Eco-friendly green synthesis of AgNPs from Elaeocarpus serratus fruit extract: potential to antibacterial, antioxidant, cytotoxic effects of colon cancerous cells (HT-29) and its toxicity assessments of marine microcrustacean Artemia nauplii.

BACKGROUND: The present work demonstrated the green synthesis and characterization of silver nanoparticles (AgNPs) utilizing Elaeocarpus serratus fruit extract. The study examined the effectiveness of phytocompounds in fruit extract in reducing Ag+ to Ag° ions. METHODS: The water-soluble biobased substance production from silver ions to AgNPs in 45 min at room temperature. Surface plasmon resonance (SPR) peak was seen in the UV-visible absorption spectrum of the biologically altered response mixture. Examination with X-ray diffraction (XRD) showed that AgNPs are strong and have a face-centered cubic shape. Scanning electron microscope (SEM) investigation proved the production of AgNPs in a cuboidal shape. RESULTS: The AgNPs demonstrated remarkable antibacterial activity and a potent capacity to neutralize DPPH (2,2-Diphenyl-1-picrylhydrazyl) radicals. The highest growth inhibition was found for E. serratus against S. dysenteriae (18.5 ± 1.0 mm) and S. aureus (18 ± 1.2 mm). These nanoparticles exhibited robust antiradical efficacy even at low concentrations. The AgNPs additionally exhibited cytotoxic effects on (HT-29) human colon adenocarcinoma cancer cells. The MTT assay (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) indicated an inhibitory concentration (IC50) value of 49.1 ± 2.33 µg/mL for AgNPs, contrasting with the untreated cells of the negative control. The biotoxicity assessment using A. salina displayed mortality rates ranging from 8 to 69.33%, attributable to the E. serratus synthesized AgNPs. CONCLUSIONS: In our results concluded that simply first-hand information on that E. serattus fruit extract synthesized AgNPs were efficiently synthesized without the addition of any hazardous substances, and that they may be a strong antibacterial, antioxidant, and potential cytotoxic effects for the treatment of colon carcinoma cell lines.

The Graphene Quantum Dots Gated Nanoplatform for Photothermal-Enhanced Synergetic Tumor Therapy.

Currently, the obvious side effects of anti-tumor drugs, premature drug release, and low tumor penetration of nanoparticles have largely reduced the therapeutic effects of chemotherapy. A drug delivery vehicle (MCN-SS-GQDs) was designed innovatively. For this, the mesoporous carbon nanoparticles (MCN) with the capabilities of superior photothermal conversion efficiency and high loading efficiency were used as the skeleton structure, and graphene quantum dots (GQDs) were gated on the mesopores via disulfide bonds. The doxorubicin (DOX) was used to evaluate the pH-, GSH-, and NIR-responsive release performances of DOX/MCN-SS-GQDs. The disulfide bonds of MCN-SS-GQDs can be ruptured under high glutathione concentration in the tumor microenvironment, inducing the responsive release of DOX and the detachment of GQDs. The local temperature of a tumor increases significantly through the photothermal conversion of double carbon materials (MCN and GQDs) under near-infrared light irradiation. Local hyperthermia can promote tumor cell apoptosis, accelerate the release of drugs, and increase the sensitivity of tumor cells to chemotherapy, thus increasing treatment effect. At the same time, the detached GQDs can take advantage of their extremely small size (5-10 nm) to penetrate deeply into tumor tissues, solving the problem of low permeability of traditional nanoparticles. By utilizing the photothermal properties of GQDs, synergistic photothermal conversion between GQDs and MCN was realized for the purpose of synergistic photothermal treatment of superficial and deep tumor tissues.

Photoactivatable, mitochondria targeting dppz iridium(III) complex selectively interacts and damages mitochondrial DNA in cancer cells.

