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Lens culinaris L., has been widely recognized for its medical applications. LC-ESI-TOF-MS identified 22 secondary metabolites including phenolics, flavonoids, and anthocyanidin glycosides among its total extract (LCTE). The study aimed to apply LCTE as a biogenic material for reducing and capping the silver nanoparticles (LC-AgNPs). The ynthesized LC-AgNPs were characterized using different techniques. The UV absorption was observed at λmax 379 nm. LC-AgNPs were spherical, with 19.22 nm average size. The face cubic centre nature was demonstrated by HR-TEM and XRD. The LC-AgNPs were then evaluated for their anticancer and antimicrobial potentials. LC-AgNPs showed an extremely potent cytotoxic activity against MCF-7, HCT-116 and HepG2 cell lines (IC50= 0.37, 0.35 and 0.1 µg/mL, respectively). LC-AgNPs induced significant apoptotic effects in the three examined cancer cell lines. LC-AgNPs resulted in sequestration of cells in G1 phase of the cell cycle in both MCF-7 and HCT-116 cells, meanwhile it trapped cells at the G2 phase in HepG2 cells. Moreover, the antimicrobial activity of LC-AgNPs was highly confirmed against Klebsiella pneumoniae and Acinetobacter baumannii. Molecular docking study designated Kaempferol-3-O-robinoside-7-O-rhamnoside and Quercetin-3-D-xyloside as the topmost LCTE active constituents that caused inhibition of both Bcl-2 and IspC cancer targets in combination with the produced silver nanoparticles.

This study uses the aerial parts of Panicum maximum total extract (PMTE) to synthesize silver nanoparticles (AgNPs) in an environmentally friendly manner. TEM, SEM, FTIR, X-ray powder diffraction (XRD), Zeta potential, UV, and FTIR were used to characterize the green silver nanoparticles (PM-AgNPs). PM-AgNPs were evaluated as anticancer agents compared to (PMTE) against breast (MCF-7), lung (A549), and ovary adenocarcinoma (SKOV3) human tumour cells. The antibacterial activity of AgNPs was assessed against Staphylococcus aureus isolates. The PM-AgNPs had an absorbance of 418 nm, particle size of 15.18 nm, and zeta potential of −22.4 mV, ensuring the nanosilver’s stability. XRD evaluated the crystallography nature of the formed PM-AgNPs. The cytotoxic properties of PM-AgNPs on MCF-7 and SKOV 3 were the strongest, with IC50s of 0.13 ± 0.015 and 3.5 ± 0.5 g/ml, respectively, as compared to A549 (13 ± 3.2 µg/mL). The increase in the apoptotic cells was 97.79 ± 1.61 and 96.6 ± 1.91% for MCF-7 and SKOV3 cell lines, respectively. PM-AgNPs were found to affect the membrane integrity and membrane permeability of 50 and 43.75% of the tested isolates, respectively. Also, PM-AgNPs have recorded a reduction in the biofilm formation of S. aurues. These results suggest using PM-AgNPs to treat breast and ovarian cancers.

Abstract Background α-Mangostin is a major xanthone in Garcinia mangostana L. (Clusiaceae) pericarps. It has promising anti-proliferative potential in different cancer cells; however, it has poor oral bioavailability. Phytosomes are used as a novel nano-based drug delivery system. The aim of this research was to enhance the anti-proliferative potency of α-mangostin by formulating it as α-mangostin-phytosome (α-M-PTMs) and assessing its impact on SKOV-3 ovarian cancer cells in comparison to pure α-mangostin. Results The size and entrapment efficiency of the proposed formulation were optimized using Box–Behnken statistics. The optimized formula was characterized using transmission electron microscope. The binding of α-mangostin to phospholipids was confirmed using Fourier-transform infrared (FTIR) spectroscopy. The optimized α-mangostin-phytosomes formula exhibited enhanced anti-proliferative activity with reference to raw α-mangostin. This was further substantiated by assessing the cell cycle phases that indicated an accumulation of SKOV-3 cells in the sub-G1 phase. Annexin-V staining revealed enhanced apoptotic activity in α-mangostin-phytosome-treated cells. This was associated with upregulation of CASP3 (Caspase-3), BAX (BCL2 Associated X, Apoptosis Regulator) and TP53 as well as down-regulation of BCL2 mRNA (B-Cell Leukemia/Lymphoma 2). Moreover, our data indicated enhanced ROS (Reactive oxygen species) production, cytochrome-C release, and disturbed MMP (mitochondrial membrane potential). Conclusion Encapsulation of α-mangostin in a phytosome nano-formula enhances its anti-proliferative effects in SKOV-3 cells via, at least in part, inducing mitochondrial apoptotic cell death.

The present study used Piper betle petiole leaf extract as an efficient reducing agent to produce zinc oxide nanoparticles (ZnO NPs). The change in the color of reaction mixture from brown to white indicates the formation of ZnO NPs, which is also noticed in UV–Visible spectral analysis (peak at 320 nm). Investigations using X-ray diffraction (XRD) revealed that the particles were crystalline. Additionally, scanning electron microscopy (SEM), Energy Dispersive X-ray diffraction (EDAX), dynamic light scattering (DLS), and Fourier transform infrared (FTIR) techniques were used to understand the structural, and elemental aspects of the as-prepared ZnO NPs. The antibacterial activity of ZnO NPs was assessed using the disc diffusion approach method against clinical strains of Escherichia coli, Pseudomonas fluorescence, Micrococcus luteus, and Bacillus subtilis. The zone of inhibition and minimum inhibitory indices (MIC) were used in this process. The as-prepared ZnO NPs showed strong antibacterial effects. In addition, the anticancer efficacy of the material was tested against MDA-MB-231 breast cancer cell lines, the results of which revealed that the tested ZnO NPs was potent in inhibiting the growth of the cancer cells. The mechanistic evaluation of such an activity carried out using in silico methods suggested that the anti-breast cancer activity of L-ZnONPs was mediated by human HER2 kinase domain. This suggests that preparation of ZnO NPs from plant sources can be an excellent method of producing biomedical goods that are both environmentally friendly and versatile.

The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.

