Medicinal Utility of Thiosemicarbazones with Special Reference to Mixed Ligand and Mixed Metal Complexes: A Review

Abstract

Thiosemicarbazone complexes possess structural diversity and variable bonding patterns and potential biological implications and ion sensing abilities. The ability of the transition metals to acquire different geometries like octahedral, square planar and tetrahedral in different coordination environments has encouraged researchers to explore the coordination chemistry of thiosemicarbazone complexes which can also vary upon changing aldehydes and ketones, substituents attached to the carbonyl moiety, metal and its oxidation state, geometries, counter ions, presence of a solvent or additional molecules in the structures and substituents on the S or N(4)-atoms. This review aims to summarize recent developments in the synthesis and medicinal importance of thiosemicarbazone ligands and particular emphasis on their metal complexes. The mixed ligand-metal complexes have an important role to play in biological systems because a number of ligands try to combine with the same metal ions in vivo. Different ligands have different biological activities producing synergetic results and enhancing the potency of the formed complex. They also have a role to play in the storage and transport of substances, therefore the review article also covers the mixed ligand complexes of thiosemicarbazones with hetero ligands like 1,10-phenanthroline, pyridine, triphenyl phosphine etc. and their mechanistic action and medicinal benefits in recent years. The binuclear complexes of thiosemicarbazones with two different and same metal ions have also been explored here. Dinuclear complexes have been shown to possess interesting structures and in most cases, such complexes containing metal-metal bond also affects the complex's magnetic properties as well. It has been well discussed in the course of this study that metal complexes show enhanced biological activity than the free ligand or metal ion. The studies cited in the review have been sourced from publications indexed in known databases. Some of the recently explored structural alterations have been discussed in the paper and future substituted thiosemicarbazones and their complexes may emerge as multi-target inhibitors.

Synthesis, crystal structure and Hirshfeld analysis of N-ethyl-2-{3-methyl-2-[(2Z)-pent-2-en-1-yl]cyclopent-2-en-1-ylidene}hydrazinecarbothioamide

“…Several thiosemicarbazone derivatives have biological properties either as metal complexes or as non-coordinated molecules. For examples of thiosemicarbazone complexes with biological activity, see: Gupta et al (2022); Khan et al (2022);Monsur Showkot Hossain et al (2023); Parrilha et al (2022), which covers compounds for chemotherapy and medical diagnostic imaging combined, also referred to as theranostics, and Singh et al (2023). For a review of TSC complexes in the inhibition of topoisomerases, which are biological targets of prime importance in cancer research, see: Jiang et al (2023).…”

Transition Metal Complexes of Thiosemicarbazides, Thiocarbohydrazides, and Their Corresponding Carbazones with Cu(I), Cu(II), Co(II), Ni(II), Pd(II), and Ag(I)—A Review

“…Metal ions’ biological activity depends on their concentration; they can either enhance or harm the organism’s health [ 134 ]. Metal chelate has been investigated to have several biological actions, including antibacterial, anti-fungicidal, antiviral, and anti-cancer activity [ 135 , 136 ]. The biological activities of metal complexes differed from those of free ligands or metal ions, and increased or decreased activities with the non-complexed semicarbazones/thiosemicarbazones have been reported for several transition metal complexes [ 137 ].…”

Synthesis, Characterization,Computational Studies and Antimicrobial activity evaluation of Mixed ligand‐Metal complexes of selected thiosemicarbazones

“…The mixed ligand complexes have important role in biological systems as biological fluids involve mixed chelation with different ligands competing for same metal ions. Coordination of different ligands may produce synergetic effect and enhance the potential of the resulting complex [7] . A study reported Pd(II) complexes with isatin bisthiocarbohydrazone and triphenylphosphine and evaluated for their enzyme inhibitory action showing promising results [8] .…”

“…Coordination of different ligands may produce synergetic effect and enhance the potential of the resulting complex. [7] A study reported Pd(II) complexes with isatin bisthiocarbohydrazone and triphenylphosphine and evaluated for their enzyme inhibitory action showing promising results. [8] Combined experimental and computational study of mixed ligand-metal complexes of Ni(II), Co(II), Mn(II), and Zn(II) has been reported with tenoxicam drug and valine (Val).…”