Metal-based Anticancer Drugs Research Articles

A New Look into the Mode of Action of Metal-Based Anticancer Drugs.

The mode of action of Pt- and Pd-based anticancer agents (cisplatin and Pd2Spm) was studied by characterising their impact on DNA. Changes in conformation and mobility at the molecular level in hydrated DNA were analysed by quasi-elastic and inelastic neutron scattering techniques (QENS and INS), coupled to Fourier transform infrared (FTIR) and microRaman spectroscopies. Although INS, FTIR and Raman revealed drug-triggered changes in the phosphate groups and the double helix base pairing, QENS allowed access to the nanosecond motions of the biomolecule’s backbone and confined hydration water within the minor groove. Distinct effects were observed for cisplatin and Pd2Spm, the former having a predominant effect on DNA’s spine of hydration, whereas the latter had a higher influence on the backbone dynamics. This is an innovative way of tackling a drug’s mode of action, mediated by the hydration waters within its pharmacological target (DNA).

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The following topics are under this section: Empowering the Consumer in Heart Health Management Game Changers – Triple-Threat Start-up Technology to shake up both Food and Biomedical industries The Lab report - Researchers from National University of Singapore looking to discover novel metal-based anticancer drugs with reduced toxicity.

Single Spheroid Metabolomics: Optimizing Sample Preparation of Three-Dimensional Multicellular Tumor Spheroids.

Tumor spheroids are important model systems due to the capability of capturing in vivo tumor complexity. In this work, the experimental design of metabolomics workflows using three-dimensional multicellular tumor spheroid (3D MTS) models is addressed. Non-scaffold based cultures of the HCT116 colon carcinoma cell line delivered highly reproducible MTSs with regard to size and other key parameters (such as protein content and fraction of viable cells) as a prerequisite. Carefully optimizing the multiple steps of sample preparation, the developed procedure enabled us to probe the metabolome of single MTSs (diameter range 790 ± 22 µm) in a highly repeatable manner at a considerable throughput. The final protocol consisted of rapid washing of the spheroids on the cultivation plate, followed by cold methanol extraction. 13C enriched internal standards, added upon extraction, were key to obtaining the excellent analytical figures of merit. Targeted metabolomics provided absolute concentrations with average biological repeatabilities of <20% probing MTSs individually. In a proof of principle study, MTSs were exposed to two metal-based anticancer drugs, oxaliplatin and the investigational anticancer drug KP1339 (sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)]), which exhibit distinctly different modes of action. This difference could be recapitulated in individual metabolic shifts observed from replicate single MTSs. Therefore, biological variation among single spheroids can be assessed using the presented analytical strategy, applicable for in-depth anticancer drug metabolite profiling.

Five novel palladium(II) complexes of 8-hydroxyquinoline and amino acids with hydrophobic side chains: synthesis, characterization, cytotoxicity, DNA- and BSA-interaction studies

The side effects and resistance of metal-based anticancer drugs prompted us to synthesis a novel series of five Pd(II) complexes of the type [Pd(8-QO)(AA)]; where 8-QO = anion of 8-hydroxyquinoline and AA = anions of amino acids having nonpolar aliphatic side chain such as glycine (–H), alanine (–CH3), valine (–CH(CH3)2), leucine (–CH2–CH(CH3)2) and isoleucine (–CH(CH3)CH2–CH3). The complexes have been characterized with the help of FT-IR, UV–Vis, one and two-dimensional 1H-NMR, elemental analysis and conductivity measurements. On the basis of these characterization data, a four coordinated square planar geometry for all of these complexes have been proposed. The compounds were screened for their in vitro activities against human cancer cell line, MOLT-4 and their 50% inhibition concentration were ascertained by means of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Since four out of the five newly synthesized compounds were found to be more active than the standard anticancer drug, cisplatin, their detailed interaction with calf thymus DNA (as a target) and bovine serum albumin (BSA) (as a carrier) were also carried out by utilizing absorption spectra, fluorescence spectra and ethidium bromide displacement studies. In these experiments, several binding and thermodynamic parameters were also calculated. These results suggested that hydrogen binding and van der Waals forces play a major role in the interaction between metal complexes with CT-DNA and BSA. Communicated by Ramaswamy H. Sarma

