019) Ultrasonication-ionic liquid synergy for the synthesis of new potent anti-tuberculosis 1,2,4-triazol-1-yl-pyrazole based spirooxindolopyrrolizidines. Bioorg Med Chem Lett. https://doi.org/10.1016/j.bmcl.2019.04.026

    Article  Google Scholar 

  10. Chandralekha E, Thangamani A, Valliappan R (2013) Ultrasound-promoted regioselective and stereoselective synthesis of novel spiroindanedionepyrrolizidines by multicomponent 1,3-dipolar cycloaddition of azomethine ylides. Res Chem Intermed 39:961–972. https://doi.org/10.1007/s11164-012-0608-8

    Article  CAS  Google Scholar 

  11. Chen G, Yang J, Gao S, Zhang Y, Hao X (2015) Theoretical study of regioselectivity in the synthesis of spiro [pyrrolidine-2,3′-oxindole] compounds by [3 + 2] cycloaddition. Res Chem Intermed 41:4987–4996. https://doi.org/10.1007/s11164-014-1582-0

    Article  CAS  Google Scholar 

  12. Dibenedetto A, Aresta M, Fragale C, Narracci M (2002) Reaction of silylalkylmono- and silylalkyldi-amines with carbon dioxide: evidence of formation of inter- and intra-molecular ammonium carbamates and their conversion into organic carbamates of industrial interest under carbon dioxide catalysis. Green Chem 4:439–443. https://doi.org/10.1039/B205319P

    Article  CAS  Google Scholar 

  13. Gupte SP, Shivarkar AB, Chaudhari PV (2001) Carbamate synthesis by solid-base catalyzed reaction of disubstituted ureas and carbonates. Chem Commun 24:2620–2621. https://doi.org/10.1039/B107947F

    Article  Google Scholar 

  14. Martin LL, Davis L, Klein JT, Nemoto P, Olsen GE, Bores GM, Camacho F, Petko WW, Rush DK, Selk D, Smith CP, Vargas HM, Winslow JT, Effland RC, Fink DM (1997) Synthesis and preliminary structure-activity relationships of 1-[(3-fluoro-4-pyridinyl)amino]-3-methyl-1H-indol-5-yl methyl carbamate (p10358), a novel acetylcholinesterase inhibitor. Bioorg Med Chem Lett 7:157–162. https://doi.org/10.1016/S0960-894X(96)00592-6

    Article  CAS  Google Scholar 

  15. Vagner J, Qu H, Hruby VJ (2008) Peptidomimetics, a synthetic tool of drug discovery. Curr Opin Chem Biol 12:292–296. https://doi.org/10.1016/j.cbpa.2008.03.009

    Article  CAS  Google Scholar 

  16. Nowick JS (2006) What I have learned by using chemical model systems to study biomolecular structure and interactions. Org Biomol Chem 4:3869–3885. https://doi.org/10.1039/B608953B

    Article  CAS  Google Scholar 

  17. Liskamp RM, Rijkers DT, Kruijtzer JA, Kemmink J (2011) Peptides and proteins as a continuing exciting source of inspiration for peptidomimetics. Chem Bio Chem 12:1626–1653. https://doi.org/10.1002/cbic.201000717

    Article  CAS  Google Scholar 

  18. Cho CY, Moran EJ, Cherry SR, Stephans JC, Fodor SP, Adama CL, Sundaram A, Jacobs JW, Schultz PG (1993) An unnatural biopolymer. Science 261:1303–1305. https://doi.org/10.1126/science.7689747

    Article  CAS  Google Scholar 

  19. Ghosh AK, Brindisi M (2015) Organic carbamates in drug design and medicinal chemistry. J Med Chem 58:2895–2940. https://doi.org/10.1021/jm501371s

