A Comparison of In Vitro Studies between Cobalt(III) and Copper(II) Complexes with Thiosemicarbazone Ligands to Treat Triple Negative Breast Cancer.

Metal complexes have gained significant attention as potential anti-cancer agents. The anti-cancer activity of [Co(phen)2(MeATSC)](NO3)3•1.5H2O•C2H5OH 1 (where phen = 1,10-phenanthroline and MeATSC = 9-anthraldehyde-N(4)-methylthiosemicarbazone) and [Cu(acetylethTSC)Cl]Cl•0.25C2H5OH 2 (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide) was investigated by analyzing DNA cleavage activity. The cytotoxic effect was analyzed using CCK-8 viability assay. The activities of caspase 3/7, 9, and 1, reactive oxygen species (ROS) production, cell cycle arrest, and mitochondrial function were further analyzed to study the cell death mechanisms. Complex 2 induced a significant increase in nicked DNA. The IC50 values of complex 1 were 17.59 µM and 61.26 µM in cancer and non-cancer cells, respectively. The IC50 values of complex 2 were 5.63 and 12.19 µM for cancer and non-cancer cells, respectively. Complex 1 induced an increase in ROS levels, mitochondrial dysfunction, and activated caspases 3/7, 9, and 1, which indicated the induction of intrinsic apoptotic pathway and pyroptosis. Complex 2 induced cell cycle arrest in the S phase, ROS generation, and caspase 3/7 activation. Thus, complex 1 induced cell death in the breast cancer cell line via activation of oxidative stress which induced apoptosis and pyroptosis while complex 2 induced cell cycle arrest through the induction of DNA cleavage.

Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions.

In the present Special Issue on "Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions", an attempt has been made to include reports updating our knowledge of elements considered to be potential candidates for therapeutic applications and certain metal-containing species, which are extensively being examined towards their potential biomedical use due to their specific physicochemical properties [...].

Natural Phaeosphaeride A Derivatives Overcome Drug Resistance of Tumor Cells and Modulate Signaling Pathways.

In the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds on the activation of intracellular kinase cascades in A431 cells. MILLIPLEX MAP Multi-Pathway Magnetic Bead 9-Plex was used, which allowed for the simultaneous detection of the following nine phosphorylated protein markers of the main intracellular signaling pathways: a universal transcription factor that controls the expression of immune-response genes, apoptosis and cell cycle NFκB (pS536); cAMP-dependent transcription factor (CREB (pS133); mitogen-activated kinase p38 (pT180/pY182); stress-activated protein kinase JNK (pT183/pY185); ribosomal SK; transcription factors STAT3 (pS727) and STAT5A/B (pY694/699); protein kinase B (Akt) (pS473); and kinase regulated by extracellular signals ERK1/2 (pT185/pY187). The effect of various concentrations of PPA derivatives on the cell culture was studied using xCelligence RTCA equipment. The compounds were found to modulate JNK, ERK1/2, and p38 signaling pathways. The set of activated kinase cascades suggests that oxidative stress is the main probable mechanism of the toxic action of PPA derivatives.

Photodynamic Therapy of Inorganic Complexes for the Treatment of Cancer.

Photodynamic therapy (PDT) is a medicinal tool that uses a photosensitizer and a light source to treat several conditions, including cancer. PDT uses reactive oxygen species such as cytotoxic singlet oxygen (1 O2 ) to induce cell death in cancer cells. Chemotherapy has historically utilized the cytotoxic effects of many metals, especially transition metal complexes. However, chemotherapy is a systemic treatment so all cells in a patient's body are exposed to the same cytotoxic effects. Transition metal complexes have also shown high cytotoxicity as PDT agents. PDT is a potential localized method for treating several cancer types by using inorganic complexes as photosensitizing agents. This review covers several in vitro and in vivo studies, as well as clinical trials that reported on the anticancer properties of inorganic pharmaceuticals used in PDT against different types of cancer.

Sustaining a legacy in STEM the Prof. Tara Prasad Dasgupta way: The role of a mentor in our lives.