Cyclometalated Ir(III) complex [Ir(L)2(dppz)]PF6 (where L = 1-methyl-2-(thiophen-2-yl)-1H-benzo[d]imidazole and dppz = dipyrido [3,2-a:2',3'-c]phenazine) (Ir1) is potent anticancer agent whose potency can be significantly increased by irradiation with blue light. Structural features of the cyclometalated Ir(III) complex Ir1 investigated in this work, particularly the presence of dppz ligand possessing an extended planar area, suggest that this complex could interact with DNA. Here, we have shown that Ir1 accumulates predominantly in mitochondria of cancer cells where effectively and selectively binds mitochondrial (mt)DNA. Additionally, the results demonstrated that Ir1 effectively suppresses transcription of mitochondria-encoded genes, especially after irradiation, which may further affect mitochondrial (and thus also cellular) functions. The observation that Ir1 binds selectively to mtDNA implies that the mechanism of its biological activity in cancer cells may also be connected with its interaction and damage to mtDNA. Further investigations revealed that Ir1 tightly binds DNA in a cell-free environment, with sequence preference for GC over AT base pairs. Although the dppz ligand itself or as a ligand in structurally similar DNA-intercalating Ru polypyridine complexes based on dppz ligand intercalates into DNA, the DNA binding mode of Ir1 comprises surprisingly a groove binding rather than an intercalation. Also interestingly, after irradiation with visible (blue) light, Ir1 was capable of cleaving DNA, likely due to the production of superoxide anion radical. The results of this study show that mtDNA damage by Ir1 plays a significant role in its mechanism of antitumor efficacy. In addition, the results of this work are consistent with the hypothesis and support the view that targeting the mitochondrial genome is an effective strategy for anticancer (photo)therapy and that the class of photoactivatable dipyridophenazine Ir(III) compounds may represent prospective substances suitable for further testing.

Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening.

Background: DJ-1 is a ubiquitously expressed protein with multiple functions. Its overexpression has been associated with the occurrence of several cancers, positioning DJ-1 as a promising therapeutic target for cancer treatment. Methods: To find novel inhibitors of DJ-1, we employed a hybrid virtual screening strategy that combines structure-based and ligand-based virtual screening on a comprehensive compound library. Results: In silico study identified six hit compounds as potential DJ-1 inhibitors that were assessed in vitro at the cellular level. Compound 797780-71-3 exhibited antiproliferation activity in ACHN cells with an IC50 value of 12.18 µM and was able to inhibit the Wnt signaling pathway. This study discovers a novel covalent inhibitor for DJ-1 and paves the way for further optimization.

Synthesis, biological evaluation and docking studies of N-substituted resveratrol derivatives.

A total of 19 resveratrol derivatives, including 12 imines and 7 amines, were synthesized, among which compounds 1, 5, 6, 7', 11', and 13 are new compounds. The anti-inflammatory and antitumor activities of these compounds were evaluated in vitro. The results revealed that compounds 1, 6, 8', 12, and 12' exhibited significant inhibitory effects (> 50%) on NO production at the concentration of 10 µM and their NO production inhibitory activities have a significant concentration-dependent ability. Additionally, compounds 8' and 12' showed promising COX-2 inhibitory activity, and the molecular docking analysis indicated their stable binding to multiple amino acid residues within the active pocket of COX-2 through hydrogen bonding. Moreover, compound 12' exhibited inhibitory effects on various tumor cell lines and induced apoptosis in MCF-7 breast cancer cells, which was not observed with resveratrol alone. Therefore, the N-substituted structural modification of resveratrol would have possibly enhanced the bioactivity of resveratrol and facilitated its application.

Process optimization for green synthesis of silver nanoparticles using Rubus discolor leaves extract and its biological activities against multi-drug resistant bacteria and cancer cells.

