Heterocyclic (pyrazine)carboxamide Ru(ii) complexes: structural, experimental and theoretical studies of interactions with biomolecules and cytotoxicity.

Treatments of N-(1H-benzo[d]imidazol-2-yl)pyrazine-2-carboxamide (HL1) and N-(benzo[d]thiazol-2-yl)pyrazine-2-carboxamide carboxamide ligands (HL2) with [Ru(p-cymene)Cl2]2 and [Ru(PPh3)3Cl2] precursors afforded the respective Ru(ii) complexes [Ru(L1)(p-cymene)Cl] (Ru1), [Ru(L2)(p-cymene)Cl] (Ru2), [Ru(L1)(PPh3)2Cl] (Ru3), and [Ru(L2)(PPh3)2Cl] (Ru4). These complexes were characterized by NMR, FT-IR spectroscopies, mass spectrometry, elemental analyses, and crystal X-ray crystallography for Ru2. The molecular structure of complex Ru2 contains one mono-anionic bidentate bound ligand and display pseudo-octahedral piano stool geometry around the Ru(ii) atom. The interactions with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were investigated by spectroscopic techniques. The experimental binding studies suggest that complexes Ru1-Ru4 interact with DNA, primarily through minor groove binding, as supported by molecular docking results. Additionally, these complexes exhibit strong quenching of the fluorescence of tryptophan residues in BSA, displaying static quenching. The in vitro cytotoxicity studies of compounds Ru1-Ru4 were assessed in cancer cell lines (A549, PC-3, HT-29, Caco-2, and HeLa), as well as a non-cancer line (KMST-6). Compounds Ru1 and Ru2 exhibited superior cytotoxicity compared to Ru3 and Ru4. The in vitro cytotoxicity and selectivity of compounds Ru1 and Ru2 against A549, PC-3, and Caco-2 cell lines surpassed that of cisplatin.

The Cytotoxicity of Cotyledon orbiculata Aqueous Extract and the Biogenic Silver Nanoparticles Derived from the Extract.

Green synthesized silver nanoparticles (AgNPs) have become popular because of their promising biological activities. However, for most of these nanoparticles, the cytotoxic effects have not been determined and their safety is not guaranteed. In a previous study, we successfully synthesized AgNPs (Cotyledon-AgNPs) using an extract of Cotyledon orbiculata, a medicinal plant traditionally used in South Africa to treat skin conditions. Cotyledon-AgNPs were shown to have significant antimicrobial and wound-healing activities. Fibroblast cells treated with extracts of C. orbiculata and Cotyledon-AgNPs demonstrated an enhanced growth rate, which is essential in wound healing. These nanoparticles therefore have promising wound-healing activities. However, the cytotoxicity of these nanoparticles is not known. In this study, the toxic effects of C. orbiculata extract and Cotyledon-AgNPs on the non-cancerous skin fibroblast (KMST-6) were determined using in vitro assays to assess oxidative stress and cell death. Both the C. orbiculata extract and the Cotyledon-AgNPs did not show any significant cytotoxic effects in these assays. Gene expression analysis was also used to assess the cytotoxic effects of Cotyledon-AgNPs at a molecular level. Of the eighty-four molecular toxicity genes analysed, only eight (FASN, SREBF1, CPT2, ASB1, HSPA1B, ABCC2, CASP9, and MKI67) were differentially expressed. These genes are mainly involved in fatty acid and mitochondrial energy metabolism. The results support the finding that Cotyledon-AgNPs have low cytotoxicity at the concentrations tested. The upregulation of genes such as FASN, SERBF1, and MKI-67 also support previous findings that Cotyledon-AgNPs can promote wound healing via cell growth and proliferation. It can therefore be concluded that Cotyledon-AgNPs are not toxic to skin fibroblast cells at the concentration that promotes wound healing. These nanoparticles could possibly be safely used for wound healing.