A mentoring relationship is a close, individualized relationship that develops over time between a graduate student and his/her adviser, and that includes both caring and guidance. Although there is a connection between mentors and advisers, not all mentors are advisers and not all advisers are mentors, but in this case, one adviser was a mentor to all. In his eloquent style, an inspirational mentor of underrepresented individuals in Jamaica by the name of Prof. Tara Prasad Dasgupta, AKA Prof., paved the way for many us who studied in the Department of Chemistry, The University of the West Indies, Mona Campus, Jamaica from 1974 until his passing on Monday, April 2020 due to the complications of the COVID-19. Based on his effective mentoring style and the fact that there is low percentage of underrepresented individuals who pursue Ph.D. degrees in the STEM subjects around the world, more so here in the U.S.A., Europe, and in the U.K., hence there is a need to write about a story on sustaining a legacy in STEM the Prof. Tara Prasad Dasgupta way, viz., the role of a mentor in our lives. As such, his style is documented here, along with testimonies from his former graduate students, including myself.

Next generation sequencing and functional pathway analysis to understand the mechanism of action of copper-tolfenamic acid against pancreatic cancer cells.

Anti-cancer activity of tolfenamic acid (TA) in preclinical models for pancreatic cancer (PaCa) is well established. Since the dosage for anti-cancer actions of TA is rather high, we recently demonstrated that IC50 values of Copper-TA are 30-80% less than TA in 12 cancer cell lines. This study elucidates the underlying mechanisms of Copper-TA in PaCa cells. Control and Copper-TA (IC50) treated PaCa cells were processed by next-generation sequencing (NGS) to determine differentially expressed genes using HTG EdgeSeq Oncology Biomarker panel. Ingenuity Pathway Analysis (IPA®) was used to identify functional significance of altered genes. The conformational studies for assessing the expression of key regulators and genes were conducted by Western blot and qPCR. IPA® identified several networks, regulators, as well as molecular and cellular functions associated with cancer. The top 5 molecular and cellular functions affected by Cu-TA treatment were cell death and survival, cellular development, cell growth and proliferation, cell cycle and cellular movement. The expression of top upstream regulators was confirmed by Western blot analysis while qPCR results of selected genes demonstrated that Copper-TA is efficacious at lower doses than TA. Results suggest that Copper-TA alters genes/key regulators associated with cancer and potentially serve as an effective anti-cancer agent.

Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand.

In this study, 9-anthraldehyde-N(4)-methylthiosemicarbazone (MeATSC) 1 and [Co(phen)2(O2CO)]Cl·6H2O 2 (where phen = 1,10-phenanthroline) were synthesized. [Co(phen)2(O2CO)]Cl·6H2O 2 was used to produce anhydrous [Co(phen)2(H2O)2](NO3)33. Subsequently, anhydrous [Co(phen)2(H2O)2](NO3)33 was reacted with MeATSC 1 to produce [Co(phen)2(MeATSC)](NO3)3·1.5H2O·C2H5OH 4. The ligand, MeATSC 1 and all complexes were characterized by elemental analysis, FT IR, UV-visible, and multinuclear NMR (1H, 13C, and 59Co) spectroscopy, along with HRMS, and conductivity measurements, where appropriate. Interactions of MeATSC 1 and complex 4 with calf thymus DNA (ctDNA) were investigated by carrying out UV-visible spectrophotometric studies. UV-visible spectrophotometric studies revealed weak interactions between ctDNA and the analytes, MeATSC 1 and complex 4 (Kb = 8.1 × 105 and 1.6 × 104 M-1, respectively). Topoisomerase inhibition assays and cleavage studies proved that complex 4 was an efficient catalytic inhibitor of human topoisomerases I and IIα. Based upon the results obtained from the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay on 4T1-luc metastatic mammary breast cancer cells (IC50 = 34.4 ±â€¯5.2 µM when compared to IC50 = 13.75 ±â€¯1.08 µM for the control, cisplatin), further investigations into the molecular events initiated by exposure to complex 4 were investigated. Studies have shown that complex 4 activated both the apoptotic and autophagic signaling pathways in addition to causing dissipation of the mitochondrial membrane potential (ΔΨm). Furthermore, activation of cysteine-aspartic proteases3 (caspase 3) in a time- and concentration-dependent manner coupled with the ΔΨm, studies implicated the intrinsic apoptotic pathway as the major regulator of cell death mechanism.

Copper-tolfenamic acid: evaluation of stability and anti-cancer activity.