Metal-Based Molecular Compounds: Structure, Analytical Properties, dsDNA Binding Studies and In Vitro Antiproliferative Activity on Selected Cancer Cell Lines

In this work, to contribute to research in the area of new chemotherapeutic agents, we attempted at obtaining new metal-based compounds as alternatives to the existing metal-based anticancer drugs. In this context, Cu(II), Zn(II) and Pt(II) metal-based complexes of pharmaceutically active compound, effective antineoplastic methotrexate (MTX), were synthesized, and their structures were elucidated by analytical (melting point, elemental analysis, conductivity, and solubility), spectroscopic (UV-Vis, IR, 1H NMR, LC-MS and ICP-OES) and thermal (TGA, DTA) methods. UV-Vis spectroscopy examined interactions of MTX pharmaceutically active substances and their metal-based compounds with the fish sperm double-stranded DNA (FS-dsDNA). Regarding the data obtained from spectroscopic measurements, it is understood that all compounds interact with FS-dsDNA. The antiproliferative activity of the active agent MTX and the newly synthesized metal-based compounds was investigated on C6 and He-La cells in comparison to the active anticancer agents present in the market using real-time cell analyzer with four different concentrations. Also, interactions of all compounds obtained with the double-stranded FS-dsDNA were studied using pencil graphite electrode (PGE) by monitoring changes in the signal of the guanine base. The associated surface morphology was examined by differential pulse voltammetry (DPV) and scanning electron microscopy (SEM) techniques.

Development of New Potential Anticancer Metal Complexes Derived from 2-Hydrazinobenzothiazole.

Due to the side effects of clinically approved anticancer drugs there is a great need to explore and develop new metal-based anticancer drug molecules of high efficiency with less or no side effects. To synthesize new metal complexes of 2-hydrazinobenzothiazole (hbt) and to investigate their potential anticancer characteristics. New five complexes; [VO(hbt)2SO4].4H2O (1), [Ru(hbt)2Cl3(H2O)] (2), [M(hbt)2Cl2] [M(II) = Pd (3), Pt (4)] and [Ag(hbt)2].NO3 (5) were prepared and their structure was investigated by means of FTIR, 1H NMR, ESI-MS and UV-Vis spectra, elemental and thermal analysis, magnetic and molar conductance measurements. The ligand and its complexes were examined as anticancer agents against Ehrlich ascites carcinoma (EAC) and human cancer cells (hepatocellular carcinoma Hep-G2, mammary gland breast cancer MCF-7 and colorectal carcinoma HCT-116). This feature is further supported by the DNAmetal complexes binding ability. In addition, anti-oxidation activity of the complexes was investigated. Complex (5) shows the highest anticancer activity with IC50 of 5.15, 9.9, 13.1 and 17.7 µg/mL for EAC, HePG-2, MCF-7 and HCT-116, respectively. Complexes (2) and (3) show promising cytotoxicity against EAC and HePG-2 cells with IC50 5.49 and 16.2 µg/mL, respectively. While, complexes (1) and (4) show optimistic cytotoxicity against EAC with IC50 of 9.63 and 11.25 µg/mL, respectively. The order of DNA binding ability of the complexes is (5) > (3) > (2) > (1) > (4). Among the five complexes, complex (5) shows the best anti-oxidation activity. Complex (5) showed the highest DNA binding ability, anti-oxidation and anticancer activities.

Design, Synthesis, DNA/HSA Binding, and Cytotoxic Activity of Half-Sandwich Ru(II)-Arene Complexes Containing Triarylamine-Thiosemicarbazone Hybrids.

Organoruthenium complexes are potent alternatives for platinum-based complexes because of their superior anticancer activity. In this investigation, a series of new Ru(II)-arene complexes with triarylamine–thiosemicarbazone hybrid ligands with higher anticancer activity than cisplatin are reported. The molecular structure of the ligands and complexes was confirmed spectroscopically and supported by single-crystal X-ray crystallography. These complexes adopted a three-leg piano stool geometry. All the Ru(II)-arene complexes were systematically investigated for their in vitro cytotoxicity against human cervical (HeLa S3), lung (A549) cancer, and human normal lung (IMR-90) cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Interestingly, a pyrrolidine-attached Ru(II)-benzene complex exhibited superior activity against cancer cells with low IC50 values, and colony formation study showed complete inhibition at 5 and 10 μM concentration. Furthermore, morphological changes assessed by acridine orange and propidium iodide staining revealed that the cell death occurred by apoptosis. In addition, the interaction between synthesized Ru(II)-arene complexes and DNA/protein was explored by absorption and emission spectroscopy methods. These synthesized new organoruthenium complexes can be used for developing new metal-based anticancer drugs.