Apoptotic effects of triterpenoids isolated from Pleiocarpa pycnantha leaves in cancer cells and molecular docking study of the interactions of camptothecin and ursolic acid with human caspase 3, caspase 9 and topoisomerase I.

The aim of this study was to examine the effects of triterpenes from Pleiocarpa pycnantha leaves on the induction of apoptotic signalling in human cells. The molecular mechanisms of triterpenes isolated from P. pycnantha leaves were investigated in vitro on HeLa, MCF-7, HT-29, and KMST-6 cells. The compounds activated several markers associated with apoptosis, viz., phosphatidylserine translocation, caspase activation, oxidative stress, and topoisomerase I inhibition. Compounds 1 and 5 were non-selective, whereas compounds 2, 3, and 4 showed potential as cancer-specific agents by selectively inducing apoptosis only on cancer cells. Theoretical studies on the interactions of compound 1 with caspases -3 and -9 and topoisomerase I were carried out through a molecular docking study and illustrated that compound 1 had an equal binding affinity with the caspases and topoisomerase I comparable to that of camptothecin. The cellular pathway activated by these compounds was dependent on the compound and the cell type.

Diagnostic and Therapeutic Approaches for Glioblastoma and Neuroblastoma Cancers Using Chlorotoxin Nanoparticles.

Glioblastoma multiforme (GB) and high-risk neuroblastoma (NB) are known to have poor therapeutic outcomes. As for most cancers, chemotherapy and radiotherapy are the current mainstay treatments for GB and NB. However, the known limitations of systemic toxicity, drug resistance, poor targeted delivery, and inability to access the blood-brain barrier (BBB), make these treatments less satisfactory. Other treatment options have been investigated in many studies in the literature, especially nutraceutical and naturopathic products, most of which have also been reported to be poorly effective against these cancer types. This necessitates the development of treatment strategies with the potential to cross the BBB and specifically target cancer cells. Compounds that target the endopeptidase, matrix metalloproteinase 2 (MMP-2), have been reported to offer therapeutic insights for GB and NB since MMP-2 is known to be over-expressed in these cancers and plays significant roles in such physiological processes as angiogenesis, metastasis, and cellular invasion. Chlorotoxin (CTX) is a promising 36-amino acid peptide isolated from the venom of the deathstalker scorpion, Leiurus quinquestriatus, demonstrating high selectivity and binding affinity to a broad-spectrum of cancers, especially GB and NB through specific molecular targets, including MMP-2. The favorable characteristics of nanoparticles (NPs) such as their small sizes, large surface area for active targeting, BBB permeability, etc. make CTX-functionalized NPs (CTX-NPs) promising diagnostic and therapeutic applications for addressing the many challenges associated with these cancers. CTX-NPs may function by improving diffusion through the BBB, enabling increased localization of chemotherapeutic and genotherapeutic drugs to diseased cells specifically, enhancing imaging modalities such as magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), optical imaging techniques, image-guided surgery, as well as improving the sensitization of radio-resistant cells to radiotherapy treatment. This review discusses the characteristics of GB and NB cancers, related treatment challenges as well as the potential of CTX and its functionalized NP formulations as targeting systems for diagnostic, therapeutic, and theranostic purposes. It also provides insights into the potential mechanisms through which CTX crosses the BBB to bind cancer cells and provides suggestions for the development and application of novel CTX-based formulations for the diagnosis and treatment of GB and NB in the future.

Anticancer, Antioxidant, and Catalytic Activities of Green Synthesized Gold Nanoparticles Using Avocado Seed Aqueous Extract.

