The effect of histidine on the structure and antitumor activity of metal-5-halouracil complexes

Udai P. Singh, Ranjana Ghose, Animesh K. Ghose, Ajit Sodhi, Sukh Mahendra Singh, Rakesh K. Singh

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Abstract

The ternary complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) ions with 5-halouracils, viz., 5-fluorouracil (SFU), 5-chlorouracil (5ClU), and 5-bromouracil (5BrU) and the biologically important ligand L-histidine (HISD) have been synthesized and characterized by elemental analysis, conductance measurements, infrared spectra, electronic spectra, and magnetic moment (room temperature) measurements. On the basis of these studies, the structures of the complexes have been proposed. All these ternary complexes were screened for their antitumor activity against Dalton's lymphoma in C3H/He mice. It was found that only Mn(II)-5BrU-HISD, Co(II)-5BrU-HISD, Cu(II)-SCIU-HISD Cu(II)-5BrU-HISD, Zn(II)-5FU-HISD, and Zn(II)-5BrU-HISD complexes have significant antitumor activity with T/C > 125 % (where T and C represent mean lifespan of treated mice and control mice respectively). The Mn(II)-5FU-HISD, Co(II)-5FU-HISD, Co(II)-5CIU-HISD, Ni(II)-5CIU-HISD, Ni(II)-5BrU-HISD, and Zn(II)-5CIU-HISD complexes are also effective antitumor agents, with T/C > 115 %. The complexes that showed effective antitumor action in vivo were also found to inhibit 3H-thymidine incorporation (DNA replication) in Dalton's lymphoma cells in vitro.

Original languageEnglish (US)
Pages (from-to)325-339
Number of pages15
JournalJournal of Inorganic Biochemistry
Volume37
Issue number4
DOIs
StatePublished - 1989

Fingerprint

Histidine
Metals
Bromouracil
Fluorouracil
Lymphoma
Inbred C3H Mouse
Magnetic moments
DNA Replication
Temperature measurement
Antineoplastic Agents
Thymidine
Ions
Ligands
Infrared radiation

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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The effect of histidine on the structure and antitumor activity of metal-5-halouracil complexes. / Singh, Udai P.; Ghose, Ranjana; Ghose, Animesh K.; Sodhi, Ajit; Singh, Sukh Mahendra; Singh, Rakesh K.

In: Journal of Inorganic Biochemistry, Vol. 37, No. 4, 1989, p. 325-339.

Research output: Contribution to journalArticle

Singh, Udai P. ; Ghose, Ranjana ; Ghose, Animesh K. ; Sodhi, Ajit ; Singh, Sukh Mahendra ; Singh, Rakesh K. / The effect of histidine on the structure and antitumor activity of metal-5-halouracil complexes. In: Journal of Inorganic Biochemistry. 1989 ; Vol. 37, No. 4. pp. 325-339.
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AU - Sodhi, Ajit

AU - Singh, Sukh Mahendra

AU - Singh, Rakesh K.

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N2 - The ternary complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) ions with 5-halouracils, viz., 5-fluorouracil (SFU), 5-chlorouracil (5ClU), and 5-bromouracil (5BrU) and the biologically important ligand L-histidine (HISD) have been synthesized and characterized by elemental analysis, conductance measurements, infrared spectra, electronic spectra, and magnetic moment (room temperature) measurements. On the basis of these studies, the structures of the complexes have been proposed. All these ternary complexes were screened for their antitumor activity against Dalton's lymphoma in C3H/He mice. It was found that only Mn(II)-5BrU-HISD, Co(II)-5BrU-HISD, Cu(II)-SCIU-HISD Cu(II)-5BrU-HISD, Zn(II)-5FU-HISD, and Zn(II)-5BrU-HISD complexes have significant antitumor activity with T/C > 125 % (where T and C represent mean lifespan of treated mice and control mice respectively). The Mn(II)-5FU-HISD, Co(II)-5FU-HISD, Co(II)-5CIU-HISD, Ni(II)-5CIU-HISD, Ni(II)-5BrU-HISD, and Zn(II)-5CIU-HISD complexes are also effective antitumor agents, with T/C > 115 %. The complexes that showed effective antitumor action in vivo were also found to inhibit 3H-thymidine incorporation (DNA replication) in Dalton's lymphoma cells in vitro.

AB - The ternary complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) ions with 5-halouracils, viz., 5-fluorouracil (SFU), 5-chlorouracil (5ClU), and 5-bromouracil (5BrU) and the biologically important ligand L-histidine (HISD) have been synthesized and characterized by elemental analysis, conductance measurements, infrared spectra, electronic spectra, and magnetic moment (room temperature) measurements. On the basis of these studies, the structures of the complexes have been proposed. All these ternary complexes were screened for their antitumor activity against Dalton's lymphoma in C3H/He mice. It was found that only Mn(II)-5BrU-HISD, Co(II)-5BrU-HISD, Cu(II)-SCIU-HISD Cu(II)-5BrU-HISD, Zn(II)-5FU-HISD, and Zn(II)-5BrU-HISD complexes have significant antitumor activity with T/C > 125 % (where T and C represent mean lifespan of treated mice and control mice respectively). The Mn(II)-5FU-HISD, Co(II)-5FU-HISD, Co(II)-5CIU-HISD, Ni(II)-5CIU-HISD, Ni(II)-5BrU-HISD, and Zn(II)-5CIU-HISD complexes are also effective antitumor agents, with T/C > 115 %. The complexes that showed effective antitumor action in vivo were also found to inhibit 3H-thymidine incorporation (DNA replication) in Dalton's lymphoma cells in vitro.

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