Elucidation of the Mechanism of Action for Metal Based Anticancer Drugs by Mass Spectrometry-Based Quantitative Proteomics

The discovery of the anticancer activity of cisplatin and its clinical application has opened a new field for studying metal-coordinated anticancer drugs. Metal-based anticancer drugs, such as cisplatin, can be transported to cells after entering into the human body and form metal–DNA or metal–protein adducts. Then, responding proteins will recognize adducts and form stable complexes. The proteins that were binding with metal-based anticancer drugs were relevant to their mechanism of action. Herein, investigation of the recognition between metal-based anticancer drugs and its binding partners will further our understanding about the pharmacology of cytotoxic anticancer drugs and help optimize the structure of anticancer drugs. The “soft” ionization mass spectrometric methods have many advantages such as high sensitivity and low sample consumption, which are suitable for the analyses of complex biological samples. Thus, MS has become a powerful tool for the identification of proteins binding or responding to metal-based anticancer drugs. In this review, we focused on the mass spectrometry-based quantitative strategy for the identification of proteins specifically responding or binding to metal-based anticancer drugs, ultimately elucidating their mechanism of action.

Bioactive Salen-type Schiff Base Transition Metal Complexes as Possible Anticancer Agents.

Although metal-based anticancer drugs have been recognized as the most effective agents over the organic compounds, non-selectivity and high toxic effects have limited their applications in a way that only three Pt-analogues have progressed into clinical use. These problems have spurred chemists to develop different strategies based on alternative targets. This work focuses on predicting potency and mode of interactions of a series of salen type Schiff base transition metal complexes derived from meso-1,2-diphenyl-1,2-ethylenediamine, over some proteins (HDAC7, HDAC2, CatB, B-RAF kinase, TopII, RNR, TS, and rHA) using computational docking method, to be later considered as possible anticancer agents. The obtained results showed that all complexes exhibited higher affinity for HDAC7 than the other targets. Moreover, the bromo-derivatives of the copper compounds were more active on HDAC7 than the other derivatives. Such bromo compounds showed considerable interactions with Kinase, RNR, TS, and CatB. Contrary to Histone deacetylase (HAD)C7; HDAC2 was predicted to be relatively poor target. As expected, formation of the hydrophobic interactions between the metal complexes and the protein targets were essential for activity of the metal compounds. This study provides some more information for further optimizations and development of new metallodrugs as enzyme inhibitors for potential therapeutic agents.

Transition metal substituted sandwich-type polyoxometalates with a strong metal-C (imidazole) bond as anticancer agents.

Two novel sandwich-type polyoxometalates {Na0.7M5.3(H2O)2(imi)2(Himi)(SbW9O33)2}6- (M = NiII (1), CoII (2), imi = imidazole) containing a strong M-Cimi bond were synthesized by a tetragonal cluster [Na2Sb8W36O132(H2O)4]22- {Sb8W36} precursor. Compound 1 was highly cytotoxic against gastric cancer cells by arresting the cell cycle in the S-phase and inducing cell apoptosis.

Heart-cut 2DSEC-RP-LC-ICP-MS as a screening tool in metal-based anticancer research

Screening tool for metal-based anticancer drugs enabled by on-line heart-cut two-dimensional liquid chromatography combined with ICP-MS (2DLC-ICP-MS).

