Skip to main content
SpringerLink
Log in

Synthesis, pharmacophore modeling, and cytotoxic activity of 2-thioxothiazolidin-4-one derivatives

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

A series of 2-thioxothiazolidin-4-one derivatives were efficiently synthesized and evaluated for their cytotoxic activity against four tumor cell lines. The synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR, and mass spectral data. Compound 5c exhibited notable in vitro anticancer activity against HeLa, HT29, A549, and MCF-7 cell lines with IC50 values of 28.3, 24.5, 26.6, and 28.6 µM, respectively. Common pharmacophore model with H bond donor (2), H bond acceptor (3), Hydrophobic (1), and ring aromatic (2) was developed using phase module, and molecular docking of target compounds into the epidermal growth factor receptor kinase revealed important structural information on the plausible binding interactions.

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

Fig. 1
Scheme 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Alegaon SG, Alagawadi KR, Sonkusare PV, Chaudhary SM, Dadwe DH, Shah AS (2012) Novel imidazo[2,1-b][1,3,4]thiadiazole carrying rhodanine-3-acetic acid as potential antitubercular agents. Bioorg Med Chem Lett 22:1917–1921

    Article  CAS  PubMed  Google Scholar 

  • Azizmohammadi M, Khoobi M, Ramazani A, Emami S, Zarrin A, Firuzi O, Miri R, Shafiee A (2013) 2H-Chromene derivatives bearing thiazolidine-2,4-dione, rhodanine or hydantoin moieties as potential anticancer agents. Eur J Med Chem 59:15–22

    Article  CAS  PubMed  Google Scholar 

  • Bois F, Boumendjel A, Mariotte A, Conseil G, Di Petro A (1999) Synthesis and biological activity of 4-alkoxy chalcones: potential hydrophobic modulators of p-glycoprotein-mediated multidrug resistance. Bioorg Med Chem 7:2691–2695

    Article  CAS  PubMed  Google Scholar 

  • Chan H, Fan YH, Natarajan A, Guo Y, Iyasere J, Harbinski F, Luus L, Christ W, Aktas H, Halperin JA (2004) Synthesis and biological evaluation of thiazolidine-2,4-dione and 2,4-thione derivatives as inhibitors of translation initiation. Bioorg Med Chem Lett 15:5401–5405

    Article  Google Scholar 

  • Chandrappa S, Kavitha CV, Shahabuddin MS, Vinaya K, Anand Kumar CS, Ranganath SR, Raghavan SC, Rangappa KS (2009) Synthesis of 2-(5-((5-(4-chlorophenyl)furan-2-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid derivatives and evaluation of their cytotoxicity and induction of apoptosis in human leukemia cells. Bioorg Med Chem 17:2576–2584

    Article  CAS  PubMed  Google Scholar 

  • Cutshall NS, O’Day C, Prezhdo M (2005) Rhodanine derivatives as inhibitors of JSP-1. Bioorg Med Chem Lett 15:3374–3379

    Article  CAS  PubMed  Google Scholar 

  • Dixon SL, Smondyrev AM, Knoll EH, Rao SN, Shaw DE, Friesner RA (2006) PHASE: a new enzyme for pharmacophore perception, 3D QSAR model development, and 3D database screening. 1. Methodology and preliminary results. J Comput Aided Mol Des 20:647–671

    Article  CAS  PubMed  Google Scholar 

  • Fadeyi OO, Adamson ST, Myles EL, Okoro CO (2008) Novel fluorinated acridone derivatives. Part 1: synthesis and evaluation as potential anticancer agents. Bioorg Med Chem Lett 18:4172–4176

    Article  CAS  PubMed  Google Scholar 

  • Go ML (2003) Novel antiplasmodial agents. Med Res Rev 23:456–487

    Article  CAS  PubMed  Google Scholar 

  • Go ML, Wu X, Liu XL (2005) Chalcones: an update on cytotoxic and chemoprotective properties. Curr Med Chem 12:481–499

    Article  CAS  PubMed  Google Scholar 

  • Hardej D, Ashby CR Jr, Khadtare NS, Kulkarni SS, Singh S, Talele T (2010) The synthesis of phenylalanine-derived C5-substuted rhodanines and their activity against selected methicillin-resistant staphylococcus aureus (MRSA) strains. Eur J Med Chem 45:5827–5832