Disposal of agricultural waste has a negative impact on the environment and human health and may contribute to the greenhouse effect. The field of nanotechnology could provide alternative solutions to upcycle agricultural wastes in a safer manner into high-end value products. Organic waste from plants contain biomaterials that could serve as reducing and capping agents in the synthesis of nanomaterials with enhanced activities for use in biomedical and environmental applications. Persea americana (avocado) is a fruit with a high nutritional value; however, despite its rich phytochemical profile, its seed is often discarded as waste. Therefore, this study aimed to upcycle avocado seeds through the synthesis of gold nanoparticles (AuNPs) and evaluate their anticancer, antioxidant, and catalytic activities. The biosynthesis of avocado seed extract (AvoSE)-mediated AuNPs (AvoSE-AuNPs) was achieved following the optimization of various reaction parameters, including pH, temperature, extract, and gold salt concentrations. The AvoSE-AuNPs were poly-dispersed and anisotropic, with average core and hydrodynamic sizes of 14 ± 3.7 and 101.39 ± 1.4 nm, respectively. The AvoSE-AuNPs showed excellent antioxidant potential in terms of ferric reducing antioxidant power (343.88 ± 0.001 µmolAAE/L), 2,2-diphenyl-1-picrylhydrazyl (128.80 ± 0.0159 µmolTE/L), and oxygen radical absorbance capacity (1822.02 ± 12.6338 µmolTE/L); significantly reduced the viability of Caco-2 and PC-3 cells in a dose-dependent manner; and efficiently reduced 4-nitrophenol (4-NP) to 4-aminophenol. This study demonstrated how avocado seeds, an agricultural waste, can be used as sources of new bioactive materials for the synthesis of AuNPs, which have excellent antioxidant, anticancer, and catalytic activities, showing AvoSE-AuNPs' versatility in various applications. In addition, the AvoSE-AuNPs exhibited good stability and recyclability during the catalytic activity, which is significant because some of the primary issues with the use of metallic NPs as catalysts are around the cost-effectiveness, recovery, and reusability of the catalyst.

Reports of Plant-Derived Nanoparticles for Prostate Cancer Therapy.

Plants have demonstrated potential in providing various types of phytomedicines with chemopreventive properties that can combat prostate cancer. However, despite their promising in vitro activity, the incorporation of these phytochemicals into the market as anticancer agents has been hindered by their poor bioavailability, mainly due to their inadequate aqueous solubility, chemical instability, and unsatisfactory circulation time. To overcome these drawbacks, it has been suggested that the incorporation of phytochemicals as nanoparticles can offer a solution. The use of plant-based chemicals can also improve the biocompatibility of the formulated nanoparticles by avoiding the use of certain hazardous chemicals in the synthesis, leading to decreased toxicity in vivo. Moreover, in some cases, phytochemicals can act as targeting agents to tumour sites. This review will focus on and summarize the following points: the different types of nanoparticles that contain individual phytochemicals or plant extracts in their design with the aim of improving the bioavailability of the phytochemicals; the therapeutic evaluation of these nanoparticles against prostate cancer both in vitro and in vivo and the reported mode of action and the different types of anticancer experiments used; how the phytochemicals can also improve the targeting effects of these nanoparticles in some instances; and the potential toxicity of these nanoparticles.

Green Synthesized sAuNPs as a Potential Delivery Platform for Cytotoxic Alkaloids.

The use of natural products as chemotherapeutic agents is well established. However, many are associated with undesirable side effects, including high toxicity and instability. Previous reports on the cytotoxic activity of pyrroloiminoquinones isolated from Latrunculid sponges against cancer cell lines revealed extraordinary activity at IC50 of 77nM for discorhabdins. Their general lack of selectivity against the cancer and normal cell lines, however, precludes further development. In this study, extraction of a South African Latrunculid sponge produced three known pyrroloiminoquinone metabolites (14-bromodiscorhabdin C (5), Tsitsikammamine A (6) and B (7)). The assignment of the structures was established using standard 1D and 2D NMR experiments. To mitigate the lack of selectivity, the compounds were loaded onto gold nanoparticles synthesized using the aqueous extract of a brown seaweed, Sargassum incisifolium (sAuNPs). The cytotoxicity of the metabolites alone, and their sAuNP conjugates, were evaluated together with the known anticancer agent doxorubicin and its AuNP conjugate. The compound-AuNP conjugates retained their strong cytotoxic activity against the MCF-7 cell line, with >90% of the pyrroloiminoquinone-loaded AuNPs penetrating the cell membrane. Loading cytotoxic natural products onto AuNPs provides an avenue in overcoming some issues hampering the development of new anticancer drugs.