Anti-cancer study and whey protein complexation of new lanthanum(III) complex with the aim of achieving bioactive anticancer metal-based drugs

In this study, a new lanthanum (III)-amino acid complex utilizing cysteine has been synthesized and characterized. The anticancer activities of the prepared La(III) complex against MCF-7 cell lines were studied. Results of MTT assay showed that at all three incubation times, the cytotoxic effect of prepared La(III) complex on MCF-7 breast cancer cell lines displays a time- and dose-dependent inhibitory effects. The interactions of the La(III) complex with two whey proteins (bovine serum albumin, BSA, and Bovine β-lactoglobulin, βLG) have been explored by using spectroscopic and molecular dicking methods. The obtained results indicated that La(III) complex strongly quenched the fluorescence of two carrier proteins in static quenching mode and also, BSA hah stronger binding affinity toward studied complex than βLG whit binding constant values of KBSA-La Complex ∼ 0.11 × 104 M−1 and KβLG-La Complex ∼ 0.63 × 103 M−1 at 300 K. The thermodynamic parameters revealed the contribution of hydrogen bond and Vander Waals interactions in both systems. The distances of the La(III) complex whit whey proteins were calculated using Förster energy transfer theory and proved existence of the energy transfer between two proteins and prepared La(III) complex with a high probability. FT-IR and UV–Vis absorption measurements indicated that the binding of the La(III) to BSA and βLG may induce conformational and micro-environmental changes of the proteins. The docking results indicate that the La(III) complex bind to residues located in the site II of BSA and second site of βLG.Communicated by Ramaswamy H. Sarma

Investigation of binding behavior of important metal ions to thioredoxin reductase using mobility-shift affinity capillary electrophoresis: A preliminary insight into the development of new metal-based anticancer drugs

Thioredoxin reductase (TrxR) is a redox enzyme that is found to be elevated in a variety of tumors and its inhibition has been proved to be a new approach for the treatment of cancer. In this study, the binding behaviors of some metal ions on TrxR have been evaluated using mobility-shift affinity electrophoresis. Eighteen medicinally important metal ions from soft, borderline and hard categories were selected for the screening. This study was based on the fact that, overall mass, charge and size of a protein changes after interaction with charged ligands such as metal ions, which affects the electrophoretic movement of the analyte protein under the influence of electroosmotic flow. This alteration in electrophoretic mobility of the analyte is proportional to the strength of interaction between the two species and is utilized to calculate the binding results. The mobility ratio (R) of an EOF marker (injected in same run) and the analyte enzyme was determined and the binding result was expressed as the normalized difference of the mobility ratios of test enzyme with and without metal ion (ΔR/Rf) and its confidence interval. The method showed excellent precision, as the % RSD of mobility ratios of replicate runs (n = 6) for most of the enzyme-metal ion pair was found to be <1%. Six out of eighteen tested metal ions including Ir3+, Ag+, Os3+, Cr3+, Fe2+ and Rh3+ showed significant binding interactions (ΔR/Rf ≥ ±0.01), while for others, it was found to be weak or insignificant. Among all the tested metal ions, Ir3+ (ΔR/Rf = −0.27065 ± 0.00818) showed the strongest interaction followed by Ag+ (ΔR/Rf = −0.09821 ± 0.00783), Fe2+ (ΔR/Rf = −0.0482 ± 0.00701), Os3+ (ΔR/Rf = −0.04382 ± 0.00751), Cr2+ (ΔR/Rf = −0.04093 ± 0.01206) and Rh3+ (ΔR/Rf = −0.01455 ± 0.00857). The values of ΔR/Rf obtained for most of the enzyme-metal ion pair were negative, suggesting the multifaceted complexation behavior of metal ions, as they get coordinated with surrounding anions after initial binding with the enzyme. As a result, the overall charge on the enzyme becomes more negative. Significant interactions of the enzyme with some metal ions suggested that the drugs based on these metal ions may prove to be potential inhibitor of the enzyme, however, it would be interesting to evaluate that how these interactions would affect the function and stability of the enzyme.

Investigating the biological potency of novel lanthanum(III) amino acid complex: MCF-7 breast cancer cell line, BSA and β-LG as targets