    Article  CAS  PubMed  Google Scholar 

  • Herencia F, Ferrandiz ML, Ubeda A, Dominguez JN, Charris JE, Lobo GM, Alcaraz MJ (1998) Synthesis and anti-inflammatory activity of chalcone derivatives. Bioorg Med Chem Lett 8:1169–1174

    Article  CAS  PubMed  Google Scholar 

  • Hotta N, Akanuma Y, Kawamori R, Matsuoka K, Oka Y, Shichiri M, Toyata T, Nakashima M, Yoshimura I, Sakamoto N, Shigeta Y (2006) Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy: the 3-year, multicenter, comparatives aldose reductase inhibitor-diabetes complications trial. Diabetes Care 29:1538–1544

    Article  CAS  PubMed  Google Scholar 

  • Jin X, Zeheng CJ, Song MX, Wu Y, Sun LP, Li YJ, Yu LJ, Piao HR (2012) Synthesis and antimicrobial evaluation of l-phenylalanine-derived C5-substituted rhodanine and chalcone derivatives containing thibarbituric acid or 2-thioxo-4-thiazolidinone. Eur J Med Chem 56:203–209

    Article  CAS  PubMed  Google Scholar 

  • Kashfi K, Enna SJ, Michael W (2009) Anti-inflammatory agents as cancer therapeutics. Advances in pharmacology. Academic Press, New York, pp 31–89

    Google Scholar 

  • Katsori AM, Hadjipavlou-Litina D (2009) Chalcone in cancer: understanding their rolein terms of QSAR. Curr Med Chem 16:1062–1081

    Article  CAS  PubMed  Google Scholar 

  • Kimura Y (2005) New anticancer agents: in vitro and in vivo evaluation of the antitumor and antimetastatic actions of various compounds isolated from medicinal plants. In Vivo 19:37–60

    CAS  PubMed  Google Scholar 

  • Kontogiorgis C, Mantzanidou M, Hadjipavlou-Litina D (2008) Chalcones and their potential role in inflammation. Mini Rev Med Chem 8:1224–1242

    Article  CAS  PubMed  Google Scholar 

  • Lawrence NJ, McGown AT (2005) The chemistry and biology of antimitotic chalcones and related enone systems. Curr Pharm Des 11:1679–1693

    Article  CAS  PubMed  Google Scholar 

  • Lin YM, Zhou Y, Flavin MT, Zhou LM, Nie W, Chen FC (2002) Chalcones and flavonoids as anti-tuberculosis agents. Bioorg Med Chem 10:2795–2802

    Article  CAS  PubMed  Google Scholar 

  • Liu M, Wilairat P, Croft SL, Tan AL, Go ML (2003) Structure-activity relationship of antileishmanial and antimalarial chalcones. Bioorg Med Chem 11:2729–2738

    Article  CAS  PubMed  Google Scholar 

  • Liu HL, Jiang WB, Xie MX (2010) Flavonoids: recent advances as anticancer drugs. Recent Pat Anticancer Drug Discov 5:152–164

    Article  PubMed  Google Scholar 

  • Maestro (2013) version 9.3; Schrodinger, LLC, New York, NY

  • Min G, Lee S, Kim H, Han Y, Lee R, Jeong DW, Han DC, Kwon B (2013) Rhodanine-based PRL-3 inhibitors blocked the migration and invasion of metastatic cancer cells. Bioorg Med Chem Lett 23:3769–3774

    Article  CAS  PubMed  Google Scholar 

  • Momose Y, Meguro K, Ikeda H, Hatanaka C, Oi S, Sohda T (1991) Studies on antidiabetic agents. X. Synthesis and biological activities of pioglitazone and related compounds. Chem Pharm Bull 39:1440–1445

    Article  CAS  PubMed  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survrvial. Application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  PubMed  Google Scholar 

  • Nowakowska Z (2007) Areview of anti-infective and anti-inflammatory chalcones. Eur J Med Chem 42:125–137

    Article  CAS  PubMed  Google Scholar 

  • Ohishi Y, Mukai T, Nagahara M, Yajima M, Kajikawa N, Miyahara K, Takano T (1990) Preparation of 5-alkylmethylidene-3-carboxymethylrhodanine derivatives and their aldose reductase inhibitory activity. Chem Pharm Bull 38:1911–1919