Stage-specific treatment of colorectal cancer: A microRNA-nanocomposite approach.

Colorectal cancer (CRC) is among the leading causes of cancer mortality. The lifetime risk of developing CRC is about 5% in adult males and females. CRC is usually diagnosed at an advanced stage, and at this point therapy has a limited impact on cure rates and long-term survival. Novel and/or improved CRC therapeutic options are needed. The involvement of microRNAs (miRNAs) in cancer development has been reported, and their regulation in many oncogenic pathways suggests their potent tumor suppressor action. Although miRNAs provide a promising therapeutic approach for cancer, challenges such as biodegradation, specificity, stability and toxicity, impede their progression into clinical trials. Nanotechnology strategies offer diverse advantages for the use of miRNAs for CRC-targeted delivery and therapy. The merits of using nanocarriers for targeted delivery of miRNA-formulations are presented herein to highlight the role they can play in miRNA-based CRC therapy by targeting different stages of the disease.

Co-Treatment of Caco-2 Cells with Doxorubicin and Gold Nanoparticles Produced from Cyclopia intermedia Extracts or Mangiferin Enhances Drug Effects.

Mangiferin (MGF) is a natural and valuable polyphenol found in significant levels in many plant species, including Cyclopia intermedia (C. intermedia). In a previous study, we synthesized gold nanoparticles (AuNPs) using MGF and a water extract of C. intermedia and reported that these AuNPs have very low cytotoxicity toward a human colon cancer (Caco-2) cell line. Although the study also showed that these biogenic AuNPs in combination with doxorubic (DOX) significantly augmented the cytotoxic effects of DOX in Caco-2 cells, the mechanism of the enhanced effect was not fully understood, and it was also not known if other cell lines would be sensitive to this co-treatment. In the present study, we examined the cytotoxicity of the co-treatment in Caski, HeLa, HT-29, KMST-6 and MDA-321 cell lines. Additionally, we investigated the mechanistic effects of this co-treatment in Caco-2 cells using several assays, including the adenosine triphosphate (ATP), the oxidative stress, the mitochondrial depolarization, the colony formation, the APOPercentage and the DNA fragmentation assays. We also assessed the intracellular uptake of the biogenic AuNPs. The study showed that the biogenic AuNPs were effectively taken up by the cancer cells, which, in turn, may have enhanced the sensitivity of Caco-2 cells to DOX. Moreover, the combination of the biogenic AuNPs and DOX caused a rapid depletion of ATP levels, increased mitochondrial depolarization, induced apoptosis, reduced the production of reactive oxygen species (ROS) and inhibited the long-term survival of Caco-2 cells. Although the study provided some insight into the mechanism of cytotoxicity induced by the co-treatment, further mechanistic and molecular studies are required to fully elucidate the enhanced anticancer effect of the co-treatment.

Biomedical Applications of Plant Extract-Synthesized Silver Nanoparticles.

Silver nanoparticles (AgNPs) have attracted a lot of interest directed towards biomedical applications due in part to their outstanding anti-microbial activities. However, there have been many health-impacting concerns about their traditional synthesis methods, i.e., the chemical and physical methods. Chemical methods are commonly used and contribute to the overall toxicity of the AgNPs, while the main disadvantages of physical synthesis include high production costs and high energy consumption. The biological methods provide an economical and biocompatible option as they use microorganisms and natural products in the synthesis of AgNPs with exceptional biological properties. Plant extract-based synthesis has received a lot of attention and has been shown to resolve the limitations associated with chemical and physical methods. AgNPs synthesized using plant extracts provide a safe, cost-effective, and environment-friendly approach that produces biocompatible AgNPs with enhanced properties for use in a wide range of applications. The review focused on the use of plant-synthesized AgNPs in various biomedical applications as anti-microbial, anti-cancer, anti-inflammatory, and drug-delivery agents. The versatility and potential use of green AgNPs in the bio-medicinal sector provides an innovative alternative that can overcome the limitations of traditional systems. Thus proving green nanotechnology to be the future for medicine with continuous progress towards a healthier and safer environment by forming nanomaterials that are low- or non-toxic using a sustainable approach.