Multi-drug resistant (MDR) bacteria are considered a serious public health threat. Also, increasing rate of resistance to anticancer drugs, as well as their toxicity, is another point of concern. Therefore, the new antibacterial and anticancer agents are always needed. The synthesizing silver nanoparticles (AgNPs) using medicinal plants, is an effective approach for developing novel antibacterial and anticancer agents. Rubus discolor, a native species of the Caucasus region, produces leaves that are typically discarded as a by-product of raspberry production. The present study has focused on optimizing the green synthesis of AgNPs using R. discolor leaves extract through response surface methodology. The optimal values for AgNPs synthesis were an AgNO3 concentration of 7.11 mM, a time of 17.83 h, a temperature of 56.51 °C, and an extract percentage of 29.22. The production of AgNPs was confirmed using UV-visible spectroscopy (λmax at 456.01 nm). TEM analysis revealed well-dispersed AgNPs (an average size of 37 nm). The XRD analysis confirmed the crystalline structure. The EDX detected a strong peak at 3 keV corresponded to Ag. The zeta potential value (- 44.2 mV) indicated the stability of nanoparticles. FT-IR spectra showed the presence of various functional groups from plant compounds, which play an important role in the capping and bio-reduction processes. The AgNPs revealed impressive antibacterial activities against MDR Escherichia coli and Pseudomonas aeruginosa (MIC ranging from 0.93 to 3.75 mg ml-1). The phytochemical analysis indicated the presence of phenolics, tannins, and flavonoids on the surface of AgNPs. They also showed significant cytotoxic effects on A431, MCF-7, and HepG2 cells (IC50 values ranging from 11 to 49.1 µg ml-l).

Exploring In-Silico, In-Vitro Antioxidant, and Cytotoxic Potential of Valerian wallichii by On Cervical Epithelial Carcinoma (HeLa) Cell Lines.

Traditional medicinal practices often utilize herbal remedies for treating various diseases. This study focuses on exploring the phytochemical constituents, in-silico, in-vitro antioxidant, and anticancer activities of Valerian wallichii root extracts on human cervical epithelial carcinoma (HeLa) cell lines. The molecular docking approach was employed to predict the ligand molecule's orientation within the receptor like Epidermal growth factor receptor tyrosine kinase domain (PDB ID: 1M17) using Schrodinger's GLIDE model. Among the selected phytocompounds, hesperidin exhibited promising inhibitory activity against EGFR (Epidermal Growth Factor Receptor) domain with -8.701 kcal/mol docking score and interactions with MET 769, ASP 831, ASP776, LEU694 and ASN818 residues as compared to standard doxorubicin with -7.6 kcal/mol docking score and interactions with ASP 831, ASN818 and ASP776 residues and further, various antioxidant activity was assessed and In-vitro anticancer activity against HeLa cell lines was evaluated by hydroalcoholic root extracts demonstrated antioxidant capacities, and selective cytotoxicity was observed, with IC50 : 45.759±0.42 µg/mL for the overall extract and IC50 : 30.245±0.58 µg/mL for the EAF fraction as compared to standard doxorubicin with IC50 : 25.9891±0.25 µg/mL, respectively. The present study concluded that Valerian wallichii L possesses potential human cervical epithelial carcinoma cell line inhibition properties based on the computer aided drug design models and in-vitro activity.

Synthesis, characterization of novel N-(4-cyano-1,3-oxazol-5-yl)sulfonamide derivatives and in†vitro screening their activity against NCI-60 cancer cell lines.

A novel series of N-(4-cyano-1,3-oxazol-5-yl)sulfonamides have been synthesized and characterized by IR, 1 H NMR, 13 C NMR spectroscopy, elemental analysis and chromato-mass-spectrometry. The anticancer activities of all newly synthesized compounds were evaluated via a single high-dose assay (10 µM) against 60 cancer cell lines by the National Cancer Institute (USA) according to its screening protocol. Among them, compounds 2 and 10 exhibited the highest activity against the 60 cancer cell lines panel in the one-dose assay. Compounds 2 and 10 showed inhibitory activity within the GI50 parameter and in five dose analyses. However, their cytostatic activity was only observed against some cancer cell lines, and cytotoxic concentration was outside the maximum used, i. e., >100 µM. The COMPARE analysis showed that the average graphs of the tested compounds have a moderate positive correlation with compounds with the L-cysteine analog and vinblastine (GI50 ) as well as paclitaxel (TGI), which target microtubules. Therefore, disruption of microtubule formation may be one of the mechanisms of the anticancer activity of the tested compounds, especially since among tubulin inhibitors with antitumor activity, compounds with an oxazole motif are widely represented. Therefore, N-(4-cyano-1,3-oxazol-5-yl)sulfonamides may be promising for further functionalization to obtain more active compounds.