The non-steroidal anti-inflammatory drug, Tolfenamic acid (TA) acts as an anti-cancer agent in several adult and pediatric cancer models. Copper (Cu) is an important element with multiple biological functions and has gained interest in medical applications. Recently, [Cu(TA)2(bpy)] (Cu-TA) has been synthesized in order to enhance therapeutic activity. In this study, we synthesized Cu-TA using an established method, characterized it by UV visible spectroscopy and Fourier-transform infrared spectroscopy (FTIR), and tested its anti-cancer activity using twelve cell lines representing various cancers, such as Ewing sarcoma, glioblastoma, medulloblastoma, neuroblastoma, pancreatic and prostate. The anti-proliferative activity of Cu-TA was determined at 48 h post-treatment and compared with the parental compound, TA. The IC50 values were calculated using GraphPad Prism software. The biological stability of Cu-TA was evaluated using twelve-month-old powder and six-month-old stock solution. Cardiomyocytes (H9C2) were used to test the cytotoxicity in non-malignant cells. Cu-TA showed higher anti-proliferative activity, and the IC50 values were 30 to 80% lower when compared with TA. H9C2 cells were non-responsive to Cu-TA, suggesting that it is selective towards malignant cells. Comparison of the twelve-month-old powder and six-month-old stock solution using the Panc1 cell line showed similar IC50 values (<5% variation), confirming the stability of Cu-TA either in powder or solution form. These findings demonstrate the potential of Cu-TA as an effective anti-cancer agent. Further studies to delineate the detailed mechanism of action of Cu-TA for specific cancer model are underway.

Towards lead compounds as anti-cancer agents via new phaeosphaeride A derivatives.

New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor studies were carried out on the U937, HCT-116, PC3, MCF-7, A549, К562, NCI-H929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 (IC50 = 0.59 ±â€¯0.27 µM) was observed to be 11 times more active than PPA (IC50 = 6.5 ±â€¯0.30 µM) towards the NCI-H929 cell line, with a therapeutic index of 18. Compound 6 was determined to be over half and 16 times more active than etoposide towards the NCI-H929 (IC50 = 0.9 ±â€¯0.05 µM) and A549 (IC50 = 100 ±â€¯7.0 µM) cell lines, respectively.

Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cells Growth via Downregulating Sp1 and Sp3 Transcription Factors.

BACKGROUND/AIMS: Targeting survivin, an anti-apoptotic protein and mitotic regulator, is considered as an effective therapeutic option for pancreatic cancer (PaCa). Tolfenamic acid (TA) showed anti-cancer activity in pre-clinical studies. A recent discovery demonstrated a copper(II) complex of TA (Cu-TA) can result in higher activity. In this study, the ability of Cu-TA to inhibit survivin and its transcription factors, Specificity protein (Sp) 1 and 3 in PaCa cell lines and tumor growth in mouse xenograft model were evaluated. METHODS: Cell growth inhibition was measured in MIA PaCa-2 and Panc1 cells for 2 days using CellTiter-Glo kit. Sp1, Sp3 and survivin expression (by Western blot and qPCR), apoptotic cells and cell cycle phase distribution (by flow cytometry) were evaluated. A pilot study was performed using athymic nude mice [treated with vehicle/Cu-TA (25 or 50 mg/kg) 3 times/week for 4 weeks. RESULTS: The IC50 value for Cu-TA was about half than TA.Both agents repressed the protein expression of Sp1/Sp3/survivin, Cu-TA was more effective than TA. Especially effect on survivin inhibition was 5.2 (MIA PaCa-2) or 6.4 (Panc1) fold higher and mRNA expression of only survivin was decreased. Apoptotic cells increased with Cu-TA treatment in both cell lines, while Panc1 showed both effect on apoptosis and cell cycle (G2/M) arrest. Cu-TA decreased the tumor growth in mouse xenografts (25 mg/kg: 48%; 50 mg/kg: 68%). Additionally, there was no change observed in mice body weights, indicating no overt toxicity was occurring. CONCLUSION: These results show that Cu-TA can serve as an effective survivin inhibitor for inhibiting PaCa cell growth.

Ferrocene-based anilides: synthesis, structural characterization and inhibition of butyrylcholinesterase.