Bioactive components in Bambara groundnut (Vigna subterraenea (L.) Verdc) as a potential source of nutraceutical ingredients.

The utilization of nutraceuticals on a global scale has significantly increased over the past few years due to their reported health benefits and consumer's reluctance to consume synthetic drugs. This paper provides information regarding new and potential value added uses of biologically active compounds in Bambara groundnut (BGN) as ingredients that could be further researched and exploited for various applications. Nutraceutical is a food or part of food that apart from providing basic nutrients, offers medicinal benefits either by prevention and or treatment of an illness. BGN is a legume with rich nutrient profile that is under exploited industrially. It is widely used in African traditional medicine for its various health outcome, but has not been explored scientifically for its numerous nutraceutical potentials. Compared to beans BGN has greater quantity of soluble fiber and also have high dietary fiber. It is rich in polyphenolic compound which include flavonoids subgroups like flavonols, flavanols, anthocyanindins, isoflavones and phenolic acids: both benzoic acid and cinnamic acid derivatives, biologically active polyunsaturated fatty acids, proteins and peptides, antioxidant vitamins and minerals. The rising interest and emphasis in plant-based biologically active components (nutraceuticals) for various health promotion, has positioned this African legume as a potential source of nutraceutical ingredients (bioactive components) that could be exploited for improved nutrition and health.

Broad Spectrum Anti-Bacterial Activity and Non-Selective Toxicity of Gum Arabic Silver Nanoparticles.

Silver nanoparticles (AgNPs) are the most commercialized nanomaterials and presumed to be biocompatible based on the biological effects of the bulk material. However, their physico-chemical properties differ significantly to the bulk materials and are associated with unique biological properties. The study investigated the antimicrobial and cytotoxicity effects of AgNPs synthesized using gum arabic (GA), sodium borohydride (NaBH4), and their combination as reducing agents. The AgNPs were characterized using ultraviolet-visible spectrophotometry (UV-Vis), dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FT-IR). The anti-bacterial activity was assessed using agar well diffusion and microdilution assays, and the cytotoxicity effects on Caco-2, HT-29 and KMST-6 cells using MTT assay. The GA-synthesized AgNPs (GA-AgNPs) demonstrated higher bactericidal activity against all bacteria, and non-selective cytotoxicity towards normal and cancer cells. AgNPs reduced by NaBH4 (C-AgNPs) and the combination of GA and NaBH4 (GAC-AgNPs) had insignificant anti-bacterial activity and cytotoxicity at ≥50 µg/mL. The study showed that despite the notion that AgNPs are safe and biocompatible, their toxicity cannot be overruled and that their toxicity can be channeled by using biocompatible polymers, thereby providing a therapeutic window at concentrations that are least harmful to mammalian cells but toxic to bacteria.

Inhibitory potential of repurposed drugs against the SARS-CoV-2 main protease: a computational-aided approach.