With the aim of achieving bioactive anticancer metal-based drugs, a new lanthanum(III) complex using tyrosine amino acid was synthesized and characterized. The anticancer activities of [La(Tyr)3(OH2)3] complex against MCF-7 cell lines were studied and revealed that it can inhibit breast cancer cell lines with the IC50 value of 21 µM following 72 h exposure. The interaction of the La(III) complex with two model proteins, bovine serum albumin (BSA) and β-lactoglobulin (β-LG), was studied using biophysical as well as computational techniques. The fluorescence studies showed that the interaction of the La(III) complex with whey proteins caused strong fluorescence quenching of both proteins through static quenching mechanism and the La(III) complex interacted with BSA and β-LG with moderate binding affinity (KBSA–La complex = 0.50(± 0.1) × 104 M− 1 and Kβ-LG–La complex = 0.15(± 0.1) × 103 M− 1 at 310 K). According to the obtained thermodynamic parameters, hydrogen bonds and van der Waals interactions play a major role for BSA–complex and β-LG–complex associations. UV–Vis results showed that the binding of prepared La(III) complex to each protein induced conformational changes in the protein. The distances of the La(III) complex with the proteins were calculated using Forster energy transfer theory and proved the existence of energy transfer between two proteins and prepared La(III) complex with a high probability. UV–Vis absorption studies indicated that the binding of the La(III) to BSA and β-LG may induce conformational and micro-environmental changes of the proteins. The docking results indicate that the La(III) complex bind to residues located in the site II of BSA and second site of β-LG.

Critical assessment of different methods for quantitative measurement of metallodrug-protein associations

Quantitative screening for potential drug–protein binding is an essential step in developing novel metal-based anticancer drugs. ICP–MS approaches are at the core of this task; however, many applications lack in the capability of large-scale high-throughput screenings and proper validation. In this work, we critically discuss the analytical figures of merit and the potential method-based quantitative differences applying four different ICP–MS strategies to ex vivo drug–serum incubations. Two candidate drugs, more specifically, two Pt(IV) complexes with known differences of binding affinity towards serum proteins were selected. The study integrated centrifugal ultrafiltration followed by flow injection analysis, turbulent flow chromatography (TFC), and size exclusion chromatography (SEC), all combined with inductively coupled plasma-mass spectrometry (ICP–MS). As a novelty, for the first time, UHPLC SEC-ICP–MS was implemented to enable rapid protein separation to be performed within a few minutes at > 90% column recovery for protein adducts and small molecules.Graphical abstractQuantitative screening for potential drug–protein binding is an essential step in developingnovel metal-based anticancer drugs

DNA-BSA interaction, cytotoxicity and molecular docking of mononuclear zinc complexes with reductively cleaved N2S2 Schiff base ligands

The synthesis of three potentially tetradentate, N2S2 Schiff-base-ligands, containing a disulfide bond, LThioSSLThio(L1), LBrSSLBr (L2) and LDiMeOSSLDiMeO (L3) are reported. These ligands undergo reductive disulfide bond scission upon reaction with PPh3 in the presence of Zn2+ ion. [LDiOMeS]−, [LThioS]− and [LBrS]− are the resulting bidentate thiolate-imine anions respectively, which upon reaction with Zn2+ produce three new zinc(II) complexes: [Zn(LThioSN)2] (1), [Zn(LBrSN)2] (2) and [Zn(LDiOMeSN)2] (3). The structures of (L1) and 1–3 complexes were determined by X-ray diffraction. The interaction of 1–3 with CT-DNA have been investigated by absorption, emission, and CD spectroscopic methods and thermal denaturation measurements. The resulting data reveal that 1–3 show effective binding to CT-DNA (Kb = 2.2 × 104 to 1 × 105 L mol−1). The binding mode of DNA with 1–3 has also been investigated by molecular docking. The protein binding ability of 1–3 has been tested by monitoring the tryptophan emission intensity using BSA as a model protein. The quenching mechanism of BSA by the zinc complexes is static (kq = 1.66 to 3.4 × 1013 L mol−1 s−1). It is remarkable that 1–3 exhibit effective cytotoxicity against two human tumour cell lines (HeLa and MCF-7). The potent cytotoxic effects of 2 and 3, with IC50 values of 19.93 and 20.11 respectively, are higher relative to clinically used cisplatin (IC50 = 23.50) against the MCF-7 cell line, indicating that 2 and 3 may have the potential to act as effective metal-based anticancer drugs.