Evaluation of antioxidant properties and cytotoxicity of brown algae (nizamuddinia zanardinii) in uterine (hela) and pancreatic cancer cell lines (paca-2).

INTRODUCTION: Pancreatic cancer and cervical cancer are among the most common cancers. Brown algae have anti-inflammatory, anti-cancer, anti-fungal, antioxidant, and immune-boosting properties. This study investigated the antioxidant properties and the effect of brown algae extract on pancreatic and uterine cancer cells. MATERIALS AND METHODS: In this study, Cervical (Hela) and pancreas (Paca-2) cancer cell lines were examined. The algae materials were extracted by sequential maceration method and amount of fucoxanthin content in the sample was determined by using High Performance Liquid Chromatography (HPLC) system. The cytotoxic effect of different concentrations of brown algae was measured by the MTT assay. All statistical calculations for comparing IC50 were analyzed using Graph Pad Prism software. RESULTS: the algal sample contained an average of 102.52 ± 0.12 µg of fucoxanthin per 100 g. IC50 for 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide free radical scavenging activity for methanolic extract was 2.02 and 11.98 ± 0.13 respectively. Brown algae in all fractions inhibited cell growth and survival. In Hela cell lines, the methanolic extract was the most effective inhibitor, while in Paca cell lines, hexane and methanolic extracts were particularly potent. The methanolic extract was more toxic than other fractions on Hela and Paca cell lines. CONCLUSION: This study highlights brown algae extracts strong anticancer effects on uterine and pancreatic cancer cells, suggesting its potential as a natural anticancer drug. Different fractions of the extract showed superior apoptotic and cytotoxic effects, with higher concentrations leading to increased apoptotic effects and reduced survival rates of cancer cells.

Flavonoid Myricetin as Potent Anticancer Agent: A Possibility towards Development of Potential Anticancer Nutraceuticals.

Good nutrition plays a crucial role in maintaining a balanced lifestyle. The beneficial effects of nutrition have been found to counteract nutritional disturbances with the expanded use of nutraceuticals to treat and manage cardiovascular diseases, cancer, and other developmental defects over the last decade. Flavonoids are found abundantly in plant-derived foods such as fruits, vegetables, tea, cocoa, and wine. Fruits and vegetables contain phytochemicals like flavonoids, phenolics, alkaloids, saponins, and terpenoids. Flavonoids can act as anti-inflammatory, anti-allergic, anti-microbial (antibacterial, antifungal, and antiviral) antioxidant, anti-cancer, and anti-diarrheal agents. Flavonoids are also reported to upregulate apoptotic activity in several cancers such as hepatic, pancreatic, breast, esophageal, and colon. Myricetin is a flavonol which is naturally present in fruits and vegetables and has shown possible nutraceutical value. Myricetin has been portrayed as a potent nutraceutical that may protect against cancer. The focus of the present review is to present an updated account of studies demonstrating the anticancer potential of myricetin and the molecular mechanisms involved therein. A better understanding of the molecular mechanism(s) underlying its anticancer activity would eventually help in its development as a novel anticancer nutraceutical having minimal side effects.

Cordia Dichotoma: A Comprehensive Review of its Phytoconstituents and Endophytic Fungal Metabolites and their Potential Anticancer Effects.

