Skip to main content

Advertisement

SpringerLink
Log in

Synthesis and in vitro antiproliferative activity against human cancer cell lines of novel 5-(4-methyl-benzylidene)-thiazolidine-2,4-diones

  • PHASE I STUDIES
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

A series of novel 5-(4-methyl-benzylidene)-thiazolidine-2,4-dione derivatives 6 (a–d) and 7 (a–g) were synthesized with different substituted aromatic sulfonyl chlorides (R–SO2–Cl) and alkyl halides (R–X) and were characterized by 1H NMR, LC/MS, FTIR and elemental analyses. All the compounds synthesised were evaluated for their cell antiproliferation activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The antiproliferative effects of the synthesised compounds were tested against viable human skin fibroblast cell line and carcinoma cell lines namely HeLa cells, HT-29 cells, MCF-7 cells, HepG-2 cells by adopting positive and negative control. The importance of the nitro group on thiazolidinone moiety was confirmed and it was concluded that the fourth position of the substituted aryl ring plays a dominant role and was responsible for the antiproliferative activity. Among the synthesized compounds only 6a, 7e and 7g have potent antiproliferative activity on all the carcinoma cell lines tested.

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

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Sawyers C (2004) Targeted cancer therapy. Nature 432:294–297

    Article  PubMed  CAS  Google Scholar 

  2. Li Q, Xu W (2005) Novel anticancer targets and drug discovery in post genomic age. Curr Med Chem Anticancer Agents 5:53–63

    Article  PubMed  CAS  Google Scholar 

  3. Guo T, Hobbs DW (2003) Privileged structure-based combinatorial libraries. targeting G protein-coupled receptors. Assay Drug Dev Technol 1:579–592

    Article  PubMed  CAS  Google Scholar 

  4. Horton DA, Bourne GT, Smythe ML (1999) Exploring privileged structures: the combinatorial synthesis of peptides. Mol Diversity 5:289–304

    Article  Google Scholar 

  5. Franzen RG (2000) Recent advances in the preparation of heterocycles on solid support: A review of the literature. J Comb Chem 2:195

    Article  PubMed  CAS  Google Scholar 

  6. Lakhan R, Rai BJ (1987) Synthesis and antibacterial activity of 2-[[omega.-(dialkylamino)alkyl]thio]-3-aryl(oralkyl)-6,8-disubstituted-4(3H)-quinazolinones. J Chem Eng Data 32:384–386

    Article  CAS  Google Scholar 

  7. Hour MJ, Huang LJ, Kuo SC, Xia Y, Bastow K, Nakanishi Y, Hamel E, Lee KH (2000) 6-Alkylamino- and 2,3-dihydro-3′-methoxy-2-phenyl-4-quinazolinones and related compounds: their synthesis, cytotoxicity, and inhibition of tubulin polymerization. J Med Chem 43:4479–87

    Article  PubMed  CAS  Google Scholar 

  8. Hamel E, Lin CM, Plowman J, Wang HK, Hsiung Lee K, Paull KD (1996) Antitumor 2,3-dihydro-2-(aryl)-4(1H)-quinazolinone derivatives: interactions with tubulin. Biochem Pharmacol 51:53–59

    Article  PubMed  CAS  Google Scholar 

  9. Corbett JW, Ko SS, Rodgers JD, Gearhart LA, Magnus NA, Bacheler LT, Diamond S, Jeffrey S, Klabe RM, Cordova BC, Garber S, Logue K, Trainor GL, Anderson PS, Erickson-Viitanen SK (2000) Inhibition of clinically relevant mutant variants of HIV-1 by quinazolinone non-nucleoside reverse transcriptase inhibitors. J Med Chem 43:2019–2030

    Article  PubMed  CAS  Google Scholar 

  10. Archana, Srivastava VK, Kumar A (2003) Synthesis of newer indolyl thiadiazoles and their thiazolidinones and formazans as potential anticonvulsant agents. Ind J Pharm Sci 63:358–362