    Article  CAS  PubMed  Google Scholar 

  • Opletalova V (2000) Chalcones and there heterocyclic analogs as potential therapeutic agents in bacterial diseases. Ceska Slov Farm 49:278–284

    CAS  PubMed  Google Scholar 

  • Opletalova V, Sedivy D (1999) Chalcones and there heterocyclic analogs as potential antifungal chemotherapeutic agents. Ceska Slov Farm 48:252–255

    CAS  PubMed  Google Scholar 

  • Opletalova V, Jahodar L, Jun D, Opletal L (2003) Chalcones (1,3-diarylpropen-1-ones) and their analogs as potential therapeutic agents incardiovascular system diseases. Ceska Slov Farm 52:12–19

    CAS  PubMed  Google Scholar 

  • Padhye S, Ahmad A, Oswal N, Sarkar FH (2009) Emerging role of garcinol, the antioxidant chalcone from garcinia indica choisy and its synthetic analogs. J Hematol Oncol 2:38

    Article  PubMed Central  PubMed  Google Scholar 

  • Phase (2013) version 3.4, Schrödinger, LLC, New York, NY

  • Ravi S, Chiruvella KK, Rajesh K, Prabhu V, Raghavan SC (2010) 5-Isopropylidene-3-ethyl rhodanine induce growth inhibition followed by apoptosis in leukemia cells. Eur J Med Chem 45:2748–2752

    Article  CAS  PubMed  Google Scholar 

  • Rostom SAF (2006) Synthesis and in vitro antitumor evaluation of some Indeno [1,2-c]-pyrazol(in)es substituted with sulfonamide, sulfonylurea (thiourea) pharmacophores, and some derived thiazole ring systems. Bioorg Med Chem 14:6475–6485

    Article  CAS  PubMed  Google Scholar 

  • Sortino M, Delgado P, Juarez S, Quiroga J, Abonia R, Insuasty B, Nogueras M, Rodero L, Garibotto FM, Enriz RD, Zacchino SA (2007) Synthesis and antifungal activity of (Z)-5-arylidenerhodanines. Bioorg Med Chem 15:484–494

    Article  CAS  PubMed  Google Scholar 

  • Volynets GP, Bdzhola VC, Golub AG, Synyugin AR, Chekanov MA, Kukharenko OP, Yarmoluk SM (2013) Rational design of apoptosis signal-regulating kinase 1 inhibitors: discovering novel structural scaffold. Eur J Med Chem 61:104–115

    Article  CAS  PubMed  Google Scholar 

  • WHO/Cancer-World Health Organisation (2013) http://www.who.int/topics/cancer/en/. Accessed 1 Nov 2013

  • Yadav VR, Prasad S, Sung B, Aggarwal BB (2011) The role of chalcones in suppression of NF-KB-mediated inflammation and cancer. Int Immunopharmacol 11:295–309

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans W, Speck W (1987) Salmonella mutagenicity tests: III. Results from the testing of 225 chemicals. Environ Mutagen 9:1–110

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Authors are grateful to Dr. A. D. Taranalli, Principal and Dean Faculty of pharmacy, for providing necessary facilities for the research. Abounded thanks are due to Dr. Raghu for providing the Schrodinger software and also for the encouragement and motivation to complete the computational studies. Authors are also grateful to NMR Research center, IISC, Bangalore, India, for providing the spectral data.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, KLE University’s College of Pharmacy, Nehrunagar, Belgaum, 590 010, Karnataka, India

    Shankar G. Alegaon & Kallanagouda R. Alagawadi

  2. Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College, Chennai, 600 003, India

    D. Vinod

  3. Department of Pharmacology and Toxicology, KLE University’s College of Pharmacy, Nehrunagar, Belgaum, 590 010, Karnataka, India

    Banappa Unger & N. A. Khatib

Authors
  1. Shankar G. Alegaon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kallanagouda R. Alagawadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Vinod
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Banappa Unger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. A. Khatib
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shankar G. Alegaon.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 881 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alegaon, S.G., Alagawadi, K.R., Vinod, D. et al. Synthesis, pharmacophore modeling, and cytotoxic activity of 2-thioxothiazolidin-4-one derivatives. Med Chem Res 23, 5160–5173 (2014). https://doi.org/10.1007/s00044-014-1087-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-014-1087-9

Keywords

Search

Navigation