Mitochondria as a target of third row transition metal-based anticancer complexes

Olelewe, Chibuzor; Awuah, Samuel G.

doi:10.1016/j.cbpa.2022.102235

“…Another instance is that copper (II) compounds with either thiosemicarbazone or phenanthroline-phenazine ligand [171][172] exhibit superior anti-tumour activity when compared to metallodrugs or cisplatin [173]. This is mediated by hydrolytic mitochondrial pathways [7] that cleave DNA by oxidatively inducing intrinsic reactive oxygen species (ROS) [174]. Thiosemicarbazone ligands are tridentate [175] structures that comprise many compounds of R1R2 C=N-NH-(C=S)-N R3R4 [58].…”

Section: Figure 3 Hydrolysis and Autophagy Degradation Mechanisms Of ...mentioning

confidence: 99%

“…Among them, the most well-known is platinum-based drugs (PBD) such as cisplatin, carboplatin, and oxaliplatin, which are the most commonly used to treat cancer [4]. PBD in general or cisplatin in particular was approved in 1978, and it is the most preferable drug candidate [5] for a wide range of human diseases in chemotherapeutic applications [6][7]. As a result, this triumph has had a large impact on cancer treatment regimens [8] and influenced the discovery of a new MBD [9].…”

Section: Introductionmentioning

confidence: 99%

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Zaidi¹,

Miskon²

2023

Preprint

0

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Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands’ roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.

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“…Another instance is that copper(II) compounds with either thiosemicarbazone or phenanthroline–phenazine ligand [ 172 , 173 ] exhibit superior anti-tumour activity when compared to metallodrugs or cisplatin [ 174 ]. This is mediated by hydrolytic mitochondrial pathways [ 7 ] that cleave DNA by oxidatively inducing intrinsic reactive oxygen species (ROS) [ 175 ]. Thiosemicarbazone ligands are tridentate [ 176 ] structures that comprise many compounds of R1R2 C=N-NH-(C=S)-N R3R4 [ 55 ].…”

Section: Ligand Degradation Properties In Anti-chemoresistancementioning

confidence: 99%

“…Among them, the most well-known are platinum-based drugs (PBD) such as cisplatin, carboplatin, and oxaliplatin, which are the most commonly used to treat cancer [ 4 ]. PBD in general or cisplatin in particular was approved in 1978, and it is the most preferable drug candidate [ 5 ] for a wide range of human diseases in chemotherapeutic applications [ 6 , 7 ]. As a result, this triumph has had a large impact on cancer treatment regimens [ 8 ] and influenced the discovery of a new MBD [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Zaidi

¹

,

Miskon

²

2023

Molecules

15

0

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Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands’ roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy.

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“…Coordination compounds (CCs) have a more important place in chemistry as functional materials owing to their exceptional structural arrangements ( Kilpin and Dyson, 2013 ; Renfrew, 2014 ). CCs have a wide range of applications, especially in medicine (diagnosis and treatment), biology, and therapeutics ( Renfrew, 2014 ; Kasprzak et al, 2015 ; Boros et al, 2020 ; Karges et al, 2021 ; Damena et al, 2022 ; Olelewe and Awuah, 2023 ). As a result, interest in metal-based therapeutic agents is growing in the bioinorganic chemistry era due to the emergence of clinical trials with various mechanisms of action that could potentially provide new chemotherapeutic approaches to disease management ( Boros et al, 2020 ; Damena et al, 2022 ; Scalese et al, 2022 ; Kacsir et al, 2023 ; Olelewe and Awuah, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Organic–inorganic hybrid salt and mixed ligand Cr(III) complexes containing the natural flavonoid chrysin: Synthesis, characterization, computational, and biological studies

Alem

¹

,

Desalegn

²

,

Damena³

et al. 2023

Front. Chem.

1

0

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Organic–inorganic hybrid salt and mixed ligand Cr(III) complexes (Cr1 and Cr2) containing the natural flavonoid chrysin were synthesized. The metal complexes were characterized using UV-Vis, Fourier-transform infrared, MS, SEM-EDX, XRD, and molar conductance measurements. Based on experimental and DFT/TD-DFT calculations, octahedral geometries for the synthesized complexes were suggested. The powder XRD analysis confirms that the synthesized complexes were polycrystalline, with orthorhombic and monoclinic crystal systems having average crystallite sizes of 21.453 and 19.600 nm, percent crystallinities of 51% and 31.37%, and dislocation densities of 2.324 × 10−3 and 2.603 × 10−3 nm-2 for Cr1 and Cr2, respectively. The complexes were subjected to cytotoxicity, antibacterial, and antioxidant studies. The in vitro biological studies were supported with quantum chemical and molecular docking computational studies. Cr1 showed significant cytotoxicity to the MCF-7 cell line, with an IC50 value of 8.08 μM compared to 30.85 μM for Cr2 and 18.62 μM for cisplatin. Cr2 showed better antibacterial activity than Cr1. The higher EHOMO (−5.959 eV) and dipole moment (10.838 Debye) values of Cr2 obtained from the quantum chemical calculations support the observed in vitro antibacterial activities. The overall results indicated that Cr1 is a promising cytotoxic drug candidate.

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Mitochondria as a target of third row transition metal-based anticancer complexes

Cited by 16 publications

References 74 publications

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

Organic–inorganic hybrid salt and mixed ligand Cr(III) complexes containing the natural flavonoid chrysin: Synthesis, characterization, computational, and biological studies

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