Skip to main content
SpringerLink
Log in

Design and synthesis of novel thiopheno-4-thiazolidinylindoles as potent antioxidant and antimicrobial agents

  • Original Paper
  • Published:
Chemical Papers Aims and scope Submit manuscript

Abstract

A novel and convenient synthesis of thiopheno-4-thiazolidinyl indole analogues is presented (IVa-IVi), with the aim of obtaining biologically active compounds. 3,5-disubstituted indol-2-carboxyhydrazides (Ia-If) were allowed to react with 3-acetyl-2,5-dichlorothiophene (II) to yield the corresponding 3,5-disubstituted indol-2-carbohydrazides (IIIa-IIIf). The pre-formed indolecarbohydrazides (IIIa-IIIf) were allowed to react with 2-mercaptoacetic acid or 2-mercaptopropanoic acid to produce thiopheno-4-thiazolidinylindoles (IVa-IVi). This reaction protocol affords a simple, eco-friendly, non-hazardous, easier preparation and high yields. The antioxidant (free radical scavenging, total antioxidant capacity and ferric-reducing antioxidant power) and antimicrobial activities of the synthesised compounds were evaluated. The structures and purity of the products were confirmed by their IR, 1H NMR, 13C NMR and mass spectral and analytical data. Most of the compounds tested showed very significant scavenging, antioxidant and antimicrobial activities. Compounds containing electron donor group (CH3) at the fifth position of indole exhibit an excellent ferric-reducing activity. The present study suggests that compounds IIIa-IIIb, IIIf, IVa-IVc, IVf-IVi, may serve as promising lead scaffolds for antioxidant and antimicrobial agents.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ames, B. N. (1983). Dietary carcinogens and anticarcinogens: Oxygen radicals and degenerative diseases. Science, 221, 1256–1264. DOI: 10.1126/science.6351251.

    Article  CAS  Google Scholar 

  • BaMaung, N. Y., Craig, R. A., Kawai, M., & Wang, J. (2001). 3-substituted indole angiogenesis inhibitors. U. S. Patent No. 6,323,228. Washington, DC, USA: Patent and Trademark Office.

    Google Scholar 

  • Barreca, M. L., Chimirri, A., De Luca, L., Monforte, A. M., Monforte, P., Rao, A., Zappalà, M., Balzarini, J., De Clercq, E., Pannecouque, C., & Witvrouw, M. (2001). Discovery of 2,3-diaryl-1,3-thiazolidin-4-ones as potent anti-HIV-1 agents. Bioorganic & Medicinal Chemistry Letters, 11, 1793–1796. DOI: 10.1016/s0960-894x(01)00304-3.

    Article  CAS  Google Scholar 

  • Barreira, J. C. M., Ferreira, I. C. F. R., Oliveira, M. B. P. P., & Pereira, J. A. (2008). Antioxidant activity and bioactive compounds of ten Portuguese regional and commercial almond cultivars. Food and Chemical Toxicology, 46, 2230–2235. DOI: 10.1016/j.fct.2008.02.024.

    Article  CAS  Google Scholar 

  • Biradar, J. S., & Manjunath, S. Y. (2004). Synthesis and biological activities of novel 2-(5′-substituted-3′ phenylindole-2′-yl)-1,3,4-oxadiazino[5,6-b] indole 3-(5′-substituted-3′-phenylindole-2′-amido) spiro (indol-3″,2,thiazolidin)-2″,4-diones. Indian Journal of Chemistry Section B, 43, 389–392.

    Google Scholar 

  • Biradar, J. S., Sasidhar, B. S., & Parveen, R. (2010). Synthesis, antioxidant and DNA cleavage activities of novel indole derivatives. European Journal of Medicinal Chemistry, 45, 4074–4078. DOI: 10.1016/j.ejmech.2010.05.067.

    Article  CAS  Google Scholar 

  • Biradar, J. S., & Sasidhar, B. S. (2011). Solvent-free, microwave assisted Knoevenagel condensation of novel 2,5-disubstituted indole analogues and their biological evaluation. European Journal of Medicinal Chemistry, 46, 6112–6118. DOI: 10.1016/j.ejmech.2011.10.004.