Papain, as potential therapeutic regime, can be utilized for managing specific diseased conditions. However, its application has been limited due to its natural instability; especially when exposed to an acidic environment with a pH lower than 2.8. Therefore, the purpose of this study is to develop a Papain-loaded Nanostructured Lipid Carriers (Papain-NLC) using the Box-Behnken design (BBD) to explore the influence of different variables on the response. In this study, an optimized model was formulated based on predicted responses and the actual results closely aligned with the predicted values. Scanning Electron Microscope (SEM) and Fourier-transform infrared spectroscopy (FT-IR) were used to analyze particle size, shape, entrapment efficiency, and drug release in order to learn more about the interactions between the formulation’s components. In vitro release studies were performed, revealing a slow release of papain from the lipid matrix, coupled with the gradual degradation of matrix. Mathematical release kinetics, specifically the first-order kinetics model effectively described this release behaviour. In vitro bioaccessibility of Papain-NLCs using static digestion model was done and samples were evaluated by LC-MS/MS analysis. The results demonstrated that the static digestion model improved the bioaccessibility of Papain-NLCs. To ensure the chemical stability of Papain-NLCs, a six-month stability study was conducted, assessing particle size, polydispersity index, zeta potential and entrapment efficiency. Remarkably, no significant changes were observed, indicating the formulations robustness and potential for practical applications. Safety evaluation of the Papain-NLC’s were performed using CaCo2 cell lines, employing MTT assay for cell viability and LDH assay for cell toxicity assessment.

Chromobacterium violaceum an opportunistic human pathogenic bacterium, exhibits resistance to conventional antibiotics by exploiting its quorum sensing mechanism to regulate virulence factor expression. In light of this, disrupting the quorum sensing mechanism presents a promising avenue for treating infections caused by this pathogen. The study focused on using the cytoplasmic quorum sensing receptor CviR from C. violaceum as a model target to identify novel quorum sensing inhibitors from P. quassioides through in silico computational approaches. Molecular docking analyses unveiled that several phytochemicals derived from Picrasma quassioides exhibit the potential to inhibit quorum sensing by binding to CviR protein. Notably, the compounds such as Quassidine I (– 8.8 kcal/mol), Quassidine J (– 8.8 kcal/mol), Kumudine B (– 9.1 kcal/mol) and Picrasamide A (– 8.9 kcal/mol) exhibited high docking scores, indicating strong binding affinity to the CviR protein. The native ligand C6-HSL (N-hexanoyl-L-homoserine lactone) as a positive control/co-crystal inhibitor also demonstrated a significant binding energy of—7.7 kcal/mol. The molecular dynamics simulation for 200 ns showed the thermodynamic stability and binding affinity refinement of the top-ranked CviR inhibitor (Kumudine B) with its stable binding and minor fluctuations compared to positive control (C6-HSL). Pharmacokinetic predictions indicated that Kumudine B possesses favourable drug-like properties, which suggest its potential as a drug candidate. The study highlight Kumudine B as a potential agent for inhibiting the CviR protein in C. violaceum. The comprehensive evaluation of Kumudine B provides valuable insights into its pharmacological profiles, facilitating its assessment for diverse therapeutic applications and guiding future research activities, particularly as antibacterial agents for clinical drug development.

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Senescence is a complicated, multi-factorial, irreversible cell cycle halt that has a tumor-suppressing effect in addition to being a significant factor in aging and neurological diseases. Damaged DNA, neuroinflammation, oxidative stress and disrupted proteostasis are a few of the factors that cause senescence. Senescence is triggered by DNA damage which initiates DNA damage response. The DNA damage response, which includes the formation of DNA damage foci containing activated H2AX, which is a key factor in cellular senescence, is provoked by a double strand DNA break. Oxidative stress impairs cognition, inhibits neurogenesis, and has an accelerated aging effect. Senescent cells generate pro-inflammatory mediators known as senescence-associated secretory phenotype (SASP). These pro-inflammatory cytokines and chemokines have an impact on neuroinflammation, neuronal death, and cell proliferation. While it is tempting to think of neurodegenerative diseases as manifestations of accelerated aging and senescence, this review will present information on brain ageing and neurodegeneration as a result of senescence and DNA damage response.

In the rapidly expanding field of nanoscience and research, AgNPs and their diverse by-products have been acknowledged as having a green approach. Fruit extract of Limonia acidissima L. is capable of bio-reducing AgNO3 and stabilizing AgNPs. AgNPs distinctive absorption peak at 417 nm at pH 8 was visible on the UV-Vis spectrophotometer. The fruit extract contained bioactive chemicals, which may be the cause of the AgNPs bio-capping and stabilizing properties, according to Fourier transform infrared (FT-IR) spectroscopy. Using an X-ray diffractometer (XRD) examination, the AgNPs solid crystalline nature and size of 29.05 nm were investigated. Lastly, AFM and HR-TEM studies verified the AgNPs surface morphology, particularly their size and form. The DPPH assay method was used to measure the AgNPs capacity for radical scavenging. As compared to normal ascorbic acid and fruit extract (control), the AgNPs produced from the fruit extract demonstrated good antioxidant effectiveness. To evaluate the antibacterial activity of the AgNPs sample, it was additionally evaluated against E. coli, S. typhi, V. cholera, and S. aureus. With the greatest zone of inhibition and thus the strongest antibacterial activity, S. aureus (12.03 ± 0.043 mm) was the organism that displayed it. On the other hand, the least active strain was V. cholera (9.09 ± 0.013 mm). The data indicates that bio-fabricated silver nanoparticles (AgNPs) exhibited dose-dependent inhibitory efficacy together with a notable zone of inhibition. Additionally, S. aureus was shown to be more effective than V. cholera. Future health and pharmaceutical fields may benefit from the biocompatible method of separating AgNPs from L. acidissima fruit extract.

Manganese dioxide nanoparticles (MnO2 NPs) were synthesized via a typical green synthesis method involving Tridax procumbens (TP) leaf extract extraction and utilization. The as-prepared material was further characterized using various physio-chemical methods to comprehend its structural, morphological, and optical properties. Powder X-ray diffraction (PXRD) reveals a tetragonal system with a space group of I 41/a m d, clearly indicating the presence of phytochemicals (impurity peaks at 25.46° and 54.92° diffraction angles). The calculated crystalline size of the sample was found to be 43 nm. Field Emission Scanning Electron Microscope (FESEM) results confirm the precursors of the as-prepared sample, also revealing the agglomerated structure. Furthermore, deeper morphology and crystallinity of the as-prepared MnO2 NPs have been studied through High-Resolution Transmission Electron Microscope (HR-TEM) images, which affirms the information about calculated d-spacing value (0.328 nm) and confirming crystallinity through Selected Area Electron Diffraction (SAED) image. Absorption studies were conducted on as-prepared samples, which show a characteristic band at 257 nm, affirming the formation of MnO2 NPs. The same was utilized to evaluate the band gap energy (4.46 eV) through the Kubelka-Munk function. To further confirm the calculated particle size and stability of the as-prepared MnO2 NPs, Dynamic Light Scattering (DLS) analysis was conducted, and the results revealed that the particles’ size was 58.72 nm. The prepared samples were subjected to study antimicrobial studies against gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacterial species. The inhibition zone of the antibacterial disc soaked with as-prepared MnO2 NPs showed a significant increase compared to the TP leaf extract and commercially available MnO2 NPs. Also, the degradation of the Titan Yellow dye solution was conducted employing UV irradiation, and it was found that the maximum degradation percentage was attained after 120 min of irradiation. Furthermore, the pH effect on %degradation and reusability test were also conducted. The obtained results showed a pinnacle pH point of 4 where the degradation was maximum and found a decent decrement in %degradation after 4th usage. All the acquired results were utilized to study the degradation reaction kinetics, which was found that the present degradation holds good for both 0th and 1st order kinetic equations. Henceforth, the acquired results suggest that the green synthesized MnO2 NPs are potent candidates for antimicrobial and degrading activities.