Cordia Dichotoma is a valuable medicinal plant belonging to the family Boraginaceae. It consists of several beneficial secondary metabolite components, including alkaloids, carbohydrates, flavonoids, glycosides, saponins, and tannins. Numerous studies have been conducted to assess the anticancer properties of Cordia Dichotoma on MCF-7, A-549, PC3, and HeLa cancer cell lines, primarily utilizing ethanolic extract, methanolic extract, and chloroform extract. The results of these studies have demonstrated significant effects. Furthermore, several studies have revealed the rich phytoconstituent content of Cordia Dichotoma with some significant components previously utilized by researchers to investigate the anticancer properties of specific compounds. This review discusses several of these components, including ß-sitosterol, α-amyrin, Quercitrin, Robinin, betulin, Taxifolin, and Hesperetin. Additionally, a recent study uncovered that the anticancer effect of metabolites from endophytic fungi residing on the Cordia Dichotoma plant is attributed to a property of the plant itself. This review focuses on the current state of anticancer research related to this plant and its components.

Cyclometalated Ir(III) theranostic molecular probe enabled mitochondria targeted fluorescence-SERS-guided phototherapy in breast cancer cells.

The increased energy demands inherent in cancer cells necessitate a dependence on mitochondrial assistance for their proliferation and metastatic activity. Herein, an innovative photo-medical approach has been attempted, specifically targeting mitochondria, the cellular powerhouses, to attain therapeutic benefit. This strategy facilitates the rapid and precise initiation of apoptosis, the programmed cell death process. In this goal, we have synthesized cyclometalated Iridium (III) molecular probes, denoted as Ir-CN and Ir-H, with a nitrile (CN) and a hydrogen-functionalized bipyridine as ancillary ligands, respectively. Ir-CN has shown superior photosensitizing properties and lower dark cytotoxicity compared to Ir-H in the breast cancer cell line MCF-7, positioning it as the preferred probe for photodynamic therapy (PDT). The synthesized Ir-CN induces alterations in mitochondrial membrane potential, disrupting the respiratory chain function, and generating reactive oxygen species that activate signaling pathways leading to cell death. The CN-conjugated bipyridine ligand in Ir-CN contributes to the intense red fluorescence and the positive charge on the central metal atom facilitates specific mitochondrial colocalization (colocalization coefficient of 0.90). Together with this, the Iridium metal, with strong spin-orbit coupling, efficiently generates singlet oxygen with a quantum yield of 0.79. Consequently, the cytotoxic singlet oxygen produced by Ir-CN upon laser exposure disrupts mitochondrial processes, arresting the electron transport chain and energy production, ultimately leading to programmed cell death. This mitochondrial imbalance and apoptotic induction were dually confirmed through various apoptotic assays including Annexin V staining and by mapping the molecular level changes through surface-enhanced Raman spectroscopy (SERS). Therefore, cyclometalated Ir-CN emerges as a promising molecular probe for cancer theranostics, inducing laser-assisted mitochondrial damage, as tracked through bimodal fluorescence and SERS.

Anti-breast cancer activity of biosynthesized selenium nanoparticles using Bacillus coagulans supernatant.

