Synthesis, Characterization and Cytotoxic Activity of S-Benzyldithiocarbazate Schiff Bases Derived from 5-Fluoroisatin, 5-Chloroisatin, 5-Bromoisatin and Their Crystal Structures

  • Mohd Abdul Fatah Abdul MananEmail author
  • Karen A. Crouse
  • M. Ibrahim M. Tahir
  • Rozita Rosli
  • Fiona N.-F. How
  • David J. Watkin
  • Alexandra M. Z. Slawin
Original Paper


Schiff bases were prepared from S-benzyldithiocarbazate with 5-fluro-, 5-chloro- and 5-bromoisatin. All are potential tridentate nitrogen, oxygen, sulfur donors. They were found to be selectively active against MCF-7 cell line (Human non-metastatic mammary gland adenocarcinoma cell line). The bromide and fluoride compounds were the most active with IC50 values of 6.40 μM (2.6 μg/mL) and 9.26 μM (3.2 μg/mL) respectively while the chloride derivative was weakly active with an IC50 value of 38.69 μM (14.0 μg/mL). The cytotoxic activity of the halo substituted isatins against the breast cancer cell lines tested is in the order of Br > F > Cl. Planarity of the isatin ring in the Schiff bases can be arranged in the following order SB5FISA > SB5ClISA > SB5BrISA while the perpendicularity of the benzyl ring towards the dithiocarbazate plane can be ordered as follows, SB5FISA > SB5BrISA > SB5ClISA.

Graphical abstract

Schiff bases were prepared from S-benzyldithiocarbazate with 5-fluro-, 5-chloro- and 5-bromoisatin. They were found to be selectively active against MCF-7 cell line (Human non-metastatic mammary gland adenocarcinoma cell line) with the bromide compound was the most active with IC50 value of 6.40 μM (2.6 μg/mL).


Dithiocarbazate Schiff base Isatin MCF-7 Structure 



We thank the Department of Chemistry, Universiti Putra Malaysia for the provision of laboratory facilities. This work was funded by a grant from the Ministry of Science, Technology and Innovation under the Intensification of Research in Priority Area program (Grant no. 09-02-04-0755-EA001). Support from Universiti Teknologi MARA (UiTM) and the Ministry of Higher Education (MOHE) for MAFA Manan is also gratefully acknowledged.