    Google Scholar 

  11. Gundurao K, Vinayak H, Imtiyaz AK, Pramod G (2006) Synthesis and evaluation of antitubercular activity of imidazo[2,1-b][1,3,4]thiadiazole derivatives. Bioorg Med Chem 14:3069–3080

    Article  CAS  Google Scholar 

  12. Samir B, Wesam K, Ahmed AF (2007) Synthesis and antimicrobial evaluation of some new thiazole, thiazolidinone and thiazoline derivatives starting from 1-chloro-3,4-dihydronaphthalene-2-carboxaldehyde. Eur J Med Chem 42:948–954

    Article  CAS  Google Scholar 

  13. Bartroli J, Turmo E, Alguero M, Boncompte E, Vericat ML, Conte L, Ramis J, Merlos M, García-Rafanell J, Forn J (1998) New azole antifungals. 3. Synthesis and antifungal activity of 3-substituted-4(3H)-quinazolinones. J Med Chem 41:1869–1882

    Article  PubMed  CAS  Google Scholar 

  14. Goel B, Ram T, Tyagi R, Bansal E, Kumar A, Mukherjee D, Sinha JN (1999) 2-Substituted-3-(4-bromo-2-carboxyphenyl)-5-methyl-4-thiazolidinones as potential anti-inflammatory agents. Eur J Med Chem 34:265–269

    Article  CAS  Google Scholar 

  15. Smith WL, Dewitt DL (1996) Prostaglandin endoperoxide H synthases-1 and -2. Adv Immunol 62:167–215

    Article  PubMed  CAS  Google Scholar 

  16. Herschman HR (1996) Prostaglandin synthases 2. Biochim Biophys Acta 1299:125–140

    PubMed  Google Scholar 

  17. Picot D, Loll PJ, Garavito RM (1994) The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1. Nature 367:243–249

    Article  PubMed  CAS  Google Scholar 

  18. Meyer BN, Ferrigni NR, Putnam JE, Jacobsen LB, Nichols DE, McLaughlin L (1982) Brine shrimp: a convenient general bioassay for active plant constituents. Planta Medica 45:31–34

    Article  CAS  Google Scholar 

  19. Barreca ML, 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. Bioorg Med Chem Lett 11:1793–1796

    Article  PubMed  CAS  Google Scholar 

  20. Andres CJ, Bronson JJ, D’Andrea SV, Deshpande MS, Falk PJ, Young KA, Harte WE, Ho HT, Misco PF, Robertson JG, Stock D, Sun Y, Walsh AW (2000) 4-Thiazolidinones: novel inhibitors of the bacterial enzyme murB. Bioorg Med Chem Lett 10:715–717

    Article  PubMed  CAS  Google Scholar 

  21. Medina JC, Shan B, Beckmann H, Farrell RP, Clark DL, Learned RM, Roche D, Li A, Baichwal V, Case C, Baeuerle PA, Rosen T, Jaen JC (1998) Novel antineoplastic agents with efficacy against multidrug resistant tumor cells. Bioorg Med Chem Lett 8:2653–2656

    Article  PubMed  CAS  Google Scholar 

  22. Shan B, Medina JC, Santha E, Frankmoelle WP, Chou TC, Learned RM, Narbut MR, Stott D, Wu P, Jaen JC, Rosen T, Timmermans PBMWM, Beckmann H (1999) Selective, covalent modification of b-tubulin residue Cys-239 by T138067, an antitumor agent with in vivo efficacy against multidrug-resistant tumors. Proc. Nat Acad Sci USA 96:5686–5691