Structure-activity relationships of anticancer ruthenium(II) complexes with substituted hydroxyquinolines

8-Hydroxyquinolines (HQ), including clioquinol, possess cytotoxic properties and are widely used as ligands for metal-based anticancer drug research. The number and identity of substituents on the HQ can have a profound effect on activity for a variety of inorganic compounds. Ruthenium complexes of HQ exhibit radically improved potencies, and operate by a new, currently unknown, mechanism of action. To define structure-activity relationships (SAR), a family of 22 Ru(II) coordination complexes containing mono-, di- and tri-substituted hydroxyquinoline ligands were synthesized and their biological activity evaluated. The complexes exhibited promising cytotoxic activity against a cancer cell line, and the SAR data revealed the 2- and 7-positions as key sites for the incorporation of halogens to improve potency. The Ru(II) complexes potently inhibited translation, as demonstrated by an in-cell translation assay. The effects were seen at 2–15-fold higher concentrations than those required to observe cytotoxicity, suggesting that prevention of protein synthesis may be a primary, but not the exclusive mechanism for the observed cytotoxic activity.

Novel platinum-based anticancer drug: a complete vibrational study.

The introduction of cisplatin to oncology, in the 1970s, marked the onset of the search for novel and improved metal-based anticancer drugs. Polynuclear PtII and PdII complexes with linear alkylamines as bridging ligands are a class of potential antineoplastic agents that have shown promising cytotoxicity against low-prognosis human cancers, such as metastatic breast adenocarcinoma and osteosarcoma. The present study reports an analysis of [μ-N,N'-bis(3-aminopropyl)butane-1,4-diamine-κ4N,N':N'',N''']bis[dichloridoplatinum(II)], [Pt2Cl4(C10H26N4)], denoted Pt2Spm (Spm is spermine), by vibrational spectroscopy coupled to theoretical calculations. Within the latter, the Density Functional Theory (DFT - mPW1PW/6-31G*) and Effective Core Potential (ECP - LANL2DZ) approaches were used, in order to ensure the most accurate representation of the molecule and achieve a maximum agreement with the experimental data. The solid-state geometry of Pt2Spm corresponds to Ci symmetry, displaying 132 vibrational modes. A complete assignment of the experimental vibrational profile of the system was attained through the combined application of complementary Raman, FT-IR and Inelastic Neutron Scattering (INS) techniques. INS allowed an unequivocal identification of the CH2 and NH2 rocking modes, not clearly detected by the optical techniques, while Raman measurements led to a clear discrimination of the Pt-N stretching frequencies from the two distinct Pt-N moieties within the chelate. The metal-to-metal distances calculated for the molecule under study were found to allow the establishment of effective inter- and intrastrand crosslinks with DNA. These results will hopefully help to clarify the mode of action of the compound, at the molecular level, contributing to the development of improved cisplatin-like chemotherapeutic drugs having a higher efficacy and specificity coupled to lower acquired resistance and deleterious side effects.

The Deceptively Similar Ruthenium(III) Drug Candidates KP1019 and NAMI-A Have Different Actions. What Did We Learn in the Past 30 Years?

The general interest in anticancer metal-based drugs and some encouraging pharmacological results obtained at the beginning of the investigations on innovative Ru-based drugs triggered a lot of attention on NAMI-A and KP1019, the two Ru(III) coordination compounds that are the subject of this review. This great attention led to a considerable amount of scientific results and, more importantly, to their eventual admission into clinical trials. Both complexes share a relatively low systemic toxicity that allows reaching rather high dosages, comparable to those of carboplatin. Soon it became evident that NAMI-A and KP1019, in spite of their structural similarity, manifest very distinct chemical and biological properties. The pharmacological performances qualified KP1019 mainly as a cytotoxic drug for the treatment of platinum-resistant colorectal cancers, whereas NAMI-A gained the reputation of a potential anticancer drug with negligible effects on the primary tumor but a pronounced ability to affect metastases. We believe that a strictly comparative exam of NAMI-A and KP1019, based on the substantial body of studies accomplished since their discovery almost 30 years ago, might be an useful exercise, both for assessing the state of the art in terms of biological and clinical profiles, and of the inherent mechanisms, and for envisaging possible future developments in the light of past achievements.

Chirality in metal-based anticancer agents.

Chiral natural biological molecules, such as nucleic acids and proteins, guide the research of chiral compounds. Chiral metal-based drugs are currently an interesting and rapidly growing field in anticancer research. This perspective focuses on chiral metal compounds with application in cancer chemotherapy. The different chiral metal-based anticancer agents and the extent to which the chiral resolution affects their biological properties are discussed. This perspective will aid the design of new potent and efficient chiral metal-based anticancer drugs that exploit their unique properties combined with their potential selectivity toward targeted chiral biomolecules.