Although the assortment of antifungal drugs is broad, the most commonly used agents have major drawbacks. Toxicity, serious side effects or the emergence of drug resistance are amongst them. New drugs and drug candidates under clinical trials do not guarantee better pharmacological parameters. These new medicines may appear effective; however; they may cause serious side effects. This current review is focused on the recent findings in the design of quinoline based antifungal agents. This field seems to be especially interesting as 8-hydroxyquinoline and its metal complexes have been well known as antifungals for years. Structural similarities between quinoline based antifungals and allylamines or homoallylamines, e.g. terbinafine is another interesting fact. Quinoline can be identified in a number of synthetic and natural antifungals, which indicates nature's preference for this fragment and identifying it as one of the so-called privileged structures. We have discussed new trends in the design of quinolines with antifungal properties, their possible targets and the structure activity relationships within the antifungal series developed.

Thiosemicarbazones (TSCs) are an interesting class of ligands that show a diverse range of biological activity, including anti-fungal, anti-viral and anti-cancer effects. Our previous studies have demonstrated the potent in vivo anti-tumor activity of novel TSCs and their ability to overcome resistance to clinically used chemotherapeutics. In the current study, 35 novel TSCs of 6 different classes were designed using a combination of retro-fragments that appear in other TSCs. Additionally, di-substitution at the terminal N4 atom, which was previously identified to be critical for potent anti-cancer activity, was preserved through the incorporation of an N4-based piperazine or morpholine ring. The anti-proliferative activity of the novel TSCs were examined in a variety of cancer and normal cell-types. In particular, compounds 1d and 3c demonstrated the greatest promise as anti-cancer agents with potent and selective anti-proliferative activity. Structure-activity relationship studies revealed that the chelators that utilized “soft” donor atoms, such as nitrogen and sulfur, resulted in potent anti-cancer activity. Indeed, the N,N,S donor atom set was crucial for the formation of redox active iron complexes that were able to mediate the oxidation of ascorbate. This further highlights the important role of reactive oxygen species generation in mediating potent anti-cancer activity. Significantly, this study identified the potent and selective anti-cancer activity of 1d and 3c that warrants further examination.

Aim: Glycoconjugated C 60 derivatives are of particular interest as potential cancer targeting agents due to an upregulated metabolic glucose demand, especially in the case of pancreatic adenocarcinoma and its dense stroma, which is known to be driven by a subset of pancreatic stellate cells. Materials & methods: Herein, we describe the synthesis and biological characterization of a hexakis-glucosamine C 60 derivative (termed 'Sweet-C 60 '). Results: Synthesized fullerene derivative predominantly accumulates in the nucleus of pancreatic stellate cells; is inherently nontoxic up to concentrations of 1 mg/ml; and is photoactive when illuminated with blue and green light, allowing its use as a photodynamic therapy agent. Conclusion: Obtained glycoconjugated nanoplatform is a promising nanotherapeutic for pancreatic cancer.

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In photodynamic therapy (PDT), a noninvasive anticancer treatment, visible light, is used as a magic bullet selectively destroying cancer cells by a photosensitizer that is nontoxic in the dark. Protoporphyrin IX (PpIX) is a natural photosensitizer synthesized in the cell, which is also a chelating agent that if bonded to Fe 2+ forms heme, a central component of hemoglobin. Therefore, xenobiotic iron chelators can disturb iron homeostasis, increasing the accumulation of PpIX, obstructing the last step of heme biosynthesis, and enhancing PDT efficiency. However, the attempts to use this promising idea have not proved to be hugely successful. Herein, we revisited this issue by analyzing the application of iron chelators highly toxic in the dark, which should have higher Fe 2+ affinity than the nontoxic chelators used so far. We have designed and prepared thiosemicarbazones (TSC) with the highest dark cellular cytotoxicity among TSCs ever reported. We demonstrate that compound 2 exerts powerful PDT enhancement when used in combination with 5-aminolevulinic acid (ALA), a precursor of PpIX.

This paper presents two water-soluble fullerene nanomaterials (HexakisaminoC60 and monoglucosamineC60, which is called here JK39) that were developed and synthesized as non-viral siRNA transfection nanosystems. The developed two-step Bingel–Hirsch reaction enables the chemical modification of the fullerene scaffold with the desired bioactive fragments such as d-glucosamine while keeping the crucial positive charged ethylenediamine based malonate. The ESI–MS and 13C-NMR analyses of JK39 confirmed its high Th symmetry, while X-ray photoelectron spectroscopy revealed the presence of nitrogen and oxygen-containing C–O or C–N bonds. The efficiency of both fullerenes as siRNA vehicles was tested in vitro using the prostate cancer cell line DU145 expressing the GFP protein. The HexakisaminoC60 fullerene was an efficient siRNA transfection agent, and decreased the GFP fluorescence signal significantly in the DU145 cells. Surprisingly, the glycofullerene JK39 was inactive in the transfection experiments, probably due to its high zeta potential and the formation of an extremely stable complex with siRNA.

Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30–40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors.

Two series of thiosemicarbazone-based iron chelators (twenty-seven compounds) were designed and synthesized using a microwave-assisted approach. Quinoline and halogenated phenyl were selected as parent scaffolds on the basis of a similarity search. The lipophilicity of the synthesized compounds was measured using HPLC and then calculated. Primary in vitro screening of the synthesized compounds was performed against eight pathogenic fungal strains. Only a few compounds showed moderate activity against fungi, and (E)-2-(quinolin-2-ylvinyl)-N,N-dimethylhydrazine-carbothioamide appeared to be more effective than fluconazole against most of the fungal strains tested. Antiproliferative activity was measured using a human colon cancer cell line (HCT-116). Several of the tested compounds showed submicromolar antiproliferative activity. Compounds were also tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The structure-activity relationships are discussed for all of the compounds.