    Article  PubMed  CAS  Google Scholar 

  23. Chen H, Fan Y-H, 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 14:5401–5405

    Article  PubMed  CAS  Google Scholar 

  24. Anil Kumar C, Nanjunda Swamy S, Gaonkar SL, Basappa, Bharathi PS, Rangappa KS (2007) N-Substituted-2-butyl-5-chloro-3H-imidazole-4-carbalderhyde derivatives as anti-tumor agents against ehrilch ascites tumor cells in vivo. Med Chem 3:269–276

    Article  PubMed  Google Scholar 

  25. Anil Kumar C, Jayarama S, Basappa, Bharathi PS, Rangappa KS (2007) Pro-apoptotic activity of imidazole derivatives mediated by up-regulation of Bax and activation of CAD in Ehrlich Ascites Tumor cells. Invest New Drugs 25:343–350

    Article  PubMed  CAS  Google Scholar 

  26. Ananda Kumar CS, Nanjunda Swamy S, Thimmegowda NR, Benaka Prasad SB, Yip GW, Rangappa KS (2007) Synthesis and evaluation of 1-benzhydryl-sulfonyl-piperazine derivatives as inhibitors of MDA-MB-231 human breast cancer cell proliferation. Med Chem Res 16(4):179–187

    Article  CAS  Google Scholar 

  27. Priya BS, Anil Kumar C, Nanjunda Swamy S, Basappa, Naveen S, Rangappa KS (2007) 2-(2-(2-ethoxybenzoylamino)-4-chlorophenoxy)-N-(2-ethoxybenzoyl) benzamine inhibits EAT cell induced angiogenesis by down regulation of VEGF secretion. Bioorg Med Chem Lett 17:2775

    Article  PubMed  CAS  Google Scholar 

  28. Scudiero DA, Shoemaker RH, Paull KD, Monks A, Tierney S, Nofziger TH, Currens MJ, Seniff D, Boyd MR (1988) Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res 48:4827–4833

    PubMed  CAS  Google Scholar 

  29. Laura G, Marinella R, Erik DC (2002) Synthesis and antiviral/antiproliferative activity of some N-sulphonylbenzimidazoles. Bioorg Med Chem Lett 12:2707–2710

    Article  Google Scholar 

  30. Wilson WR, Denny WA, Twigden SJ, Baguley BC, Probert JC (1984) Selective toxicity of nitracrine to hypoxic mammalian cells. Br J Cancer 49:215–223

    PubMed  CAS  Google Scholar 

  31. Pawlak K, Matuszkiewicz A, Pawlak JW, Konopa J (1983) The mode of action of cytotoxic and antitumor 1-nitroacridines. I. The 1-nitroacridines do not exert their cytotoxic effects by physicochemical binding with DNA. Chem Biol Interact 43:131–149

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to UGC, Govt. of India for financial support to K.S.R. under the projects vide No. F. 31-143/2005(SR) and UGC-SAP (Phase I) vide No. F. 540/10/2004-05 (SAP I). The CHNS data from the instrument granted by DST-FIST programme order No. SR/FST/CSI-051/2002 is greatly acknowledged. Authors CS and SBBP wish to thank Prof. Sanjay Swarup, Department of Biological Sciences, National University of Singapore, Singapore for the use of laboratory facilities to carry out antiproliferative studies.

Author information

Authors and Affiliations

  1. Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, 570006, India

    S. Chandrappa, S. B. Benaka Prasad, K. Vinaya, C. S. Ananda Kumar, N. R. Thimmegowda & K. S. Rangappa

Authors
  1. S. Chandrappa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. B. Benaka Prasad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Vinaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. S. Ananda Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. R. Thimmegowda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. S. Rangappa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. S. Rangappa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chandrappa, S., Benaka Prasad, S.B., Vinaya, K. et al. Synthesis and in vitro antiproliferative activity against human cancer cell lines of novel 5-(4-methyl-benzylidene)-thiazolidine-2,4-diones. Invest New Drugs 26, 437–444 (2008). https://doi.org/10.1007/s10637-008-9130-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-008-9130-7

Keywords

Search

Navigation