    Article  CAS  Google Scholar 

  • Blois, M. S. (1958). Antioxidant determinations by the use of a stable free radical. Nature, 181, 1199–1200. DOI: 10.1038/1811199a0.

    Article  CAS  Google Scholar 

  • Bonde, C. G., & Gaikwad, N. J. (2004). Synthesis and preliminary evaluation of some pyrazine containing thiazolines and thiazolidinones as antimicrobial agents. Bioorganic & Medicinal Chemistry, 12, 2151–2161. DOI: 10.1016/j.bmc.2004.02.024.

    Article  CAS  Google Scholar 

  • Curcio, M., Puoci, F., Iemma, F., Parisi, O. I., Cirillo, G., Spizzirri, U. G., & Picci, N. (2009). Covalent insertion of antioxidant molecules on chitosan by a free radical grafting procedure. Journal of Agricultural and Food Chemistry, 57, 5933–5938. DOI: 10.1021/jf900778u.

    Article  CAS  Google Scholar 

  • Estevão, M. S., Carvalho, L. C., Ribeiro, D., Couto, D., Freitas, M., Gomes, A., Ferreira, L. M., Fernandes, E., & Marques, M. M. B. (2010). Antioxidant activity of unexplored indole derivatives: Synthesis and screening. European Journal of Medicinal Chemistry, 45, 4869–4878. DOI: 10.1016/j.ejmech.2010.07.059.

    Article  Google Scholar 

  • Francis, J. S., Doherty, M. C., Lopatin, U., Johnston, C. P., Sinha, G., Ross, T., Cai, M., Hansel, N. N., Perl, T., Ticehurst, J. R., Carroll, K., Thomas, D. L., Nuermberger, E., & Barlett, G. (2005). Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes. Clinical Infectious Diseases, 40, 100–107. DOI: 10.1086/427148.

    Article  Google Scholar 

  • Hadjipavlou-Litina, D., Magoulas, G. E., Bariamis, S. E., Drainas, D., Avgoustakis, K., & Papaioannou, D. (2010). Does conjugation of antioxidants improve their antioxidative/anti-inflammatory potential?. Bioorganic & Medicinal Chemistry, 18, 8204–8217. DOI: 10.1016/j.bmc.2010.10.012.

    Article  CAS  Google Scholar 

  • Havrylyuk, D., Zimenkovsky, B., Vasylenko, O., Zaprutko, L., Gzella, A., & Lesyk, R. (2009). Synthesis of novel thiazolonebased compounds containing pyrazoline moiety and evaluation of their anticancer activity. European Journal of Medicinal Chemistry, 44, 1396–1404. DOI: 10.1016/j.ejmech.2008.09.032.

    Article  CAS  Google Scholar 

  • Jenner, P., & Olanow, C. W. (1996). Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology, 47, 161–170. DOI: 10.1212/wnl.47.6 suppl 3.161s.

    Article  Google Scholar 

  • Kataoka, M., Tonooka, K., Ando, T., Imai, K., & Aimoto, T. (1997). Hydroxyl radical scavenging activity of nonsteroidal anti-inflammatory drugs. Free Radical Research, 27, 419–427. DOI: 10.3109/10715769709065781.

    Article  CAS  Google Scholar 

  • Khan, S. A., Asiri, A. M., & Yusuf, M. (2009). Synthesis and biological evaluation of some thiazolidinone derivatives of steroid as antibacterial agents. European Journal of Medicinal Chemistry, 44, 2597–2600. DOI: 10.1016/j.ejmech.2009.04.032.

    Article  CAS  Google Scholar 

  • Koleva, I. I., van Beek, T. A., Linssen, J. P. H., de Groot, A., & Evstatieva, L. N. (2002). Screening of plant extracts for antioxidant activity: a comparative study of three testing methods. Phytochemical Analysis, 13, 8–17. DOI: 10.1002/pca.611.