  1. 1.
    Ali MA, Livingstone SE (1974) Coord Rev 13:101CrossRefGoogle Scholar
  2. 2.
    Battistoni C, Mattogno G, Monaci A, Trali F (1971) J lnorg Nucl Chem 33:3815CrossRefGoogle Scholar
  3. 3.
    Iskander MF, El Syed L (1971) J Inorg Nucl Chem 33:4253CrossRefGoogle Scholar
  4. 4.
    Glover V, Halket JM, Watkins PJ, Clow A, Goddwin BL, Sandler MJ (1988) Neurochemistry 51:656CrossRefGoogle Scholar
  5. 5.
    Bhattacharya SK, Glover V, McIntyre I, Oxenkrug G, Sandler M (1982) Neurosci Lett 92(2):218CrossRefGoogle Scholar
  6. 6.
    Bhattacharya SK, Mitra SK, Acharya SB (1991) J Psychopharmacol 5:202CrossRefGoogle Scholar
  7. 7.
    Gil-Turners MS, Hay ME, Fenical W (1989) Science 246:116CrossRefGoogle Scholar
  8. 8.
    Pandeya SN, Sriram D (1998) Acta Pharm Turc 40:33Google Scholar
  9. 9.
    Sarangapani M, Reddy VM (1994) Indian J Pharm Sci 56:174Google Scholar
  10. 10.
    Pignatello R, Panico A, Mazzane P, Pinizzotto MR, Garozzo A, Fumeri PM (1994) Eur J Med Chem 29:781CrossRefGoogle Scholar
  11. 11.
    Pandeya SN, Sriram D, Nath G, De Clercq E (1999) Indian J Pharm Sci 61:358Google Scholar
  12. 12.
    Pandeya SN, Sriram D, Nath G, De Clercq E (1999) Sci Pharm 67:103Google Scholar
  13. 13.
    Pandeya SN, Sriram D, Nath G, De Clercq E (1999) Pharm Acta Helv 74:11CrossRefGoogle Scholar
  14. 14.
    Varma RS, Nobles WL (1967) J Med Chem 10:972CrossRefGoogle Scholar
  15. 15.
    Pandeya SN, Yogeswari P, Sriram D, De Clercq E, Pannecouque C, Witvrouw M (1999) Chemotherapy 45:192CrossRefGoogle Scholar
  16. 16.
    Pandeya SN, Sriram D, Nath G, De Clercq E (2000) Eur J Med Chem 35:249CrossRefGoogle Scholar
  17. 17.
    Pandeya SN, Sriram D, Nath G, De Clercq E (2000) Drug Res 50:55Google Scholar
  18. 18.
    Imam SA, Varma RS (1975) Experientia 31(11):1287CrossRefGoogle Scholar
  19. 19.
    Varma RS, Khan IA (1977) Polish J Pharmacol Pharm 29(5):549Google Scholar
  20. 20.
    Sarciron SE, Audin P, Delebre I, Gabrion C, Petavy AF, Paris J (1983) J Pharm Sci 82:605CrossRefGoogle Scholar
  21. 21.
    Et-Sawi EA, Mostafa TB, Mostafa BB (1998) J Egypt Soc Parasitol 28:481Google Scholar
  22. 22.
    Chi KW, Furin GG, Bagrynskay IY, Gailov YV (2000) J Fluorine Chem 104(2):263CrossRefGoogle Scholar
  23. 23.
    Prenen H, Cools J, Mentens N, Folens C, Sciot R, Schoffski P, Van Oosterom A, Marynen P, Debiec-Rychter M (2006) Clin Cancer Res 8:2622CrossRefGoogle Scholar
  24. 24.
    Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, Ginsberg MS, Kim ST, Baum CM, DePrimo SE, Li JZ, Bello CL, Theuer CP, George DJ, Rini B (2006) J Clin Oncol 1:16CrossRefGoogle Scholar
  25. 25.
    Otwinowski Z, Minor W, Carter iCW, Sweet RM (eds) (1997) Processing of X-ray diffraction data collected in oscillation mode, methods enzymology, vol 276. Academic Press, New YorkGoogle Scholar
  26. 26.
    Altomare A, Cascarano G, Giacovazzo G, Guagliardi A, Burla MC, Polidori G, Camalli M (1994) J Appl Cryst 27:435Google Scholar
  27. 27.
    Watkin DJ, Prout CK, Carruthers JR, Betteridge PW. (1996) CRYSTALS, Issue 10 edn. Chemical Crystallography Laboratory, University of OxfordGoogle Scholar
  28. 28.
    Mosmann T (1983) J Immunol Methods 65:55CrossRefGoogle Scholar
  29. 29.
    Das M, Livingstone SE (1976) Inorg Chim Acta 19:5CrossRefGoogle Scholar
  30. 30.
    Ali MA, Mirza AH, Hamid MHSA, Bernhardt PV (2005) Polyhedron 24(3):383CrossRefGoogle Scholar
  31. 31.
    Pavia DL, Lampman GM, Kriz GS (2001) Introduction to organic spectroscopy. In: 1H nuclear magnetic resonance spectroscopy, 3rd edn. Brooks Cole Publishers, Philadelphia, pp 139Google Scholar
  32. 32.
    Akinchan NT, Drożdżewski PM, Holzer W (2002) J Mol Struct 641:17CrossRefGoogle Scholar
  33. 33.
    Langkilde A, Madsen D, Larsen S (2004) Acta Crystallogr Sect B 60:502CrossRefGoogle Scholar
  34. 34.
    Tarafder MTH, Khoo TJ, Crouse KA, Ali AM, Yamin BM, Fun HK (2002) Polyhedron 21:2691CrossRefGoogle Scholar
  35. 35.
    Raj SSS, Yamin BM, Yussof YA, Tarafder MTH, Fun HK, Crouse KA (2000) Acta Crystallogr Sect C 56:1236CrossRefGoogle Scholar
  36. 36.
    How FNF, Crouse KA, Tahir MIM, Tarafder MTH, Cowley AR (2008) Polyhedron 27:3325CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Mohd Abdul Fatah Abdul Manan
    • 1
    Email author
  • Karen A. Crouse
    • 2
  • M. Ibrahim M. Tahir
    • 2
  • Rozita Rosli
    • 3
  • Fiona N.-F. How
    • 2
  • David J. Watkin
    • 4
  • Alexandra M. Z. Slawin
    • 5
  1. 1.Faculty of Applied SciencesUniversiti Teknologi MARAShah AlamMalaysia
  2. 2.Department of Chemistry, Faculty of ScienceUniversiti Putra MalaysiaSerdangMalaysia
  3. 3.Department of Obstetrics and Gynaecology, Faculty of Medicine and Health SciencesUniversiti Putra MalaysiaSerdangMalaysia
  4. 4.Chemical Chemistry Research LaboratoryUniversity of OxfordOxfordUK
  5. 5.Molecular Structure Laboratory, School of ChemistryUniversity of St. AndrewsFifeUK

Personalised recommendations