Skip to main content

Advertisement

SpringerLink
Log in

Synthesis and antiproliferative activity evaluation of new thiazole–benzimidazole derivatives using real-time cell analysis (RTCA DP)

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

Abstract

A series of new 2-[(5-substituted-1H-benzimidazol-2-yl)thio]-N-[4-[2-phenylthiazol-4-yl]phenyl]acetamide derivatives (4a–p) were synthesized according to the reported literature, and anticancer activity of the compounds was evaluated. Cytotoxic activity was confirmed by real-time cytotoxicity analysis system determining half maximal inhibitory concentrations (IC50) of the title compounds based on the dose–response curves derived by xCELLigence measurements against NIH/3T3, A549 and Caco2 cell lines for 24, 48 and 72 h exposure. Compound 4c was found to be as the most efficient molecule that exhibited selective antiproliferative activity against both of the cancer cells.

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

Similar content being viewed by others

References

  • Abraham AT, Lin JJ, Newton DL, Rybak S, Hecht SM (2003) RNA cleavage and inhibition of protein synthesis by bleomycin. Chem Biol 10:45–52

    Article  CAS  PubMed  Google Scholar 

  • Al-Omary FA, Hassan GS, El-Messery SM, El-Subbagh HI (2012) Substituted thiazoles V. synthesis and antitumor activity of novel thiazolo[2,3-b]quinazoline and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine analogues. Eur J Med Chem 47:65–72

    Article  CAS  PubMed  Google Scholar 

  • Alpan AS, Zencir S, Zupko I, Coban G, Rethy B, Gunes HS, Topcu Z (2009) Biological activity of bis-benzimidazole derivatives on DNA topoisomerase I and HeLa, MCF7 and A431 cells. J Enzyme Inhib Med Chem 24:844–849

    Article  CAS  PubMed  Google Scholar 

  • Bailly C, Kenani A, Waring MJ (1997) Altered cleavage of DNA sequences by bleomycin and its deglycosylated derivative in the presence of actinomycin. Nucleic Acids Res 25:1516–1522

    Article  CAS  PubMed  Google Scholar 

  • Bird C, Kirstein S (2009) Real-time, label-free monitoring of cellular invasion and migration with the xCELLigence system. Nat Methods 6:v–vi

    CAS  Google Scholar 

  • Bryant HE, Helleday T (2004) Poly(ADP-ribose) polymerase inhibitors as potential chemotherapeutic agents. Biochem Soc Trans 32:959–961

    Article  CAS  PubMed  Google Scholar 

  • Cai X, Gray PJ Jr, Von Hoff DD (2009) DNA minor groove binders: back in the Groove. Cancer Treat Rev 35:437–450

    Article  CAS  PubMed  Google Scholar 

  • Calabrese CR, Almassy R, Barton S, Batey MA, Calvert AH, Canan-Koch S, Durkacz BW, Hostomsky Z, Kumpf RA, Kyle S, Li J, Maegley K, Newell DR, Notarianni E, Stratford IJ, Skalitzky D, Thomas HD, Wang L, Webber SE, Williams KJ, Curtin NJ (2004) Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J Natl Cancer Inst 96:56–67

    Article  CAS  PubMed  Google Scholar 

  • Chabner BA, Roberts TG (2005) Timeline: chemotherapy and the war on cancer. Nat Rev Cancer 5:65–72

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Pankiewicz K (2007) Recent development of IMP dehydrogenase inhibitors for the treatment of cancer. Curr Opin Drug Discov Devel 10:403–412

    CAS  PubMed  Google Scholar 

  • Colvin OM (1999) An overview of cyclophosphamide development and clinical applications. Curr Pharm Des 5:555–560

    CAS  PubMed  Google Scholar 

  • Da Rocha AB, Lopes RM, Schwartsmann G (2001) Natural products in anticancer therapy. Curr Opin Pharmacol 1:364–369

    Article  PubMed  Google Scholar 

  • Delgado JN, Remers WA (1998) Textbook of organic medicinal and pharmaceutical chemistry. Lippincott JB Co, Philadelphia

    Google Scholar 

  • El-Messery SM, Hassan GS, Al-Omary FA, El-Subbagh HI (2012) Substituted thiazoles VI. Synthesis and antitumor activity of new 2-acetamido- and 2 or 3-propanamido-thiazole analogs. Eur J Med Chem 54:615–625

    Article  CAS  PubMed  Google Scholar 

  • El-Subbagh HI, Al-Obaid AM (1996) 2,4-Disubstituted thiazoles II. A novel class of antitumor agents, synthesis and biological evaluation. Eur J Med Chem 39:1017–1021

    Article  Google Scholar 

  • El-Subbagh HI, El-Naggar WA, Badria FA (1994) Synthesis and biological testing of 2,4-disubstituted thiazole derivatives as potential antitumor antibiotics. Med Chem Res 3:503–516

