Monatshefte für Chemie - Chemical Monthly

, Volume 149, Issue 11, pp 2093–2102 | Cite as

Synthesis and biological evaluation of 2-(3-aminophenyl)-benzothiazoles as antiproliferative and apoptosis-inducing agents

  • Juan Zhang
  • Zhi-Qiang Cheng
  • Jia-Li Song
  • Hong-Rui Tao
  • Kongkai Zhu
  • Luis Alexandre Muehlmann
  • Cheng-Shi JiangEmail author
  • Hua ZhangEmail author
Original Paper


A series of new 2-(3-aminophenyl)-benzothiazole derivatives were synthesized and evaluated for their in vitro antiproliferative activity against various human cancer cell lines including A549, HeLa, HepG2, MCF-7, MV4-11, and DB. Among the tested compounds, N-[3-(benzo[d]thiazol-2-yl)phenyl]nicotinamide displayed significantly improved antiproliferative activity toward A549 and MV4-11 cells with IC50 values of 5.42 ± 1.33 and 7.51 ± 0.98 μM, respectively, much stronger than the hit 3-(benzo[d]thiazol-2-yl)-N-(4-bromobenzyl)aniline. Furthermore, flow cytometric analysis indicated that N-[3-(benzo[d]thiazol-2-yl)phenyl]nicotinamide induced A549 cell apoptosis with cell cycle arrest at G1 phase in a concentration-dependent manner.

Graphical abstract


Heterocycles Cytotoxicity Antitumor agents Cell cycle arrest Structure–activity relationships 



This research work was financially supported by the National Natural Science Foundation of China (No. 21672082), Shandong Key Development Project (No. 2016GSF201209), the Young Taishan Scholars Program (No. tsqn20161037), Natural Science Foundation of Shandong Province (Nos. ZR2017BH038, JQ201721), Shandong Talents Team Cultivation Plan of University Preponderant Discipline (No. 10027), and the Brazilian Government Agencies FAP/DF and CNPq.

Supplementary material

706_2018_2274_MOESM1_ESM.doc (2.6 mb)
Supplementary material 1 (DOC 2686 kb)


  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) CA Cancer J Clin 61:69CrossRefGoogle Scholar
  2. 2.
    GBD 2015 Disease and Injury Incidence and Prevalence Collaborators (2016) Lancet 388:1545CrossRefGoogle Scholar
  3. 3.
    World Cancer Report (2014) World Health Organization. Accessed 3 Mar 2018Google Scholar
  4. 4.
    Zhang J, Yang F, Qiao Z, Zhu M, Zhou H (2016) Bioorg Med Chem Lett 26:5797CrossRefGoogle Scholar
  5. 5.
    Tantawy MA, Nafie MS, Elmegeed GA, Ali IAI (2017) Bioorg Chem 73:128CrossRefGoogle Scholar
  6. 6.
    Rai A, Singh AK, Raj V, Saha S (2018) Mini Rev Med Chem 18:42PubMedGoogle Scholar
  7. 7.
    Akhtar MJ, Yar MS, Khan AA, Ali Z, Haider MR (2017) Mini Rev Med Chem 17:1602CrossRefGoogle Scholar
  8. 8.
    Rouf A, Tanyeli C (2015) Eur J Med Chem 97:911CrossRefGoogle Scholar
  9. 9.
    Mei WW, Ji SS, Xiao W, Wang XD, Jiang CS, Ma WQ, Zhang HY, Gong JX, Guo YW (2017) Monatsh Chem 148:1807CrossRefGoogle Scholar
  10. 10.
    Thakkar SS, Thakor P, Ray A, Doshi H, Thakkar VR (2017) Bioorg Med Chem 25:5396CrossRefGoogle Scholar
  11. 11.
    Bhat M, Belagali SL (2018) Future Med Chem 10:71CrossRefGoogle Scholar
  12. 12.
    Cindrić M, Jambon S, Harej A, Depauw S, David-Cordonnier MH, Kraljević Pavelić S, Karminski-Zamola G, Hranjec M (2017) Eur J Med Chem 136:468CrossRefGoogle Scholar
  13. 13.
    Al-Harthy T, Zoghaib WM, Stoll R (2018) Monatsh Chem 149:645CrossRefGoogle Scholar
  14. 14.
    Kamal A, Syed MA, Mohammed SM (2015) Expert Opin Ther Pat 25:335CrossRefGoogle Scholar
  15. 15.
    Capuyo R, Calabrò ML, Micale N, Schimmer AD, Ali M, Zappalà M, Grasso S (2015) Med Chem Res 21:2644CrossRefGoogle Scholar
  16. 16.
    Hutchinson I, Chua MS, Browne HL, Trapani V, Bradshaw TD, Westwell AD, Stevens MF (2001) J Med Chem 44:1446CrossRefGoogle Scholar
  17. 17.
    Zhang Y, Chakraborty M, Cerda-Smith CG, Bratton RN, Maurer NE, Senser EM, Novak M (2013) J Org Chem 78:6992CrossRefGoogle Scholar
  18. 18.
    Chhabra M, Sinha S, Banerjee S, Paira P (2016) Bioorg Med Chem Lett 26:213CrossRefGoogle Scholar
  19. 19.
    Ehlert J, Herz T, Krauss R, Kubbutat M, Lang M, Saeb W, Schaechtele C, Tasler S, Totzke F, Zirrgiebel U (2007) 2-Arylbenzothiazole analogs as kinase inhibitors and their preparation, pharmaceutical compositions and use in the treatment of kinase-mediated diseases. US patent 20070021446 ((2007) Chem Abstr 146:184430)Google Scholar
  20. 20.
    Ehlert J, Herz T, Krauss R, Kubbutat M, Martin L, Saeb W, Schaechtele C, Tasler S, Totzke F, Zirrgiebel U (2007) Preparation of 2-heteroarylaminophenylbenzothiazoles as anticancer drugs. European patent EP 1746096 A1 ((2007) Chem Abstr 146:184428)Google Scholar
  21. 21.
    Asahara H (2017) Proc Eng 174:1046CrossRefGoogle Scholar
  22. 22.
    Mosmann T (1983) J Immunol Methods 65:55CrossRefGoogle Scholar
  23. 23.
    Wang J, Sánchez-Roselló M, Aceña JL, del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H (2014) Chem Rev 114:2432CrossRefGoogle Scholar
  24. 24.
    Shankaraiaha N, Nekkantia S, Brahmab UR, Kumara NP, Deshpandea N, Prasannaa D, Senwara KR, Lakshmib UJ (2017) Bioorg Med Chem 25:4805CrossRefGoogle Scholar
  25. 25.
    Wade AR, Pawar HR, Biware MV, Chikate RC (2015) Green Chem 17:3879CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Biological Science and TechnologyUniversity of JinanJinanChina
  2. 2.Faculty of CeilandiaUniversity of BrasíliaBrasíliaBrazil

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