Abstract Background Viscum orientale is a largely used parasitic plant with traditional medicinal properties. They are considered to possess the medicinal properties of host tree which they grow on. It’s a least explored plant with ethanopharmacological importance. As a result, the current work aimed to investigate the biological effects of Viscum orientale extract and silver nanoparticles (AgNPs) generated from it. Methods AgNPs synthesized using Viscum orientale plant extract and analysed on time dependent series and was characterized using Ultra Violet UV–visible spectra, Fourier Transform Infrared Spectroscopy FTIR, X-ray diffraction (XRD), Energy Dispersive X-ray Spectroscopy (EDX), Scanning Electron Microscopy (SEM). Further using disc method anti-microbial assay was performed following antioxidation screening using 1,1-diphenyl-2-picryl-hydrazyl (DPPH), reducing power and nitric oxide content and heamgglutination with human blood. Results On green synthesis using silver, the phyto contituents of plant Viscum orientale effectively reduced silver ions at 3-4 h of continuous stirring to form AgNPs. UV–vis spectra showed a typical peak of AgNPs at 480 nm. The FTIR analysis confirmed the covering of silver layers to bio-compounds of the extract. SEM analysis represented AgNPs as spherical morphologies ranging from 119–222 nm. AgNPs exhibited impressive zone of inhibition against Escherichia coli (8.1 ± 0.3 mm), Staphylococcus aureus (10.3 ± 0.3 mm), Bacillus subtilis (7.3 ± 0.3 mm), Bacillus cereus (8.2 ± 0.3 mm), Salmonella typhi (7.1 ± 0.2 mm). AgNps exhibited efficiency against DPPH at EC50 value of 57.60 µg/ml. and reducing power at EC50 of 53.42 µg/ml and nitric oxide scavenging of EC50 of 56.01 µg/ml concentration. Further, anthelmintic activity results showed synthesized nanoparticles significant reduction in the paralysis time to 5.4 ± 0.3 min and death time to 6.5 ± 0.6 min in contrast to the individual factors. On hemagglutination using AgNPs, above 80 µg/ml of concentration showed very significant effect on comparison with water extract. Conclusion Synthesized AgNPs using Viscum orientale water extract displayed versatile biological activity than individual extract. This study has forecasted a new path to explore more on this AgNPs for further research.

Abstract Background The yellow jasmine flower (Jasminum humile L.) is a fragrant plant belonging to the Oleaceae family with promising phytoconstituents and interesting medicinal uses. The purpose of this study was to characterize the plant metabolome to identify the potential bioactive agents with cytotoxic effects and the underlying mechanism of cytotoxic activity. Methods First, HPLC–PDA-MS/MS was used to identify the potential bioactive compounds in the flowers. Furthermore, we assessed the cytotoxic activity of the flower extract against breast cancer (MCF-7) cell line using MTT assay followed by the cell cycle, DNA-flow cytometry, and Annexin V-FITC analyses alongside the effect on reactive oxygen species (ROS). Finally, Network pharmacology followed by a molecular docking study was performed to predict the pathways involved in anti-breast cancer activity. Results HPLC–PDA-MS/MS tentatively identified 33 compounds, mainly secoiridoids. J. humile extract showed a cytotoxic effect on MCF-7 breast cancer cell line with IC50 value of 9.3 ± 1.2 µg/mL. Studying the apoptotic effect of J. humile extract revealed that it disrupts G2/M phase in the cell cycle, increases the percentage of early and late apoptosis in Annexin V-FTIC, and affects the oxidative stress markers (CAT, SOD, and GSH-R). Network analysis revealed that out of 33 compounds, 24 displayed interaction with 52 human target genes. Relationship between compounds, target genes, and pathways revealed that J. humile exerts its effect on breast cancer by altering, Estrogen signaling pathway, HER2, and EGFR overexpression. To further verify the results of network pharmacology, molecular docking was performed with the five key compounds and the topmost target, EGFR. The results of molecular docking were consistent with those of network pharmacology. Conclusion Our findings suggest that J. humile suppresses breast cancer proliferation and induces cell cycle arrest and apoptosis partly by EGFR signaling pathway, highlighting J. humile as a potential therapeutic candidate against breast cancer.

Itraconazole (ITZ) is a renowned antifungal medication, however its therapeutic efficacy is limited by low solubility and oral bioavailability. The current research work attempted to augment the oral bioavailability of ITZ by incorporating into self-emulsifying micelles (SEMCs). To fabricate the SEMCs, various preparation techniques including physical mixture, melt-emulsification, solvent evaporation and kneading, were opted by using different weight ratio of drug and solubilizers i.e. Gelucire-50/13 or Gelucire-44/14 and characterized both in vitro and in vivo. The prepared SEMCs were found to be in the size range from 63.4 ± 5.2 to 284.2 ± 19.5 nm with surface charges ranging from −16 ± 1.2 to −27 ± 2.0 mV. The drug solubility was improved to a reasonable extent with all investigated formulations, however, SEMCs in group 6 prepared by kneading method (KMG6) using Gelucire-44/14: drug (10:1 presented 87.6 folds’ increase (964.93 ± 2 μg/mL) compared to solubility of crystalline ITZ (11 ± 2 μg/mL) through kneading method. In addition, KMG6 SEMCs shows the fast drug release compared to other SEMCs. Further, KMG6 SEMCs also exhibited 5.12-fold higher relative intestinal serosal fluid absorption compared to crystalline ITZ. The pharmacokinetic parameters such Cmax, AUC and Tmax of KMG6 SEMCs significantly improved compared to crystalline ITZ. In conclusion, the manipulation of ITZ solubility, dissolution rate and absorption using SEMCs is a promising strategy for bioavailability enhancement.