Twenty-three compounds in two series of ferrocene-based anilides, with the general formula C5H5-Fe-C5H4-C6H4-NH-CO-C6H4-R (where R = H, F, Cl, CH3 and OCH3), have been successfully synthesized. The compounds were characterized by elemental analysis and FTIR, 1H NMR and 13C NMR spectroscopy. Two compounds (M07 and P09) were characterized by X-ray crystallography. Solid state studies indicate that ferrocene derivatives with the conformation of meta amide substituents engage in intermolecular H-bonding, which stabilizes the meta derivatives over their para analogues. The H-bonding takes place when the conformation of the ferrocene changes by rotation around the C-N bond, favoring interactions between two molecules in adjacent layers in the solid state. The potential importance of this H-bonding to the biological effects of these molecules was investigated using both experimental and computational studies. All the compounds were found to inhibit butyrylcholinesterase. The most active compound shows 50% inhibition at a concentration of 9 ± 0.2 µM, similar to the known drug galantamine (with an IC50 of 8 µM). Compounds with the ferrocene moiety meta to the amide linkage were consistently found to be slightly more active than the other structural isomers, suggesting that the H-bonding may only slightly increase the overall affinity for the protein. Computational studies confirmed the limited effects of the H-bonding in the presence and absence of water in the active site of butyrylcholinesterase, supporting the importance of hydrophobicity for inhibitors of this enzyme.

Polynuclear ruthenium organometallic complexes containing a 1,3,5-triazine ligand: synthesis, DNA interaction, and biological activity.

It is now well established that ruthenium complexes are attractive alternatives to platinum-based anticancer agents. Most of the ruthenium compounds currently under investigation contain a single metal center. The synthesis of multinuclear analogues may provide access to novel complexes with enhanced biological activity. In this work, we have synthesized a set of three trinuclear complexes containing organometallic ruthenium fragments-(arene)RuCl-coordinated to a 2,4,6-tris(di-2-pyridylamino)-1,3,5-triazine core [(Arene = benzene (2), p-cymene (1), or hexamethylbenzene (3)]. The interaction of the complexes with DNA was extensively studied using a variety of biophysical probes as well as by molecular docking. The complexes bind strongly to DNA with apparent binding constants ranging from 2.20 to 4.79 × 104 M-1. The binding constants from electronic absorption titrations were an order of magnitude greater. The mode of binding to the nucleic acid was not definitively determined, but the evidence pointed to some kind of non-specific electrostatic interaction. None of the complexes displayed any significant antimicrobial activity against the organisms that were studied and exhibited anticancer activity only at high (> 100 µM) concentration.

Coordination of different ligands to copper(II) and cobalt(III) metal centers enhances Zika virus and dengue virus loads in both arthropod cells and human keratinocytes.

Trace elements such as copper and cobalt have been associated with virus-host interactions. However, studies to show the effect of conjugation of copper(II) or cobalt(III) metal centers to thiosemicarbazone ligand(s) derived from either food additives or mosquito repellent such as 2-acetylethiazole or citral, respectively, on Zika virus (ZIKV) or dengue virus (serotype 2; DENV2) infections have not been explored. In this study, we show that four compounds comprising of thiosemicarbazone ligand derived from 2-acetylethiazole viz., (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide (acetylethTSC) (compound 1), a copper(II) complex with acetylethTSC as a ligand (compound 2), a thiosemicarbazone ligand-derived from citral (compound 3) and a cobalt(III) complex with a citral-thiosemicarbazone ligand (compound 4) increased DENV2 and ZIKV replication in both mosquito C6/36 cells and human keratinocytes (HaCaT cells). Treatment of both cell lines with compounds 2 or 4 showed increased dengue viral titers at all three tested doses. Enhanced dengue viral plaque formation was also noted at the tested dose of 100µM, suggesting higher production of infectious viral particles. Treatment with the compounds 2 or 4 enhanced ZIKV and DENV2 RNA levels in HeLa cell line and primary cultures of mouse bone marrow derived dendritic cells. Also, pre- or post treatments with conjugated compounds 2 or 4 showed higher loads of ZIKV or DENV2 envelope (E) protein in HaCaT cells. No changes in loads of E-protein were found in ZIKV-infected C6/36 cells, when compounds were treated after infection. In addition, we tested bis(1,10-phenanthroline)copper(II) chloride ([Cu(phen)2]Cl2, (compound 5) and tris(1,10-phenanthroline)cobalt(III) chloride ([Co(phen)3]Cl3, (compound 6) that also showed enhanced DENV2 loads. Also, we found that copper(II) chloride dehydrate (CuCl2·2H2O) or cobalt(II) chloride hexahydrate (CoCl2·6H2O) alone had no effects as "free" cations. Taken together, these findings suggest that use of Cu(II) or Co(III) conjugation to organic compounds, in insect repellents and/or food additives could enhance DENV2/ZIKV loads in human cells and perhaps induce pathogenesis in infected individuals or individuals pre-exposed to such conjugated complexes. IMPORTANCE: Mosquito-borne diseases are of great concern to the mankind. Use of chemicals/repellents against mosquito bites and transmission of microbes has been the topic of interest for many years. Here, we show that thiosemicarbazone ligand(s) derived from 2-acetylethiazole or citral or 1,10-phenanthroline upon conjugation with copper(II) or cobalt(III) metal centers enhances dengue virus (serotype 2; DENV2) and/or Zika virus (ZIKV) infections in mosquito, mouse and human cells. Enhanced ZIKV/DENV2 capsid mRNA or envelope protein loads were evident in mosquito cells and human keratinocytes, when treated with compounds before/after infections. Also, treatment with copper(II) or cobalt(III) conjugated compounds increased viral titers and number of plaque formations. These studies suggest that conjugation of compounds in repellents/essential oils/natural products/food additives with copper(II) or cobalt(III) metal centers may not be safe, especially in tropical and subtropical places, where several dengue infection cases and deaths are reported annually or in places with increased ZIKV caused microcephaly.