    CAS  Google Scholar 

  • El-Subbagh HI, Abadi AH, Lehmann J (1999) 2,4-Disubstituted thiazoles, Part III. Synthesis and antitumor activity of ethyl 2-substituted-aminothiazole-4-carboxylate analogs. Arch Pharm (Weinheim) 332:137–142

    Article  CAS  Google Scholar 

  • El-Subbagh HI, Al-Khawad IE, El-Bendary ER, Al-Obaid AM (2001) Substituted thiazoles IV: synthesis and antitumor activity of new substituted ımidazo [2, 1-b] thiazole analogs. Saudi Pharm 9:14

    CAS  Google Scholar 

  • Foy WO, Lemka TL, Williams DA (2008) Principles of medicinal chemistry. Williams and Wilkins Media PA, Philadelphia

    Google Scholar 

  • Hammond LA, Davidson K, Lawrence R, Camden JB, Von Hoff DD, Weitman S, Izbicka E (2001) Exploring the mechanisms of action of FB642 at the cellular level. J Cancer Res Clin Oncol 127:301–313

    Article  CAS  PubMed  Google Scholar 

  • Hao D, Rizzo JD, Stringer S, Moore RV, Marty J, Dexter DL, Mangold GL, Camden JB, Von Hoff DD, Weitman SD (2002) Invest New Drugs 20:261–270

    Article  CAS  PubMed  Google Scholar 

  • Hranjec M, Kralj M, Piantanida I, Sedic M, Suman L, Pavelic K, Karminski Zamola G (2007) Novel cyano- and amidino-substituted derivatives of styryl-2-benzimidazoles and benzimidazo[1,2-a]quinolines. Synthesis, photochemical synthesis, DNA binding, and antitumor evaluation, Part 3. J Med Chem 50:5696–5711

    Article  CAS  PubMed  Google Scholar 

  • Huang S, Hsei I, Chen C (2006) Synthesis and anticancer evaluation of bis(benzimidazoles), bis(benzoxazoles), and benzothiazoles. Bioorg Med Chem 14:6106–6119

    Article  CAS  PubMed  Google Scholar 

  • Hurley LH (2002) DNA and its associated processes as targets for cancer therapy. Nat Rev Cancer 2:188–200

    Article  CAS  PubMed  Google Scholar 

  • Kim JS, Gatto B, Yu C, Liu A, Liu LF, LaVioe E (1996) Substituted 2,5′-Bi-1H-benzimidazoles: topoisomerase I inhibition and cytotoxicity. J Med Chem 39:992–998

    Article  CAS  PubMed  Google Scholar 

  • Kumar Y, Green R, Barysko KZ, Wise DS, Wotring LL, Townsend LB (1993) Synthesis of 2,4-disubstituted thiazoles and selenazoles as potential antitumor and antifilarial agents: 1. Methyl 4-(isothiocyanatomethyl)thiazole-2-carbamates, -selenazole-2-carbamates, and related derivatives. J Med Chem 36:3843–3848

    Article  CAS  PubMed  Google Scholar 

  • Kumar D, Jacob MR, Reynolds MB, Kerwin SM (2002) Synthesis and evaluation of anticancer benzoxazoles and benzimidazoles related to UK-1. Bioorg Med Chem 10:3997–4004

    Article  CAS  PubMed  Google Scholar 

  • Le Sann C, Baron A, Mann J, van den Berg H, Gunaratnam M, Neidle S (2006) New mustard-linked 2-aryl-bis-benzimidazoles with anti-proliferative activity. Org Biomol Chem 4:1305–1312

    Article  PubMed  Google Scholar 

  • Moe B, Gabos SF, Li X (2013) Real-time cell-microelectronic sensing of nanoparticle-induced cytotoxic effects. Anal Chim Acta 789:83–90

    Article  CAS  PubMed  Google Scholar 

  • Neidle S, Mann J, Rayner EL, Baron A, Opoku-Boahen Y, Simpson IJ, Smith NJ, Fox KR, Hartley JA, Kelland LR (1999) Symmetric bis-benzimidazoles: new sequence-selective DNA-binding molecules. Chem Commun 10:929–930

    Article  Google Scholar 

  • Nelson SM, Ferguson LR, Denny WA (2007) Non-covalent ligand/DNA interactions: minor groove binding agents. Mutat Res 623:24–40

    Article  CAS  PubMed  Google Scholar 

  • Piskin AK, Ates-Alagoz Z, Atac FB, Musdal Y, Buyukbingol E (2009) DNA binding and antiproliferative effects of some benzimidazole retinoids. Turk J Biochem 34:39–43

    CAS  Google Scholar 

  • Plouvier B, Houssin R, Helbecque N, Colson P, Houssier C, Henichart JP, Bailly C (1995) Influence of the methyl substituents of a thiazole-containing lexitropsin on the mode of binding to DNA. Anticancer Drug Des 10:155–166