Abstract Cladosporium spp. have been reported for their great diversity of secondary metabolites which represent as a prominent base material for verifying the biological activities. Several bioactive compounds which have antimicrobial, cytotoxic, quorum sensing inhibitory and phytotoxic activities have been isolated from Cladosporium species. Most of them are still needed to be explored for their anticancer properties. Therefore, the present study is focused on screening and identifying the bioactive compounds of Cladosporium spp. for their anticancer activity via the integrated approaches of Molecular Docking (MD), Molecular Dynamics Simulation (MDS) and Density Functional Theory (DFT) studies. A total of 123 bioactive compounds of Cladosporium spp. were explored for their binding affinity with the selected breast cancer drug target receptor such as estrogen receptor alpha (PDB:6CBZ). The Molecular Docking studies revealed that amongst the bioactive compounds screened, Altertoxin X and Cladosporol H showed a good binding affinity of − 10.5 kcal/mol and − 10.3 kcal/mol, respectively, with the estrogen receptor alpha when compared to the reference compound (17 $$\upbeta$$ β -Estradiol: − 10.2 kcal/mol). The MDS study indicated the stable binding patterns and conformation of the estrogen receptor alpha-Altertoxin X complex in a stimulating environment. In addition, in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) study suggested that Altertoxin X has a good oral bioavailability with a high LD $$_{50}$$ 50 value of 2.375 mol/kg and did not cause any hepatotoxicity and skin sensitization. In summary, the integrated approaches revealed that Altertoxin X possesses a promising anticancer activity and could serve as a new therapeutic drug for breast cancer treatment.

Zinc oxide nanoparticles (ZnO-NPs) synthesized through biogenic methods have gained significant attention due to their unique properties and potential applications in various biological fields. Unlike chemical and physical approaches that may lead to environmental pollution, biogenic synthesis offers a greener alternative, minimizing hazardous environmental impacts. During biogenic synthesis, metabolites present in the biotic sources (like plants and microbes) serve as bio-reductants and bio-stabilizers. Among the biotic sources, microbes have emerged as a promising option for ZnO-NPs synthesis due to their numerous advantages, such as being environmentally friendly, non-toxic, biodegradable, and biocompatible. Various microbes like bacteria, actinomycetes, fungi, and yeast can be employed to synthesize ZnO-NPs. The synthesis can occur either intracellularly, within the microbial cells, or extracellularly, using proteins, enzymes, and other biomolecules secreted by the microbes. The main key advantage of biogenic synthesis is manipulating the reaction conditions to optimize the preferred shape and size of the ZnO-NPs. This control over the synthesis process allows tailoring the NPs for specific applications in various fields, including medicine, agriculture, environmental remediation, and more. Some potential applications include drug delivery systems, antibacterial agents, bioimaging, biosensors, and nano-fertilizers for improved crop growth. While the green synthesis of ZnO-NPs through microbes offers numerous benefits, it is essential to assess their toxicological effects, a critical aspect that requires thorough investigation to ensure their safe use in various applications. Overall, the presented review highlights the mechanism of biogenic synthesis of ZnO-NPs using microbes and their exploration of potential applications while emphasizing the importance of studying their toxicological effects to ensure a viable and environmentally friendly green strategy.

Breast cancer is a leading cause of mortality in women, and alternative therapies with fewer side effects are actively being explored. Breast cancer is a significant global health concern, and conventional treatments like radiotherapy and chemotherapy often have side effects. Medicinal plant extracts offer a promising avenue for the development of effective and safe anticancer therapies. Terminalia chebula, a plant known for its medicinal properties, was selected for investigation in this study. We aimed to assess the antiproliferative effects of TCF extract on breast cancer cells and explore the potential role of saccharopine, a phytochemical found in TCF, as an anticancer agent. MCF7 breast cancer cell lines were exposed to TCF extract, and cell viability and apoptosis assays were performed to evaluate the antiproliferative and apoptogenic effects. Molecular docking studies were conducted to assess the binding affinity of saccharopine with EGFRs. Molecular dynamics simulations and binding energy calculations were employed to analyze the stability of the EGFR-saccharopine complex. The TCF extract exhibited significant antiproliferative effects on MCF7 breast cancer cells and induced apoptosis in a dose-dependent manner. Molecular docking analysis revealed that saccharopine demonstrated a higher binding affinity with EGFR compared to the reference compound (17b-estradiol). The subsequent MDS simulations indicated stable binding patterns and conformation of the EGFR-saccharopine complex, suggesting a potential role in inhibiting EGFR-mediated signaling pathways. The investigation of Terminalia chebula fruit extract and its phytochemical saccharopine has revealed promising antiproliferative effects and a strong binding affinity with EGFR. These findings provide a foundation for future research aimed at isolating saccharopine and conducting in vivo studies to evaluate its potential as a targeted therapy for breast cancer. The development of novel anticancer agents from plant sources holds great promise in advancing the field of oncology and improving treatment outcomes for breast cancer patients.

A major part of any biological system on earth involves microorganisms, of which the majority are yet to be cultured. The conventional methods of culturing microbes have given fruitful outcomes yet have limitations. The curiosity for better understanding has led to the development of culture-independent molecular methods that help push aside the roadblocks of earlier methods. Metagenomics unifies the scientific community in search of a better understanding of the functioning of the ecosystem and its component organisms. This approach has opened a new paradigm in advanced research. It has brought to light the vast diversity and novelty among microbial communities and their genomes. This review focuses on the development of this field over time, the techniques and analysis of data generated through sequencing platforms, and its prominent interpretation and representation.

Introduction: The use of plant extracts in the green synthesis of metallic nanoparticles is one of the simplest, most practical, economical, and ecologically friendly methods for avoiding the use of toxic chemicals.Method: Silver nanoparticles (AgNPs) were synthesized, employing a high-efficiency, non- toxic, cost-effective, green, and simple technique that included the use of Salacia oblonga root extract (SOR) as a capping agent compared to synthetic nanoparticles. The use of S. oblonga can be seen in traditional medicines for treating diabetes, obesity, rheumatism, gonorrhea, asthma, and hyperglycemia. The objectives of the current study were to green synthesize S. oblonga root extract silver nanoparticles (SOR-AgNPs), characterize them, and study their antioxidant, antibacterial, and antidiabetic activities.Result: The shape of SOR-AgNPs was spherical, at less than 99.8 nm in size, and exhibited a crystalline peak at XRD. The green synthesized SOR-AgNPs showed significant antioxidant properties like DPPH (80.64 μg/mL), reducing power capacity (81.09 ± SEM μg/mL), nitric oxide (96.58 μg/mL), and hydroxyl (58.38 μg/mL) radical scavenging activities. The MIC of SOR-AgNPs was lower in gram-positive bacteria. The SOR-AgNPs have displayed efficient inhibitory activity against α-amylase, with an EC50 of 58.38 μg/mL. Analysis of capping protein around the SOR-AgNPs showed a molecular weight of 30 kDa.Discussion: These SOR-AgNPs could be used as antibacterial and antidiabetic drugs in the future as it is cheap, non-toxic, and environmentally friendly. Bio-fabricated AgNPs had a significant impact on bacterial strains and could be used as a starting point for future antibacterial drug development.