Kinetics and mechanism of the oxidation of a cobaloxime by sodium hypochlorite in aqueous solution: Is it an outer-sphere mechanism?

The kinetics and mechanism of the oxidation of [Co(dmgBF2)2(OH2)2] (where dmgBF2 = difluoroboryldimethylglyoximato) by sodium hypochlorite (NaOCl) were investigated by stopped-flow spectrophotometry at 450 nm over the temperature range of 10 °C ≤ θ ≤ 25 °C, pH range of 5.0 ≤ pH ≤ 7.8, and at an ionic strength of 0.60 M (NaCl). The pKa1 value for [Co(dmgBF2)2(H2O)2] was calculated as 5.27 ± 0.14 at I = 0.60 (NaCl). The redox process was dependent on pH and oxidant concentration in a complex manner, that is, kobs = ((k2[H+] + k1Ka)/([H+] + Ka))[OCl-]T, where at 25.3 °C, k1 was calculated as 3.54 × 104 M-1 s-1, and k2 as 2.51 × 104 M-1 cm-1. At a constant pH value, while varying the concentration of sodium hypochlorite two rate constants were calculated, viz., k'1 = 7.56 s-1 (which corresponded to a reaction pathway independent of the NaOCl concentration) and k'2 = 2.26 × 104 M-1 s-1, which was dependent on the concentration of NaOCl. From the variation in pH, [Formula: see text], and [Formula: see text] were calculated as 58 ± 16 kJ mol-1, 46 ± 1 kJ mol-1, 34 ± 55 J mol-1 K-1, and -6 ± 4 Jmol-1 K-1, respectively. The self-exchange rate constant, k11, for sodium hypochlorite (as ClO-) was calculated to be 1.2 × 103 M-1 s-1, where an outer-sphere electron transfer mechanism was assumed. A green product, [Co(dmgBF2)2(OH2)(OH)]·1.75NaOCl, which can react with DMSO, was isolated from the reaction at pH 8.04 with a yield of 13%.

Synthesis and characterization of azo-guanidine based alcoholic media naked eye DNA sensor.

DNA sensing always has an open meadow of curiosity for biotechnologists and other researchers. Recently, in this field, we have introduced an emerging class of molecules containing azo and guanidine functionalities. In this study, we have synthesized three new compounds (UA1, UA6 and UA7) for potential application in DNA sensing in alcoholic medium. The synthesized materials were characterized by elemental analysis, FTIR, UV-visible, 1H NMR and 13C NMR spectroscopies. Their DNA sensing potential were investigated by UV-visible spectroscopy. The insight of interaction with DNA was further investigated by electrochemical (cyclic voltammetry) and hydrodynamic (viscosity) studies. The results showed that compounds have moderate DNA binding properties, with the binding constants range being 7.2 × 103, 2.4 × 103 and 0.2 × 103 M-1, for UA1, UA6 and UA7, respectively. Upon binding with DNA, there was a change in colour (a blue shift in the λmax value) which was observable with a naked eye. These results indicated the potential of synthesized compounds as DNA sensors with detection limit 1.8, 5.8 and 4.0 ng µl-1 for UA1, UA6 and UA7, respectively.

Computational, electrochemical, and spectroscopic studies of two mononuclear cobaloximes: the influence of an axial pyridine and solvent on the redox behaviour and evidence for pyridine coordination to cobalt(i) and cobalt(ii) metal centres.