    Article  CAS  Google Scholar 

  20. Mousa SA, DeGrado WF, Mu DX, Kapil RP, Lucchesi BR, Reilly TM (1996) Oral antiplatelet, antithrombotic efficacy of DMP 728, a novel platelet GPIIb/IIIa antagonist. Circulation 93:537–543. https://doi.org/10.1161/01.CIR.93.3.537

    Article  CAS  Google Scholar 

  21. Xue CB, Wityak J, Sielecki TM, Pinto DJ, Batt DG, Cain GA, Sworin M, Rockwell AL, Roderick JJ, Wang S, Orwat MJ, Frietze WE, Bostrom LL, Liu J, Higley CA, Rankin FW, Tobin AE, Emmett G, Lalka GK, Sze JY, Meo SVD, Mousa SA, Thoolen MJ, Racanelli AL, Hausner EA, Reilly TM, DeGrado WF, Wexler RR, Olson RE (1997) Discovery of an orally active series of isoxazoline glycoprotein IIb/IIIa antagonists. J Med Chem 40:2064–2084. https://doi.org/10.1021/jm960799i

    Article  CAS  Google Scholar 

  22. Saito A, Yamashita T, Mariko Y, Nosaka Y, Tsuchiya K, Ando T, Suzuki T, Tsuruo T, Nakanishi O (1999) A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. Proc Natl Acad Sci USA 96:4592–4597

    Article  CAS  Google Scholar 

  23. Williams BR, Nazarians A, Gill MA (2003) A review of rivastigmine: a reversible cholinesterase inhibitor. Clin Ther 25:1634–1653. https://doi.org/10.1016/S0149-2918(03)80160-1

    Article  CAS  Google Scholar 

  24. Emre M, Aarsland D, Albanese A, Byrne EJ, Deusch G, Deyn PPD, Durif F, Kulisevsky J, Laar TV, Lees A, Poewe W, Robillard A, Rosa MM, Wolters E, Quarg P, Tekin S, Lane R (2004) Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med 351:2509–2518. https://doi.org/10.1056/NEJMOA041470

    Article  CAS  Google Scholar 

  25. Best BM, Goicoechea M (2008) Efavirenz—still first-line king? Exp Opin Drug Metab Toxicol 4:965–972. https://doi.org/10.1517/17425255.4.7.965

    Article  CAS  Google Scholar 

  26. Madero JS, Keever AV, Mendez P, Gomez JLM, Escobar IT, Escolano FG, Kasusky IJ, Aquino MM, Santos CR, Saleme LP, Frausto SR, Puente BA, Ramirez LES, Lima V, Zamudio FB, Ramirez BC, Montaner J (2010) Prospective, randomized, open label trial of Efavirenz vs Lopinavir/Ritonavir in HIV + treatment-naive subjects With CD4 + <200 cell/mm3 in Mexico. J Acquir Immune Defic Syndr 53:582–588. https://doi.org/10.1097/QAI.0b013e181cae4a1

    Article  Google Scholar 

  27. Phipatanakul W, Eggleston PA, Walker CMK, Kesavanathan J, Sweitzer D, Wood RA (2000) A randomized, double-blind, placebo-controlled trial of the effect of zafirlukast on upper and lower respiratory responses to cat challenge. J Allergy Clin Immunol 105:704–710. https://doi.org/10.1067/mai.2000.105123

    Article  CAS  Google Scholar 

  28. Yoshida M, Hara N, Okuyama S (2000) Catalytic production of urethanes from amines and alkyl halides in supercritical carbon dioxide. Chem Commun 2:151–152. https://doi.org/10.1039/A908819l

    Article  Google Scholar 

  29. Salvatore RN, Chu FX, Nagle AS, Kapxhiu EA, Cross RM, Jung KW (2002) Efficient Cs2CO3-promoted solution and solid phase synthesis of carbonates and carbamates in the presence of TBAI. Tetrahedron 58:3329–3347. https://doi.org/10.1016/S0040-4020(02)00286-7