For many years, the primary focus has been on finding effective treatments for Alzheimer’s disease (AD), which has led to the identification of promising therapeutic targets. The necessity for AD stage-dependent optimal settings necessitated a herbal therapy strategy. The plant species Areca Catechu L. (AC) was selected based on the traditional uses against CNS-related diseases. AC leaf extract were prepared using a Soxhlet extraction method and hydroxyapatite nanoparticles (HAp-NPs) were synthesized from the same (AC-HAp-NPs). Powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and fourier transform infrared spectroscopy (FTIR) were used to confirm the structure and morphology of the as-prepared AC-HAp-NPs. The crystalline character of the AC-HAp-NPs was visible in the XRD pattern. The synthesized material was found to be nanoflake, with an average diameter of 15–20 nm, according to SEM analysis. The TEM and SAED pictures also revealed the form and size of AC-HAp-NPs. In vitro anti-acetylcholinesterase and butyrylcholinesterase (AChE and BChE) activities of hydroxyapatite nanoparticles produced from an AC leaf extract was tested in this study. When compared to control, AC-HAp-NPs had higher anti-AChE and BChE activity. The anti-acetylcholinesterase action of phytoconstituents generated from AC leaf extract was mediated by 4AQD and 4EY7, according to a mechanistic study conducted utilizing in silico research. The global and local descriptors, which are the underpinnings of Conceptual Density Functional Theory (CDFT), have been predicted through the MN12SX/Def2TZVP/H2O model chemistry to help in the comprehension of the chemical reactivity properties of the five ligands considered in this study. The CDFT experiments are supplemented by the calculation of several useful calculated pharmacokinetics indices, their expected biological targets connected to the bioavailability of the five ligands in order to further the goal of studying their bioactivity.

A series of novel enantiopure isoxazolidine derivatives were synthesized and evaluated for their anticancer activities against three human cancer cell lines such as human breast carcinoma (MCF-7), human lung adenocarcinoma (A-549), and human ovarian carcinoma (SKOV3) by employing MTT assay. The synthesized compounds were characterized by NMR and elemental analysis. Results revealed that all the synthesized compounds displayed significant inhibition towards the tested cell lines. Among them, 2g and 2f, which differ only by the presence of an ester group at the C-3 position and small EDG (methyl) at the C-5 position of the phenyl ring (2g), were the most active derivatives in attenuating the growth of the three cells in a dose-dependent manner. The IC50 for 2g were 17.7 ± 1 µM (MCF-7), 12.1 ± 1.1 µM (A-549), and 13.9 ± 0.7 µM (SKOV3), and for 2f were 9.7 ± 1.3µM (MCF-7), 9.7 ± 0.7µM (A-549), and 6.5 ± 0.9µM (SKOV3), respectively, which were comparable to the standard drug, doxorubicin. The enzymatic inhibition of 2f and 2g against EGFR afforded good inhibitory activity with IC50 of 0.298 ± 0.007 μM and 0.484 ± 0.01 µM, respectively, close to the positive control, Afatinib. Compound 2f arrested the cell cycle in the S phase in MCF-7 and SKOV3 cells, and in the G2/M phase in the A549 cell; however, 2g induced G0/G1 phase cell cycle arrest, and inhibited the progression of the three cancer cells, together with significant apoptotic effects. The docking study of compounds 2f and 2g into EGFR ATP-active site revealed that it fits nicely with good binding affinity. The pharmacokinetic and drug-likeness scores revealed notable lead-like properties. At 100 ns, the dynamic simulation investigation revealed high conformational stability in the EGFR binding cavity.

This study presents a green protocol for the fabrication of a multifunctional smart nanobiocomposite (NBC) (ZnO-PIACSB-TiO2) for secure antimicrobial and antibiofilm applications. First, shrimp shells were upgraded to a polyimidazolium amphiphilic chitosan Schiff base (PIACSB) through a series of physicochemical processes. After that, the PIACSB was used as an encapsulating and coating agent to manufacture a hybrid NBC in situ by co-encapsulating ZnONPs and TiO2NPs. The physicochemical and visual characteristics of the new NBC were investigated by spectral, microscopic, electrical, and thermal methods. The antimicrobial indices revealed that the newly synthesized, PIACSB-coated TiO2–ZnO nanocomposite is an exciting antibiotic due to its amazing antimicrobial activity (MIC/MBC→0.34/0.68 μg/mL, 0.20/0.40 μg/mL, and 0.15/0.30 μg/mL working against S. aureus, E. coli, and P. aeruginosa, respectively) and antifungal capabilities. Additionally, ZnO-PIACSB-TiO2 is a potential fighter of bacterial biofilms, with the results being superior to those of the positive control (Cipro), which worked against S. aureus (only 8.7% ± 1.9 biofilm growth), E. coli (only 1.4% ± 1.1 biofilm growth), and P. aeruginosa (only 0.85% ± 1.3 biofilm growth). Meanwhile, the NBC exhibits excellent biocompatibility, as evidenced by its IC50 values against both L929 and HSF (135 and 143 µg/mL), which are significantly higher than those of the MIC doses (0.24–24.85 µg/mL) that work against all tested microbes, as well as the uncoated nanocomposite (IC50 = 19.36 ± 2.04 and 23.48 ± 1.56 µg/mL). These findings imply that the new PIACSB-coated nanocomposite film may offer promising multifunctional food packaging additives to address the customer demand for safe, eco-friendly food products with outstanding antimicrobial and antibiofilm capabilities.

(E)-1-((((1H-benzo[d]imidazol-2-yl)methyl)imino)methyl)naphthalen-2-ol, ligand was synthesized by condensation of (1H-benzo[d]imidazol-2-yl) methanamine, with 2-hydroxynaphthaldehyde. The ligand and the metal complexes were characterized by various spectroscopic techniques. Interpretation of spectra confirmed that the ligand adopted either a neutral tridentate or a monobasic tridentate mode, bonded to the metal ions through the nitrogen atom of the heterocyclic benzimidazole, azomethine nitrogen atom and deprotonated phenolic oxygen atom forming either a square planer geometry. X-ray powder diffraction analysis of complexes indicated that the complexes were crystalline in nature with triclinic structures. The antibacterial and the antifungal activities of the ligand and its complexes were examined against Escherichia coli, Bacillus subtilis and Aspergillus niger by well- diffusion method. The results showed that Cd (II) complex exhibits the highest antifungal and antibacterial activities among the tested complexes. The in vitro antitumor activityies of the different complexes were tested and the results revealed an important cytotoxicity of cadmium complex against MCF-7, Hep G2 and HCT 116 cell. Iron complex showed also a strong toxicity towards Hep G2 and HCT cell whereas moderate activity against MCF-7. The bioassay study of different complexes against mosquito larvae demonstrated strong activity of zirconium complex with 0.172 values of LC50.