BACKGROUND: In the present study, Selenium Nanoparticles (SeNPs) were prepared using Bacillus coagulans, which is a type of Lactic Acid Bacteria (LAB), and then they were applied to treat breast cancer cells. METHODS: The chemicophysical properties of the bioengineered SeNPs were investigated by Transmission Electron Microscopy (TEM), Field Emission Scanning Electron Microscopy (FE-SEM), zeta potential, dynamic light scattering, Fourier Transform Infrared Spectroscopy (FT-IR), energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction analysis (XRD). The cytotoxic potential of SeNPs was evaluated by MTT assay against MCF-7 breast cancer cell line. The expression levels of apoptotic genes including BAX, BCL2, VEGF, ERBB2, CASP3, CASP9, CCNE1, CCND1, MMP2 and MMP9 were determined by real-time PCR. The rate of apoptosis and necrosis of the cancer cells as well as the results of the cell cycle were evaluated by flow cytometry method. RESULTS: The synthesized SeNPs had an average particle size of about 24-40 nm and a zeta potential of -16.1 mV, indicating the high stability of SeNPs. EDX results showed presence of SeNPs because amount of selenium in SeNPs was 86.6 % by weight. The cytotoxicity results showed a concentration-dependent effect against MCF-7 cells. The half-maximal inhibitory concentration (IC50) values of B. coagulans supernatant and SeNPs against breast cancer cells were 389.7 µg/mL and 17.56 µg/mL, respectively. In addition, SeNPs synthesized by the green process exhibited enhanced apoptotic potential in MCF-7 cancer cells compared with bacterial supernatants. Cancer cells treated with IC50 concentration of SeNPs induced 32 % apoptosis compared to untreated cells (3 % apoptosis). The gene expression levels of BAX, CASP3, and CASP9 were upregulated, while the expression levels of BCL2, CCNE1, CCND1, MMP2, MMP9, VEGF, and ERBB2 were downregulated after SeNPs treatment of cells. The potential of SeNPs to induce cell apoptosis was demonstrated by the increase in the expression level of BAX gene and the decrease in the expression level of BCL2 after treatment of cancer cells with SeNPs. CONCLUSION: The obtained results indicated that SeNPs had strong potential to induce significant cell apoptosis and are cytotoxic against the MCF-7 cancer cell line.

Ruthenium(II)-Arene Curcuminoid Complexes as Photosensitizer Agents for Antineoplastic and Antimicrobial Photodynamic Therapy: In Vitro and In Vivo Insights.

Photodynamic therapy (PDT) is an anticancer/antibacterial strategy in which photosensitizers (PSs), light, and molecular oxygen generate reactive oxygen species and induce cell death. PDT presents greater selectivity towards tumor cells than conventional chemotherapy; however, PSs have limitations that have prompted the search for new molecules featuring more favorable chemical-physical characteristics. Curcumin and its derivatives have been used in PDT. However, low water solubility, rapid metabolism, interference with other drugs, and low stability limit curcumin use. Chemical modifications have been proposed to improve curcumin activity, and metal-based PSs, especially ruthenium(II) complexes, have attracted considerable attention. This study aimed to characterize six Ru(II)-arene curcuminoids for anticancer and/or antibacterial PDT. The hydrophilicity, photodegradation rates, and singlet oxygen generation of the compounds were evaluated. The photodynamic effects on human colorectal cancer cell lines were also assessed, along with the ability of the compounds to induce ROS production, apoptotic, necrotic, and/or autophagic cell death. Overall, our encouraging results indicate that the Ru(II)-arene curcuminoid derivatives are worthy of further investigation and could represent an interesting option for cancer PDT. Additionally, the lack of significant in vivo toxicity on the larvae of Galleria mellonella is an important finding. Finally, the photoantimicrobial activity of HCurc I against Gram-positive bacteria is indeed promising.

Identification of Bulbocodin D and C as novel STAT3 inhibitors and their anticancer activities in lung cancer cells.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC50s for BD and BC were 11.63 and 11.71 µmol·L-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.

Co-encapsulation of hydrophilic and hydrophobic drugs into niosomal nanocarrier for enhanced breast cancer therapy: In silico and in vitro studies.