    CAS  PubMed  Google Scholar 

  • Popsavin M, Spaic S, Svircev M, Kojic V, Bogdanovic G, Popsavin V (2007) Synthesis and antitumour activity of new tiazofurin analogues bearing a 2,3-anhydro functionality in the furanose ring. Bioorg Med Chem Lett 1:4123–4127

    Article  Google Scholar 

  • Prudhomme M (2006) Novel checkpoint 1 inhibitors. Recent Pat Anticancer Drug Discov 1:55–68

    Article  CAS  PubMed  Google Scholar 

  • Rowinsky EK, Onetto N, Canetta RM, Arbuck SG (1992) Taxol: the first of the taxanes, an important new class of antitumor agents. Semin Oncol 19:646–692

    CAS  PubMed  Google Scholar 

  • Schnur RC, Gallaschun RJ, Singleton DH, Grissom M, Sloan DE, Goodwin P, McNiff PA, Fliri AF, Mangano FM, Olson TH (1991) Quantitative structure-activity relationships of antitumor guanidinothiazolecarboxamides with survival enhancement for therapy in the 3LL Lewis lung carcinoma model. J Med Chem 34:1975–1982

    Article  CAS  PubMed  Google Scholar 

  • Silvermann RB (1992) The organic chemistry of drug design and drug action. Academic Press, San Diego

    Google Scholar 

  • Solly K, Wang X, Xu X, Strulovici B, Zheng W (2004) Application of real-time cell electronic sensing (RT-CES) technology to cell-based assays. Drug Dev Technol 2:363–372

    Article  CAS  Google Scholar 

  • Tong Y, Bouska JJ, Ellis PA, Johnson EF, Leverson J, Liu X, Marcotte PA, Olson AM, Osterling DJ, Przytulinska M, Rodriguez LE, Shi Y, Soni N, Stavropoulos J, Thomas S, Donawho CK, Frost DJ, Luo Y, Giranda VL, Penning TD (2009) Synthesis and evaluation of a new generation of orally efficacious benzimidazole-based poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors as anticancer agents. J Med Chem 52:6803–6813

    Article  CAS  PubMed  Google Scholar 

  • Urcan E, Haertel U, Styllou M, Hickel R, Scherthan H, Reichla FX (2010) Real-time xCELLigence impedance analysis of the cytotoxicity of dental composite components on human gingival fibroblasts. Dental Mater 26:51–58

    Article  CAS  Google Scholar 

  • Wolter FE, Molinari L, Socher ER, Schneider K, Nicholson G, Beil W, Seitz O, Süssmuth RD (2009) Synthesis and evaluation of a netropsin-proximicin-hybrid library for DNA binding and cytotoxicity. Bioorg Med Chem Lett 15:3811–3815

    Article  Google Scholar 

  • Workman P (2005) Genomics and the second golden era of cancer drug development. Mol BioSyst 1:17–26

    Article  CAS  PubMed  Google Scholar 

  • Workman P, Colins I (2008) Modern cancer drug discovery: Integrating targets, technologies and treatments. In: Neidle S (ed) Cancer drug design and discovery. Academic Press, Cambridge, pp 3–38

    Chapter  Google Scholar 

  • Yamamoto K, Kawanishi S (1992) Enhancement and alteration of bleomycin-catalyzed site-specific DNA cleavage by distamycin A and some minor groove binders. Biochem Biophys Res Commun 183:292–299

    Article  CAS  PubMed  Google Scholar 

  • Yurttas L, Ozkay Y, Akalın-Ciftci G, Ulusoylar-Yıldırım S (2014) Synthesis and anticancer activity evaluation of N-[4-(2-methylthiazol-4-yl)phenyl]acetamide derivatives containing (benz)azole moiety. J Enzyme Inhib Med Chem 29:175–184

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470, Eskisehir, Turkey

    Yusuf Özkay & Leyla Yurttaş

  2. Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470, Eskisehir, Turkey

    Miriş Dikmen & Selin Engür

Authors
  1. Yusuf Özkay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leyla Yurttaş
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miriş Dikmen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Selin Engür
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leyla Yurttaş.

Ethics declarations

Conflict of interests

The authors report no conflict of interest.

Ethical statement

For this type of study formal consent is not required. Informed consent was obtained from all individual participants included in the study.

Additional information

All cell lines were purchased from ATCC with account number 20033704 on behalf of Miriş Dikmen.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1208 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Özkay, Y., Yurttaş, L., Dikmen, M. et al. Synthesis and antiproliferative activity evaluation of new thiazole–benzimidazole derivatives using real-time cell analysis (RTCA DP). Med Chem Res 25, 482–493 (2016). https://doi.org/10.1007/s00044-016-1507-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-016-1507-0

Keywords

Search

Navigation