    Article  CAS  Google Scholar 

  • Mohareb, R. M., Ahmed, H. H., Elmegeed, G. A., Abd-Elhalim, M. M., & Shafic, R. W. (2011). Development of new indole-derived neuroprotectiveagents. Bioorganic & Medicinal Chemistry, 19, 2966–2974. DOI: 10.1016/j.bmc.2011.03.031.

    Article  CAS  Google Scholar 

  • Park, J. Y., Kim, E. J., Kwon, K. J., Jung, Y. S., Moon, C. H., Lee, S. H., & Baik, E. J. (2004). Neuroprotection by fructose-1,6-bisphosphate involves ROS alterations via p38 MAPK/ERK. Brain Research, 1026, 295–301. DOI: 10.1016/j.brainres.2004.08.039.

    Article  CAS  Google Scholar 

  • Praveen, C., Ayyanar, A., & Perumal, P. T. (2011). Practical synthesis, anticonvulsant and antimicrobial activity of N-allyl and N-propargyl di(indolyl)indolin-2-ones. Bioorganic & Medicinal Chemistry Letters, 21, 4072–4077. DOI: 10.1016/j.bmcl.2011.04.117.

    Article  CAS  Google Scholar 

  • Saenjum, C., Chaiyasut, C., Kadchumsang, S., Chansakaow, S., & Suttajit, M. (2010). Antioxidant activity and protective effects on DNA damage of Caesalpinia sappan L. extract. Journal of Medicinal Plants Research, 4, 1594–1600. DOI: 10.5897/jmpr10.080.

    Google Scholar 

  • Simonian, N. A., & Coyle, J. T. (1996). Oxidative stress in neurodegenerative diseases. Annual Review of Pharmacology Toxicology, 36, 83–106. DOI: 10.1146/annurev.pa.36.040196.000503.

    Article  CAS  Google Scholar 

  • Singh, R. P., Murthy, K. N. C., & Jayaprakasha, G. K. (2002). Studies on the antioxidant activity of pomegranate (Punica granatum) peel and seed extracts using in vitro models. Journal of Agricultural and Food Chemistry, 50, 81–86. DOI: 10.1021/jf010865b.

    Article  CAS  Google Scholar 

  • Squadrito, G. L., & Pryor, W. A. (1998). Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite and carbon dioxide. Free Radical Biology and Medicine, 25, 392–403. DOI: 10.1016/s0891-5849(98)00095-1.

    Article  CAS  Google Scholar 

  • Süzen, S. (2007). Antioxidant activities of synthetic indole derivatives and possible activity mechanisms. Topics in Heterocyclic Chemistry, 11, 145–178. DOI: 10.1007/7081 2007074.

    Article  Google Scholar 

  • Valko, M., Rhodes, C. J., Moncol, J., Izakovic, M., & Mazur, M. (2006). Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chemico-Biological Interactions, 160, 1–40. DOI: 10.1016/j.cbi.2005.12.009.

    Article  CAS  Google Scholar 

  • Vicini, P., Geronikaki, A., Anastasia, K., Incerti, M., & Zani, F. (2006). Synthesis and antimicrobial activity of novel 2-thiazolylimino-5-arylidene-4-thiazolidinones. Bioorganic & Medicinal Chemistry, 14, 3859–3864. DOI: 10.1016/j.bmc.2006.01.043.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Central Research Lab, Department of Chemistry, Gulbarga University, Gulbarga, 585 106, Karnataka State, India

    Jaiprakash S. Biradar, Parveen Rajesab & B. Somappa Sasidhar

  2. Organic Chemistry Section, Chemical Sciences & Technology Division, National Institute for Interdisciplinary Science and Technology (CSIR), Thiruvananthapuram, 695 019, Kerala State, India

    B. Somappa Sasidhar

Authors
  1. Jaiprakash S. Biradar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Parveen Rajesab
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Somappa Sasidhar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jaiprakash S. Biradar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Biradar, J.S., Rajesab, P. & Sasidhar, B.S. Design and synthesis of novel thiopheno-4-thiazolidinylindoles as potent antioxidant and antimicrobial agents. Chem. Pap. 68, 392–400 (2014). https://doi.org/10.2478/s11696-013-0452-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2478/s11696-013-0452-3

Keywords

Search

Navigation