The exponential increase in cases and mortality of coronavirus disease (COVID-19) has called for a need to develop drugs to treat this infection. Using in silico and molecular docking approaches, this study investigated the inhibitory effects of Pradimicin A, Lamivudine, Plerixafor and Lopinavir against SARS-CoV-2 Mpro. ADME/Tox of the ligands, pharmacophore hypothesis of the co-crystalized ligand and the receptor, and docking studies were carried out on different modules of Schrodinger (2019-4) Maestro v12.2. Among the ligands subjected to ADME/Tox by QikProp, Lamivudine demonstrated drug-like physico-chemical properties. A total of five pharmacophore binding sites (A3, A4, R9, R10, and R11) were predicted from the co-crystalized ligand and the binding cavity of the SARS-CoV-2 Mpro. The docking result showed that Lopinavir and Lamivudine bind with a higher affinity and lower free energy than the standard ligand having a glide score of -9.2 kcal/mol and -5.3 kcal/mol, respectively. Plerixafor and Pradimicin A have a glide score of -3.7 kcal/mol and -2.4 kcal/mol, respectively, which is lower than the co-crystallized ligand with a glide score of -5.3 kcal/mol. Molecular dynamics confirmed that the ligands maintained their interaction with the protein with lower RMSD fluctuations over the trajectory period of 100 nsecs and that GLU166 residue is pivotal for binding. On the whole, present study specifies the repurposing aptitude of these molecules as inhibitors of SARS-CoV-2 Mpro with higher binding scores and forms energetically stable complexes with Mpro.Communicated by Ramaswamy H. Sarma.

Bioinformatics Prediction and Analysis of MicroRNAs and Their Targets as Biomarkers for Prostate Cancer: A Preliminary Study.

Prostate cancer (PCa) is the second most common form of cancer in men around the world. Due to its heterogeneity, presentations range from aggressive lethal disease to indolent disease. There is a need to identify core biomarkers that are important for early detection and progression, allowing a more precise method for the treatment and management of Pca. We obtained metastatic prostate cancer associated microRNA array profiles from the GSE28029 dataset in the GEO database. MicroRNA target prediction was done using the databases, TargetScanHuman, miRDB and DIANA microT, six target genes (FOXC1, CDKN1A, BIRC2, CTNND1, ELK1 and LRP8) were found to be common among the three different databases. Differential expression of the target genes was performed via the GENT2 database in the GPL96 platform (HG-U133A). Results indicated all genes were downregulated. Gene Ontology (GO) was used to perform enrichment analysis. The GO enrichment analysis indicated that the downregulated genes were enriched in cellular response to gamma radiation, regulation of transcription and response to drugs as well as protein binding and receptor signaling protein activity. The study suggested that CDKN1A, FOXC1 and BIRC2 might be core genes for prostate cancer that play an important role in its diagnosis, development and progression.

Phenolic content, antioxidant, cytotoxic and antiproliferative effects of fractions of Vigna subterraenea (L.) verdc from Mpumalanga, South Africa.

Consistent intake of legumes has been correlated with decreased possibility of developing colorectal cancer (CRC) due to the content of some phytochemicals like polyphenols. Bambara groundnut (BGN) is an underutilized crop with a rich nutritional profile, but have not been exploited for its nutraceutical and medicinal benefits. In this study, total polyphenol, flavonoid (flavonol and flavanol) content, antioxidant activity and cytotoxicity/antiproliferative properties of 70% ethanolic extracts of whole BGN, cotyledon and seed coat on Caco-2 and HT-29 colon cancer cells were evaluated. Seed coat had a significantly (p < 0.05) higher composition of total polyphenol, flavonol and flavan-3-ol (flavanol) compared to whole seed and cotyledon. Antioxidant activity determined with ferric reducing antioxidant power (FRAP), 2,2- azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and oxygen radical absorbance capacity (ORAC) assays, showed that seed coat with higher polyphenolic content had significantly (p < 0.05) greater antioxidant activity. BGN fractions demonstrated cytotoxic and antiproliferative effects against HT-29 and Caco-2 colon cancer cells in a dose-dependent manner, with seed coat and whole seed exhibiting greater cytotoxicity and higher antiproliferative activity and colon cancer cell inhibition. Extracts of the cotyledon also showed cytotoxic activity and hindered cancer cell growth/division but to a significantly (p < 0.05) lower magnitude. BGN parts indicated a greater cytotoxic effect and potential to slow down Caco-2 colon cancer cell growth and division over HT-29. This result provides new knowledge on the possible health benefits of BGN, as well as the potential for product development and may influence its consumption and utilisation.

Multifunctional Gold Nanoparticles for Improved Diagnostic and Therapeutic Applications: A Review.