    Article  CAS  Google Scholar 

  30. Scriven EFV, Turnbull K (1988) Azides: their preparation and synthetic uses. Chem Rev 88:297–368. https://doi.org/10.1021/cr00084a001

    Article  CAS  Google Scholar 

  31. Gogoi P, Konwar D (2007) An efficient modification of the Hofmann rearrangement: synthesis of methyl carbamates. Tetrahedron Lett 48:531–533. https://doi.org/10.1016/j.tetlet.2006.11.134

    Article  CAS  Google Scholar 

  32. Cenini S, Crotti C, Pizzotti M, Porta F (1988) Ruthenium carbonyl catalyzed reductive carbonylation of aromatic nitro compounds. A selective route to carbamates. J Org Chem 53:1243–1250. https://doi.org/10.1021/jo00241a023

    Article  CAS  Google Scholar 

  33. Salvatore RN, Ledger JA, Jung KW (2001) An efficient one-pot synthesis of N-alkyl carbamates from primary amines using Cs2CO3. Tetrahedron Lett 42:6023–6025. https://doi.org/10.1016/S0040-4039(01)01198-4

    Article  CAS  Google Scholar 

  34. Nishtala VB, Basavoju S (2018) Crystal structure and molecular docking studies of 1-ethyl-2′-(furan-2-carbonyl)-1′-(furan-2-yl)-1′,2′,5′,6′,7′,7a′-hexahydrospiro[indoline-3,3′-pyrrolizin]-2-one. J Chem Crystallogr 48:78–90. https://doi.org/10.1007/s10870-018-0709-3(References therein)

    Article  CAS  Google Scholar 

  35. Bauer AW, Kirby WM, Sherris JC, Turck M (1996) Antibiotic susceptibility testing by a standardized single dist method. Am J Clin Pathol 45:493–495. https://doi.org/10.1093/ajcp/45.4_ts.493

    Article  Google Scholar 

  36. Braca A, Tommasi ND, Bari LD, Pizza C, Politi M, Morelli I (2001) Antioxidant principles from Bauhinia tarapotensis. J Nat Prod 64:892–895. https://doi.org/10.1021/np0100845

    Article  CAS  Google Scholar 

  37. Blois MS (1958) Antioxidant determinations by the use of a stable free radical. Nature 181:1199–1200. https://doi.org/10.1038/1811199a0

    Article  CAS  Google Scholar 

Download references

Acknowledgements

S.B. thanks the Council of Scientific and Industrial Research (CSIR, India) [02(0300)/17/EMR-II] for financial support. The authors S. B. and V. B. N. thank the Director, National Institute of Technology, Warangal for providing research facilities. V. B. N. thanks the MHRD for providing research fellowship.

Author information

Authors and Affiliations

  1. Department of Chemistry, National Institute of Technology Warangal, Warangal, Telangana, 506 004, India

    Venkata Bharat Nishtala & Srinivas Basavoju

  2. Natural Products Division, Department of Chemistry, Osmania University, Hyderabad, Telangana, 500 007, India

    Chityala Mahesh & Vijay Kumar Pasala

  3. School of Chemistry, University of Hyderabad, Gachibowli, Hyderabad, Telangana, 500 046, India

    G. Bhargavi

Authors
  1. Venkata Bharat Nishtala
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chityala Mahesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Bhargavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vijay Kumar Pasala
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Srinivas Basavoju
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Srinivas Basavoju.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

11030_2019_10017_MOESM1_ESM.docx

It contains the experimental section, crystal structure analysis, characterization data and copies of spectra (IR, NMR and Mass) and protocols of the biological activities (DOCX 8774 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nishtala, V.B., Mahesh, C., Bhargavi, G. et al. Synthesis of spirooxindolocarbamates based on Betti reaction: antibacterial, antifungal and antioxidant activities. Mol Divers 24, 1139–1147 (2020). https://doi.org/10.1007/s11030-019-10017-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-019-10017-w

Keywords

Search

Navigation