[Co(dmgBF2)2(H2O)2] (where dmgBF2 = difluoroboryldimethylglyoximato) was used to synthesize [Co(dmgBF2)2(H2O)(py)]·0.5(CH3)2CO (where py = pyridine) in acetone. The formulation of complex was confirmed by elemental analysis, high resolution MS, and various spectroscopic techniques. The complex [Co(dmgBF2)2(solv)(py)] (where solv = solvent) was readily formed in situ upon the addition of pyridine to complex . A spectrophotometric titration involving complex and pyridine proved the formation of such a species, with formation constants, log K = 5.5, 5.1, 5.0, 4.4, and 3.1 in 2-butanone, dichloromethane, acetone, 1,2-difluorobenzene/acetone (4 : 1, v/v), and acetonitrile, respectively, at 20 °C. In strongly coordinating solvents, such as acetonitrile, the lower magnitude of K along with cyclic voltammetry, NMR, and UV-visible spectroscopic measurements indicated extensive dissociation of the axial pyridine. In strongly coordinating solvents, [Co(dmgBF2)2(solv)(py)] can only be distinguished from [Co(dmgBF2)2(solv)2] upon addition of an excess of pyridine, however, in weakly coordinating solvents the distinctions were apparent without the need for excess pyridine. The coordination of pyridine to the cobalt(ii) centre diminished the peak current at the Epc value of the Co(I/0) redox couple, which was indicative of the relative position of the reaction equilibrium. Herein we report the first experimental and theoretical (59)Co NMR spectroscopic data for the formation of Co(i) species of reduced cobaloximes in the presence and absence of py (and its derivatives) in CD3CN. From spectroelectrochemical studies, it was found that pyridine coordination to a cobalt(i) metal centre is more favourable than coordination to a cobalt(ii) metal centre as evident by the larger formation constant, log K = 4.6 versus 3.1, respectively, in acetonitrile at 20 °C. The electrosynthesis of hydrogen by complexes and in various solvents demonstrated the dramatic effects of the axial ligand and the solvent on the turnover number of the respective catalyst.

The Use of Inorganic Compounds in Photodynamic Therapy: Improvements in Methods and Photosensitizer Design

Background: Nanotechnology has provided significant benefits to photodynamic therapy (PDT), which has revolutionized treatments of several diseases. The success of this versatile technique is governed by the sequential in situ generation of reactive oxygen species, after a suitable photosensitizer has been irradiated by a defined wavelength of light. While PDT provides a minimally-invasive and convenient method for the treatment of several afflictions, the efficiency of this therapeutic strategy still has potential for improvements. Several bodies of works within this realm have highlighted the use of inorganic compounds, which is pivotal for the development of photosensitizers (PSs), nanoparticles (NPs) and irradiation sources. Methods: The past decade of online patented reports based on PDT were reviewed. Results: The patented reports analyzed showcased the integration of nanomaterials and inorganic compounds into PDT. The patents were grouped according to the following categories, viz., "Nanoparticles in Photodynamic Therapy", "Photosensitizers Incorporating Various Metal Centers", and "Modifications to Light Delivery". Conclusion: PDT is a suitable treatment option for several diseases however there are several challenges and limitations. The incorporation of NPs in the field of PDT is an extremely promising avenue which can be utilized to improve the execution of PDT. Furthermore, the use of inorganic compounds was noted to be frequented in the development of PSs and NP conjugates. The patents presented addressed the associated problems with PDT but there still remains an opportunity for continued research efforts so that more clinical applications are possible.

A novel copper(II) complex identified as a potent drug against colorectal and breast cancer cells and as a poison inhibitor for human topoisomerase IIα.

A novel complex, [Cu(acetylethTSC)Cl]Cl•0.25C2H5OH 1 (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide), was shown to have anti-proliferative activity against various colon and aggressive breast cancer cell lines. In vitro studies showed that complex 1 acted as a poison inhibitor of human topoisomerase IIα, which may account for the observed anti-cancer effects.

Synthesis of natural phaeosphaeride A derivatives and an in vitro evaluation of their anti-cancer potential.

Derivatives of phaeosphaeride A (PPA) were synthesised and characterised; then anti-cancer studies were carried out on the A549 cancer cell line. It was found that the acetyl derivative (compound 3) displayed comparable in vitro cytotoxicity to that of PPA (EC50=49±7 µM and EC50=46±5 µM, respectively), while chloroacetyl derivative 6 (EC50=33±7 µM) was found to have better efficacy towards the A549 cancer cell line.