The medical properties of metals have been explored for centuries in traditional medicine for the treatment of infections and diseases and still practiced to date. Platinum-based drugs are the first class of metal-based drugs to be clinically used as anticancer agents following the approval of cisplatin by the United States Food and Drug Administration (FDA) over 40 years ago. Since then, more metals with health benefits have been approved for clinical trials. Interestingly, when these metals are reduced to metallic nanoparticles, they displayed unique and novel properties that were superior to their bulk counterparts. Gold nanoparticles (AuNPs) are among the FDA-approved metallic nanoparticles and have shown great promise in a variety of roles in medicine. They were used as drug delivery, photothermal (PT), contrast, therapeutic, radiosensitizing, and gene transfection agents. Their biomedical applications are reviewed herein, covering their potential use in disease diagnosis and therapy. Some of the AuNP-based systems that are approved for clinical trials are also discussed, as well as the potential health threats of AuNPs and some strategies that can be used to improve their biocompatibility. The reviewed studies offer proof of principle that AuNP-based systems could potentially be used alone or in combination with the conventional systems to improve their efficacy.

Citrate-capped gold nanoparticles with a diameter of 14 nm alter the expression of genes associated with stress response, cytoprotection and lipid metabolism in CaCo-2 cells.

Advancements in nanotechnology have provided insight into the unique opportunities for the application of nanomaterials such as gold nanoparticles (AuNPs) in medicine due to their remarkable properties, which includes low toxicity, large surface area, and the ease of synthesis and conjugation to other molecules. Therefore, AuNPs are often preferred for bio-applications. Citrate-capped AuNPs (cAuNPs) have been reported to be non-cytotoxic and are used in numerous studies as drug delivery vehicles to treat various diseases. However, the limitations of bioassays often used to assess the toxicity of AuNPs have been well documented. Herein, we investigate the cytotoxicity of 14 nm cAuNPs in the human colorectal adenocarcinoma (Caco-2) cell line. Treatment conditions (i.e. dose and exposure time) that were established to be non-toxic to Caco-2 cells were used to investigate the effect of cAuNPs on the expression of a Qiagen panel of 86 genes involved in cytotoxicity. Out of 86 studied, 23 genes were differentially expressed. Genes involved in oxidative stress and antioxidant response, endoplasmic reticulum (ER) stress and unfolded protein response, heat shock response, and lipid metabolism were more affected than others. While low concentrations of 14 nm cAuNPs was not cytotoxic and did not cause cell death, cells treated with these nanoparticles experienced ER and oxidative stress, resulting in the activation of cytoprotective cellular processes. Additionally, several genes involved in lipid metabolism were also affected. Therefore, 14 nm cAuNPs can safely be used as drug delivery vehicles at low doses.

Green Synthesis of Metallic Nanoparticles Using Some Selected Medicinal Plants from Southern Africa and Their Biological Applications.

The application of metallic nanoparticles (MNPs), especially that of silver, gold, cobalt, and zinc as antimicrobial, anticancer, drug delivery, contrast, and bioimaging agents has transformed the field of medicine. Their functions, which are attributed to their physicochemical properties, have gained prominence in various technological fields. Although MNPs can be produced via rigorous physical and chemical techniques, in recent years, a biological approach utilizing natural materials has been developed. With the increasing enthusiasm for safe and efficient nanomaterials, the biological method incorporating microorganisms and plants is preferred over physical and chemical methods of nanoparticle synthesis. Of these bio-entities, plants have received great attention owing to their capability to reduce and stabilize MNPs in a single one-pot protocol. South Africa is home to ~10% of the world's plant species, making it a major contributor to the world's ecological scenery. Despite the documented contribution of South African plants, particularly in herbal medicine, very few of these plants have been explored for the synthesis of the noble MNPs. This paper provides a review of some important South African medicinal plants that have been utilized for the synthesis of MNPs. The enhanced biological properties of the biogenic MNPs attest to their relevance in medicine. In this endeavour, more of the African plant biodiversity must be explored for the synthesis of MNPs and be validated for their potential to be translated into future nanomedicine.

