Synthesizing a Cu^IIcomplex of tinidazole to tune the generation of the nitro radical anion in order to strike a balance between efficacy and toxic side effects

Abstract

Synthesis, characterization, enzyme assay, DNA binding and antimicrobial activity of a monomeric complex of CuII with tinidazole: significance of the controlled formation of the nitro radical anion.

Radio-Sensitizing Effects of CuII and ZnII Complexes of Ornidazole: Role of Nitro Radical Anion

“…21 This was an inspiration toward using complexes of Ornidazole to investigate their radio-sensitizing and/or cytotoxic attributes by bringing about a substantial decrease in RNO 2 •– formation and yet not compromising on efficacy. 26 − 28 , 33 Therefore, like in tirapazamine where 80% of drug metabolism is irrelevant in killing hypoxic cells, here also if we could show that complexes of Onz are better radio-sensitizers or hypoxic cytotoxins in spite of decreased RNO 2 •– , 26 − 28 , 33 the amount required for biological activity can be believed to be provided by the complexes. If the amount formed by Onz is much in excess of what is actually necessary, then there is the risk of undesirable neurotoxic side effects.…”

“… 26 − 28 , 33 Hence, use of complexes could have the advantage that excess RNO 2 •– would not be present in the system, leading to some clinical success with regard to toxic side effects. 26 − 28 Worth mentioning here is that the complexes are either better DNA-binding agents or DNA-damaging agents or both, following interaction of in situ generated RNO 2 •– with nucleobases and calf thymus DNA. 24 , 31 , 32 …”

A ZnIIcomplex of ornidazole with decreased nitro radical anions that is still highly active onEntamoeba histolytica

“…[6][7][8] Unfortunately, the same R-NO 2 c À ion is associated with the neurotoxic side effects, particularly when there is prolonged use of such molecules. [9][10][11] In such a situation, the aspects of neurotoxicity, or other forms of side effects, become a matter of concern, creating a need to control the generation of R-NO 2 c À . Too much generation of these reactive intermediates for this class of drugs and others can oen cause more harm than good.…”

“…[12][13][14][15] Hence, generating the correct amount or making it available through slow chemical release is becoming an important aspect of research. [10][11][12][13][14][15] This study reports the regulation of R-NO 2 c À for a specic cause, and this is achieved through the complex formation of one of the members of the 5-nitroimidazole family (ornidazole) with Zn II , which can likely generate the correct amount necessary for cytotoxicity of a biological target (axenic Entamoeba histolytica). In addition, what the drug compromises for by forming less free radical species, (R-NO 2 c À ), it makes up for by other attributes of complex formation.…”

Activity of CoII–Quinalizarin: A Novel Analogue of Anthracycline-Based Anticancer Agents Targets Human DNA Topoisomerase, Whereas Quinalizarin Itself Acts via Formation of Semiquinone on Acute Lymphoblastic Leukemia MOLT-4 and HCT 116 Cells

“…3,11−15 Therefore, it is necessary to strike a balance between therapeutic efficacy and toxic side effects with regard to the generation of these reactive intermediates. 16,17 Research has revealed that metal complexes of anthracyclines modulate the formation of semiquinone that helps to control cardiotoxicity. 18−20 However, in controlling the formation of semiquinone through complex formation in an attempt to check cardiotoxicity, efficacy of the molecule is often compromised.…”