Combination therapy has been considered one of the most promising approaches for improving the therapeutic effects of anticancer drugs. This is the first study that uses two different antioxidants in full-characterized niosomal formulation and thoroughly evaluates their synergistic effects on breast cancer cells. In this study, in-silico studies of hydrophilic and hydrophobic drugs (ascorbic acid: Asc and curcumin: Cur) interactions and release were investigated and validated by a set of in vitro experiments to reveal the significant improvement in breast cancer therapy using a co-delivery approach by niosomal nanocarrier. The niosomal nanoparticles containing surfactants (Span 60 and Tween 60) and cholesterol at 2:1 M ratio were prepared through the film hydration method. A systematic evaluation of nanoniosomes was carried out. The release profile demonstrated two phases (initial burst followed by sustained release) and a pH-dependent release schedule over 72 h. The optimized niosomal preparation displayed superior storage stability for up to 2 months at 4 °C, exhibiting extremely minor changes in pharmaceutical encapsulation efficiency and size. Free dual drugs (Asc + Cur) and dual-drug loaded niosomes (Niosomal (Asc + Cur)) enhanced the apoptotic activity and cytotoxicity and inhibited cell migration which confirmed the synergistic effect of co-encapsulated drugs. Also, significant up-regulation of p53 and Bax genes was observed in cells treated with Asc + Cur and Niosomal (Asc + Cur), while the anti-apoptotic Bcl-2 gene was down-regulated. These results were in correlation with the increase in the enzyme activity of SOD, CAT, and caspase, and the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) upon treatment with the mentioned drugs. Furthermore, these anti-cancer effects were higher when using Niosomal (Asc + Cur) than Asc + Cur. Histopathological examination also revealed that Niosomal (Asc + Cur) had a lower mitosis index, invasion, and pleomorphism than Asc + Cur. These findings indicated that niosomal formulation for co-delivery of Asc and Cur would offer a promising delivery system for an effective breast cancer treatment.

Antimicrobial, Antibiofilm, and Anticancer Activities of Syzygium aromaticum Essential Oil Nanoemulsion.

In the current study, clove oil nanoemulsion (CL-nanoemulsion) and emulsion (CL-emulsion) were prepared through an ecofriendly method. The prepared CL-nanoemulsion and CL-emulsion were characterized using dynamic light scattering (DLS) and a transmission electron microscope (TEM), where results illustrated that CL-nanoemulsion droplets were approximately 32.67 nm in size and spherical in shape, while CL-nanoemulsion droplets were approximately 225.8 nm with a spherical shape. The antibacterial activity of CL-nanoemulsion and CL-emulsion was carried out using a microbroth dilution method. Results revealed that the preferred CL-nanoemulsion had minimal MIC values between 0.31 and 5 mg/mL. The antibiofilm efficacy of CL-nanoemulsion against S. aureus significantly decreased the development of biofilm compared with CL-emulsion. Furthermore, results illustrated that CL-nanoemulsion showed antifungal activity significantly higher than CL-emulsion. Moreover, the prepared CL-nanoemulsion exhibited outstanding antifungal efficiency toward Candida albicans, Cryptococcus neoformans, Aspergillus brasiliensis, A. flavus, and A. fumigatus where MICs were 12.5, 3.12, 0.78, 1.56, and 1.56 mg/mL, respectively. Additionally, the prepared CL-nanoemulsion was analyzed for its antineoplastic effects through a modified MTT assay for evaluating apoptotic and cytotoxic effects using HepG2 and MCF-7 cell lines. MCF-7 breast cancer cells showed the lowest IC50 values (3.4-fold) in CL-nanoemulsion relative to that of CL-emulsion. Thus, CL-nanoemulsion induces apoptosis in breast cancer cells by inducing caspase-8 and -9 activity and suppressing VEGFR-2. In conclusion, the prepared CL-nanoemulsion had antibacterial, antifungal, and antibiofilm as well as anticancer properties, which can be used in different biomedical applications after extensive studies in vivo.

Resveratrol-Loaded Attalea funifera Oil Organogel Nanoparticles: A Potential Nanocarrier against A375 Human Melanoma Cells.

This study aimed to evaluate Attalea funifera seed oil with or without resveratrol entrapped in organogel nanoparticles in vitro against A375 human melanoma tumor cells. Organogel nanoparticles with seed oil (SON) or with resveratrol entrapped in the seed oil (RSON) formed functional organogel nanoparticles that showed a particle size <100 nm, polydispersity index <0.3, negative zeta potential, and maintenance of electrical conductivity. The resveratrol entrapment efficiency in RSON was 99 ± 1%. The seed oil and SON showed no cytotoxicity against human non-tumor cells or tumor cells. Resveratrol at 50 µg/mL was cytotoxic for non-tumor cells, and was cytotoxic for tumor cells at 25 µg/mL. Resveratrol entrapped in RSON showed a decrease in cytotoxicity against non-tumor cells and cytotoxic against tumor cells at 50 µg/mL. Thus, SON is a potential new platform for the delivery of resveratrol with selective cytotoxic activity in the treatment of melanoma.