Role of π-conjugation on the coordination behaviour, substitution kinetics, DNA/BSA interactions, and in vitro cytotoxicity of carboxamide palladium(II) complexes.

Treatments of N-(pyridin-2-ylmethyl)pyrazine-2-carboxamide (L1), N-(quinolin-8-yl)pyrazine-2-carboxamide (L2), N-(quinolin-8-yl)picolinamide (L3) and N-(quinolin-8-yl)quinoline-2-carboxamide (L4) with [PdCl2(NCMe)]2 afforded the corresponding Pd(ii) complexes, [Pd(L1)Cl] (PdL1); [Pd(L2)Cl] (PdL2); [Pd(L3)Cl] (PdL3); and [Pd(L4)Cl] (PdL4) in moderate yields. Structural characterisation of the compounds was achieved by NMR and FT-IR spectroscopies, elemental analyses and single crystal X-ray crystallography. The solid-state structures of complexes PdL2-PdL4 established the presence of one tridentate carboxamide and Cl ligands around the Pd(ii) coordination sphere, to give distorted square planar complexes. Electrochemical investigations of PdL1-PdL4 showed irreversible one-electron oxidation reactions. Kinetics reactivity of the complexes towards bio-molecules, thiourea (Tu), l-methionine (L-Met) and guanosine 5'-diphosphate disodium salt (5'-GMP) decreased in the order: PdL1 > PdL2 > PdL3 > PdL4, in tandem with the density functional theory (DFT) data. The complexes bind favourably to calf thymus (CT-DNA), and bovine serum albumin (BSA), and the order of their interactions agrees with the substitution kinetics trends. The in vitro cytotoxic activities of PdL1-PdL4 were examined in cancer cell lines A549, PC-3, HT-29, Caco-2, and HeLa, and a normal cell line, KMST-6. Overall, PdL1 and PdL3 displayed potent cytotoxic effects on A549, PC-3 HT-29 and Caco-2 comparable to cisplatin. All the investigated complexes exhibited lower toxicity on normal cells than cisplatin.

In vitroanti-oxidant and cytotoxic activities of gold nanoparticles synthesized from an aqueous extract of theXylopia aethiopicafruit.

The development of gold nanoparticles (AuNPs) using a green approach has drawn considerable interest in the field of nanomedicine. Its wide application in clinical diagnosis, imaging and therapeutics portrays its importance for human existence. In this study, we reported on the biogenic synthesis of AuNPs using the aqueous extract of theXylopia aethiopicafruit (AEXAf), which acts as both a reducing and stabilizing agent. The characterization of AEXAf-AuNPs was performed using ultraviolet-visible spectroscopy, dynamic light scattering and zeta potential measurements, high-resolution transmission electron microscopy and Fourier transform-infrared spectroscopy. Thein vitroanti-oxidant activities of the AEXAf-AuNPs and AEXAf were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing anti-oxidant power. Thein vitrocytotoxic activities of the AEXAf-AuNPs and AEXAf against breast and colorectal cancer cells were evaluated using 3,-(4,5 dimethylthiazol)-2,5 diphenyl tetrazolium bromide (MTT) viability and annexin V/PI assays. The AEXAf-AuNPs exhibited surface plasmon absorption maximum at 522 nm and were stable for 4 weeks. The average size of the AEXAf-AuNPs was 10.61 ± 3.33 nm on the high-resolution transmission electron microscopy images. Thein vitroanti-oxidant activities of the AEXAf-AuNPs and AEXAf were concentration dependent. The AEXAf-AuNPs were cytotoxic to the cancer cells and non-toxic to the non-cancerous human fibroblast cells (KMST-6) (up to 200µg ml-1). From these results, the AEXAf-AuNPs showed good anti-oxidant and anti-cancer activities, and can be suggested as a possible therapeutic agent for breast and colorectal cancer.