Avermectins are used in animals and humans for their broad-spectrum effects against parasites causing cytotoxicity and damage to the cellular DNA. In this study, we examined the toxicological changes of ivermectin (IVM) and doramectin (DME) with or without the co-administration of vitamin E (Vit. E) and selenium (Se). The drugs used were for animal use. Twenty-five adult male rats were divided into five groups. Group 1 (control) was given saline, Group 2 was given IVM (0.2 mg/kg b.w.), Group 3 was given IVM and Vit. E/Se (80/1.6 mg/kg b.w., respectively), Group 4 received DME (0.2 mg/kg b.w.), and Group 5 received DME and Vitamin E/Se. Both IVM and DME were given by subcutaneous injections whereas Vit. E and Se were given orally. All the treatments were given once per week throughout the eight weeks. Although the doses were off-label use, they were given in a long-term course to unveil their toxicity effects in a clear manner and the response of the amelioration. By 24-h after the 8th week, the rats were sacrificed. Their blood was sampled for the haematological and serobiochemical examinations. Histopathological changes and caspase-3 were determined in the hepatic and renal tissues. The histopathological findings showed that Vit. E and Se reduced the cellular changes induced by IVM or DME, indicating that Vit. E and Se protect against both types of avermectins, and that DME was safer than IVM. The cytotoxicity was assessed on a human embryo kidney (HEK) and skin cells by the SRB/IC50 method and AO/EB (acridine orange-ethidium bromide) staining. Both IVM and DME caused apoptosis in the cultured HEK more than in the skin cells (80% vs. 30%, respectively). The cellular apoptosis in response to the IVM was more than that of DME, and the use of Vit. E and Se reduced the cytotoxicity as observed by caspase-3, in vivo, and IC50, in vitro.

In the present study, the binding affinity of 52 bioactive secondary metabolites from Wedelia trilobata towards the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein (PDB: 2W3L) structure was identified by using in silico molecular docking and molecular dynamics simulation. The molecular docking results demonstrated that the binding energies of docked compounds with Bcl-2 protein ranged from −5.3 kcal/mol to −10.1 kcal/mol. However, the lowest binding energy (−10.1 kcal/mol) was offered by Friedelin against Bcl-2 protein when compared to other metabolites and the standard drug Obatoclax (−8.4 kcal/mol). The molecular dynamics simulations revealed that the Friedelin-Bcl-2 protein complex was found to be stable throughout the simulation period of 100 ns. Overall, the predicted Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of Friedelin are relatively better than Obatoclax, with the most noticeable differences in many parameters where Friedelin has no AMES toxicity, hepatotoxicity, and skin sensitization. The ADMET profiling of selected compounds supported their in silico drug-likeness properties. Based on the computational analyses, the present study concluded that Friedelin of W. trilobata was found to be the potential inhibitor of the Bcl-2 protein, which merits attention for further in vitro and in vivo studies before clinical trials.

This work reports a new approach for the synthesis of extremely small monodispersed silver nanoparticles (AgNPs) (2.9–1.5) by reduction of silver nitrate in a new series of benzyl alkyl imidazolium ionic liquids (BAIILs)-based microemulsions (3a–f) as media and stabilizing agents. Interestingly, AgNPs isolated from the IILMEs bearing the bulkiest substituents (tert-butyl and n-butyl) (3f) displayed almost no nanoparticle agglomeration. In an in vitro antibacterial test against ESKAPE pathogens, all AgNPs-BAIILs had potent antibiotic activity, as reflected by antibacterial efficiency indices. Furthermore, when compared to other nanoparticles, these were the most effective in preventing biofilm formation by the tested bacterial strains. Moreover, the MTT assay was used to determine the cytotoxicity of novel AgNPs-BAIILs on healthy human skin fibroblast (HSF) cell lines. The MTT assay revealed that novel AgNPs-BAIILs showed no significant toxic effects on the healthy cells. Thus, the novel AgNPs-BAIILs microemulsions could be used as safe antibiotics for skin bacterial infection treatments. AgNPs isolated from BAIIL (3c) was found to be the most effective antibiotic of the nanoparticles examined.

Bacterial infections are one of the leading causes of morbidity, mortality, and healthcare complications in patients. Leptospirosis is found to be the most prevalent, re-emergent, and neglected tropical zoonotic disease worldwide. The adaptation to various environmental conditions has made Leptospira acquire a large genome (~4.6 Mb) and a complex outer membrane, making it unique among bacteria that mimic the symptoms of jaundice and hemorrhage. Sph2 is another important virulence factor that enhances hemolytic sphingomyelinase—capable of moving inside mitochondria—which increases the ROS level and decreases the mitochondrial membrane potential, thereby leading to cell apoptosis. In the present study, 25 suspected bovine serum samples were subjected to the Microscopic Agglutination Test (MAT) across the Mysuru region. Different samples, such as urine, serum, and aborted materials from the confirmed MAT-positive animals, were used for isolation and genomic detection by conventional PCR targeting virulence gene, Lipl32, using specific primers. Further, in vitro and in silico studies were performed on isolated cultures to assess the anti-leptospiral, anti-hemolytic, and sphingomyelinase enzyme inhibition using novel pseudopeptides. The microdilution technique (MDT) and dark field microscope (DFM) assays revealed that at a concentration of 62.5 μg/mL, the pseudopeptide inhibited 100% of the growth of Leptospira spp., suggesting its efficiency in the treatment of leptospirosis. The flow cytometry analyses show the potency of the pseudopeptide against sphingomyelinase enzymes using human umbilical vein endothelial cells (HUVECs). Thus, the present study demonstrated the efficacy of the pseudopeptide in the inhibition of the growth of Leptospira, and therefore, this can be used as an alternative drug for the treatment of leptospirosis.