Anticancer activity of Ni(II) and Zn(II) complexes based on new unsymmetrical salophen-type ligands: synthesis, characterization and single-crystal X-ray diffraction.

The discovery of new coordination compounds with anticancer properties is an active field of research due to the severe side effects of platinum-based compounds currently used in chemotherapy. In the search for new agents for the treatment of cancer, unsymmetrical N2O2-tetradentate ligand (H2L1 and H2L2) and their Ni(II) and Zn(II) asymmetric complexes (NiII-L1-2 and ZnII-L1-2) have been synthesized and fully characterized. 1H NMR studies revealed that the ligands and complexes were stable in mixtures of DMSO : D2O (9 : 1). Complementary UV-Vis studies confirmed that ZnII derivatives also exhibit high stability in mixtures DMSO : buffer (6 : 4) after 24 h. Single-crystal X-ray diffraction studies confirmed the molecular structures of H2L1, H2L2, NiII-L1, and NiII-L2. At the molecular level, complexes were completely planar without significant distortions of the square-planar geometry according to τ4 parameter. Furthermore, the crystalline structures revealed non-classical intermolecular interactions of the C-H⋯O and the Ni⋯Ni type. The ligands and complexes were screened against the human osteosarcoma (MG-63), human colon cancer (HCT-116), breast cancer (MDA-MB-231) cell lines, and non-cancerous cells (L929). H2L1 and H2L2 ligands not caused cytotoxic effects at a concentration of 100 µM, while NiII-L2, ZnII-L1, and ZnII-L2 complexes induce cytotoxic effects in all cell lines. NiII-L2 was a more active complex against MG-63 (3.9 ± 1.5) and HCT-116 (3.4 ± 1.7) cell lines with IC50 values in the low micromolar range. In addition, this compound was 10-, 5-, and 11-fold more potent than cisplatin in MG-63 (39 ± 1.8), HCT-116 (17.2), and MDA-MB-231 (131 ± 18), respectively. Three complexes exhibited great selectivity for tumoral cells with SI values ranging from 1.6 to 7.4.

Synthesis, antioxidant, antiproliferative activity, molecular docking and DFT studies of novel isoxazole derivatives of diosgenin, a steroidal sapogenin from Dioscorea deltoidea.

Diosgenin [25R-spirost-5-en-3ß-ol], isolated from Dioscorea deltoidea was used as a starting material for synthesizing its various isoxazole derivatives. A library of fifteen isoxazole analogues (DG1-DG15) were synthesised via modification at the C-3 hydroxyl group. The resulting analogues were fully characterized by spectral techniques and evaluated for their antioxidant and anticancer activity against four breast cancer cell lines; MDA-MB-231, MDA-MB-468, MCF-7, and 4 T1, using MTT assay. Molecular docking studies were carried out for all analogues with EGFR protein (PDB id: 6LUD) to check their activity by inhibiting EGFR protein, which is an effective strategy for cancer cell death. Furthermore, DFT studies were carried out for four analogues. Among all analogues, compound DG6 and DG9 showed the highest scavenging activity and compound DG9 exhibited a maximum cytotoxic effect on the MDA-MB-468 and MCF-7 cell lines with an IC50 value of 6.25 µg/mL and 6.81 µg/mL, while compound DG5 was the least potent (IC50 25.89 µg/mL). Molecular docking results revealed that DG8 and DG9 afforded the highest binding energy of -14.33 and - 14.71 kcal/mol, respectively for the target EGFR protein. These results demonstrate the potential of diosgenin analogues as drug candidates for breast cancer therapy. Furthermore, DFT studies revealed that the molecules are more polarizable and have smaller energy gap between their HOMO and LUMO orbitals, the smallest being of DG9 (3.221 eV) and hence are more reactive.