The emerging interest in the field of coordination chemistry and their biological applications has created a novel impact in the field of chemical biology. With this motivation, in this work we have synthesized a novel benzimidazole derived imine ligand, 2-((E)-((1H-benzo[d]-2-yl)methylimino)methyl)-4-fluorophenol (HBMF) and its Co(III) and Cu(II) complexes. The metal complexes (C1–C4) were synthesized in 2:1 (HBMF: metal ion) and 1:1:1 (HBMF: metal ion: 1,10-phen) ratios. Structural elucidations of all the synthesized compounds were performed using FT-IR, UV-Visible, NMR, Mass spectroscopy and elemental analysis techniques. A combination of first principles calculations and molecular dynamics simulations was applied to computationally investigate the structural, reactive, and spectroscopic properties of the newly synthesized HBMF ligand and its complexes with copper and cobalt metal ions. Quantum-mechanical calculations in this study were based on the density functional theory (DFT), while molecular dynamics (MD) simulations were based on the OPLS4 force field. The DFT calculations were used to obtain the reactive and spectroscopic properties of the ligand and its complexes, while molecular dynamics (MD) simulations were used to address the ligand’s reactivity with water. Further, the in vitro anti-proliferative activity of the compounds was tested against the A549, Ehrlich–Lettre ascites carcinoma (EAC), SIHA and NIH3T3 cell lines. The biological results depicted that the compound C4, with molecular formula C27H23Cl2CoFN5O3 exhibited profound anti-proliferative activity against the EAC cell line with a significant IC50 value of 10 µm when compared to its parent ligand and other remaining metal complexes under study. Various assays of hematological parameters (alkaline phosphate, creatinine, urea, RBC and WBC) were performed, and significant results were obtained from the experiments. Furthermore, the effect of C4 on neovascularization was evaluated by stimulating the angiogenesis with rVEGF165, which was compared with non-tumor models. The EAC cells were cultured in vivo and administrated with 50 and 75 mg/kg of two doses and tumor parameters were evaluated.

The emergence of resistance by biofilm-forming bacteria has reached alarming and dangerous levels that threaten human civilization. The current study sought to investigate the antibiofilm potential of green-synthesized silver nanoparticles, mediated by a new Streptomyces strain. Zeta potential, transmission electron microscopy (TEM), and UV-Vis spectroscopy were used to analyze the biosynthesized AgNPs. Results revealed that silver nanoparticles had a size of (5.55 and 45.00 nm) nm and a spherical shape, with surface plasmon resonance (SPR) absorption at 400–460 nm in the UV-vis spectra establishing the formation of Streptomyces-Ag-NPs. The biosynthesized AgNPs showed a pronounced antibacterial efficacy against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus. Moreover, the obtained Streptomyces-AgNPs exerted biofilm inhibition activity against nosocomial hospital-resistant bacteria, including Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. The mechanism of biogenic AgNPs antibacterial action was visualized using TEM, which indicated the AgNPs accumulation and disruption of bacterial cell membrane function. Additionally, a molecular docking study was conducted to evaluate the binding mode of AgNPs with an Escherichia coli outer membrane. Furthermore, the cytotoxic profile of the AgNPs was evaluated toward three cell lines (MCF-7, HepG2 & HCT 116), and the low cytotoxic effects of the obtained nanoparticles indicated their possible medical application with low risks to human health.

The present work describes the chemical preparation of Schiff bases derived from 4,4′-diaminodiphenyl sulfone (L1–L5) and their Co(II) metal complexes. The evaluation of antimicrobial and anticancer activities against MCF-7 cell line and human lung cancer cell line A-549 was performed. The aforementioned synthesized compounds are characterized by spectroscopic techniques and elemental analysis confirms successful synthesis. The results from the above analytical techniques revealed that the complexes are in an octahedral geometry. The antimicrobial activity of the synthesized Schiff base ligands and their metal complexes under study was carried out by using the agar well diffusion method. The ligand and complex interactions for biological targets were predicted using molecular docking and high binding affinities. Further, the anticancer properties of the synthesized compounds are performed against the MCF-7 cell line and human lung cancer cell line A-549 using adriamycin as the standard drug.

The ever-expanding pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has gained attention as COVID-19 and caused an emergency in public health to an unmatched level to date. However, the treatments used are the only options; currently, no effective and licensed medications are available to combat disease transmission, necessitating further research. In the present study, an in silico-based virtual screening of anti-HIV bioactive compounds from medicinal plants was carried out through molecular docking against the main protease (Mpro) (PDB: 6LU7) of SARS-CoV-2, which is a key enzyme responsible for virus replication. A total of 16 anti-HIV compounds were found to have a binding affinity greater than −8.9 kcal/mol out of 150 compounds screened. Pseudohypericin had a high affinity with the energy of −10.2 kcal/mol, demonstrating amino acid residual interactions with LEU141, GLU166, ARG188, and GLN192, followed by Hypericin (−10.1 kcal/mol). Moreover, the ADME (Absorption, Distribution, Metabolism and Excretion) analysis of Pseudohypericin and Hypericin recorded a low bioavailability (BA) score of 0.17 and violated Lipinski’s rule of drug-likeness. The docking and molecular simulations indicated that the quinone compound, Pseudohypericin, could be tested in vitro and in vivo as potent molecules against COVID-19 disease prior to clinical trials.This was also supported by the theoretical and computational studies conducted. The global and local descriptors, which are the underpinnings of Conceptual Density FunctionalTheory (CDFT) have beenpredicted through successful model chemistry, hoping that they could be of help in the comprehension of the chemical reactivity properties of the molecular systems considered in this study.

Dementia is reported to be common in those with type 2 diabetes mellitus. Type 2 diabetes contributes to common molecular mechanisms and an underlying pathology with dementia. Brain cells becoming resistant to insulin leads to elevated blood glucose levels, impaired synaptic plasticity, microglial overactivation, mitochondrial dysfunction, neuronal apoptosis, nutrient deprivation, TAU (Tubulin-Associated Unit) phosphorylation, and cholinergic dysfunction. If insulin has neuroprotective properties, insulin resistance may interfere with those properties. Risk factors have a significant impact on the development of diseases, such as diabetes, obesity, stroke, and other conditions. Analysis of risk factors of importance for the association between diabetes and dementia is important because they may impede clinical management and early diagnosis. We discuss the pathological and physiological mechanisms behind the association between Type 2 diabetes mellitus and dementia, such as insulin resistance, insulin signaling, and sporadic forms of dementia; the relationship between insulin receptor activation and TAU phosphorylation; dementia and mRNA expression and downregulation of related receptors; neural modulation due to insulin secretion and glucose homeostasis; and neuronal apoptosis due to insulin resistance and Type 2 diabetes mellitus. Addressing these factors will offer clinical outcome-based insights into the mechanisms and connection between patients with type 2 diabetes and cognitive impairment. Furthermore, we will explore the role of brain insulin resistance and evidence for anti-diabetic drugs in the prevention of dementia risk in type 2 diabetes.

Annona glabra L. (AngTE) and Annona squamosa L. (AnsTE) fruits have been widely used in cancer treatment. Accordingly, their extracts were used to synthesize silver nanoparticles via a biogenic route (Ang-AgNPs) and (Ans-AgNPs), respectively. Chemical profiling was established using UPLC-QTOF-MS/MS. All species were tested for anticancer activity against human cervical cancer cells (HeLa), prostate adenocarcinoma metastatic (PC3), and ovary adenocarcinoma (SKOV3) using sulphorhodamine B assay. Apoptosis was determined using Annexin flow cytometry along with cell cycle analysis and supported by a molecular docking. The antibacterial and synergistic effect when combined with gentamicin were evaluated. A total of 114 compounds were tentatively identified, mainly acetogenins and ent-kaurane diterpenes. AnsTE and Ans-AgNPs had the most potent cytotoxicity on HeLa and SKOV3 cells, inducing a significant apoptotic effect against all tumor cells. The AnsTE and Ans-AgNPs significantly arrested PC3, SKOV3, and HeLa cells in the S phase. The nanoparticles demonstrated greater antibacterial and antifungal activities, as well as a synergistic effect with gentamicin against P. aeruginosa and E. coli. Finally, a molecular docking was attempted to investigate the binding mode of the identified compounds in Bcl-2 proteins’ receptor, implying that the fruits and their nanoparticles are excellent candidates for treating skin infections in patients with ovarian or prostatic cancer.

In the current study, new benzimidazole-based 1,3,4-oxadiazole derivatives have been synthesized and characterized by NMR, IR, MS, and elemental analysis. The final compounds were screened for cytotoxicity against MDA-MB-231, SKOV3, and A549 cell lines and EGFR for inhibitory activities. Compounds 10 and 13 were found to be the most active against all the tested cell lines, comparable to doxorubicin, and exhibited significant inhibition on EGFR kinase, with IC50 0.33 and 0.38 μM, respectively, comparable to erlotinib (IC50 0.39 μM). Furthermore, these two compounds effectively suppressed cell cycle progression and induced cell apoptosis in MDA-MB-231, SKOV3, and A549 cell lines. The docking studies revealed that these compounds showed interactions similar to erlotinib at the EGFR site. It can be concluded that the synthesized molecules effectively inhibit EGFR, can arrest the cell cycle, and may trigger apoptosis and therefore, could be used as lead molecules in the development of new anticancer agents targeting EGFR kinase.

Herein we describe the synthesis of a series of nickel(II) complexes (C1–C3) with Schiff bases (HL1–HL3) derived from 4-amino-5-mercapto-3-methyl-1,2,4-triazole and ortho/meta/para-nitrobenzaldehyde having composition [Ni(L)2(H2O)2]. The obtained ligands and their complexes were characterized using physico-chemical techniques viz., elemental analysis, magnetic moment study, spectral (electronic, FT-IR, 1H-NMR) and thermal analysis. The elemental analysis and spectral analysis revealed that Schiff bases behave as monoanionic bidentate ligands towards the Ni(II) ion. Whereas, the magnetic moment study suggested the octahedral geometry of all the Ni(II) complexes. The thermal behavior of the complexes has been studied by thermogravimetric analysis and agrees well with the composition of complexes. Further, the biological activities such as antimicrobial and antifungal studies of the Schiff bases and Ni(II) complexes have been screened against bacterial species (Staphylococcus aureus and Pseudomonas aeruginosa) and fungal species (Aspergillus niger and Candida albicans) activity by MIC method, the results of which revealed that metal complexes exhibited significant antimicrobial activities than their respective ligands against the tested microbial species. Furthermore, the molecular docking technique was employed to investigate the active sites of the selected protein, which indeed helped us to screen the potential anticancer agents among the synthesized ligand and complexes. Further, these compounds have been screened for their in vitro anticancer activity using OVCAR-3 cell line. The results revealed that the complexes are more active than the ligands.

The current approach described the synthesis of a new series of indolylpyrrole derivatives through multicomponent reaction of α-cyano chalcones, appropriate aldehydes, and ammonium acetate in refluxed acetic acid. The chemical structures of the designed compounds were confirmed with spectroscopic data and elemental analysis and then tested for their in vitro cytotoxic activity by SRB assay method towards three cell lines involving human Prostate adenocarcinoma; metastatic cells (PC-3), human ovary adenocarcinoma (SKOV3) and human dukes' type B, colorectal adenocarcinoma (LS 174 T). Most significant activity provided with compounds 5c, 5h and, 5j against prostate cancer cells (PC-3) with IC50s of 3.30 ± 0.20, 3.60 ± 0.10, and 3.60 ± 0.90 µg/ml, respectively. In human ovarian carcinoma (SKOV3), the compounds 5a, and 5i have stronger cytotoxicity with IC50s of 1.20 ± 0.04, 1.90 ± 0.50 µg/ml, respectively than the standard doxorubicin (IC50 = 2.20 ± 0.02 µg/ml). On the other hand, only compound 5a has the ability to diminish the viability of LS174T cells in an active manner with IC50 2.80 ± 0.10 µg/ml. Consequently, this effort offers groundwork for additional examination of nominated indolylpyrroles as antiproliferative agents.

(1) Background: Virgin olive oil (VOO) has attracted the attention of many researchers due to its nutritional and medicinal values. However, VOO’s biological applications have been limited due to a lack of precise chemical profiling and approach to increase the physicochemical characteristics, bioactivity, and delivery of its bioactive components; (2) Methods: The current study intended to evaluate the chemical composition of VOO using the GC-MS technique and determine its major components. Furthermore, the effect of incorporating VOO into Tween 80-lecithin nanoemulsion (OONE) and a quaternized trimethyl chitosan-thiol (TMCT) hydrogel-thickened nanoemulsion system (OOHTN) on its physicochemical characteristics and biological potentials will be investigated; (3) Results: The VOO-based NEs’ physicochemical properties (particle size and zeta potential) were steady during storage for four weeks owing to the inclusion of the protective TMCT hydrogel network to OONE. Excessive fine-tuning of olive oil nanoemulsion (OONE) and the TMCT protective network’s persistent positive charge have contributed to the oil’s improved antimicrobial, anti-biofilm, and antioxidant potentials; (4) Conclusions: The Tween 80-lecithin-TMCT nanosystem might provide a unique and multifunctional nanoplatform for efficient topical therapy as well as the transdermal delivery of lipophilic bioactive compounds.

(1) Background: Thymus vulgaris L. (thyme) essential oil (TEO) has gained much attention because of its long history of medicinal usage. However, the lack of precise chemical profiling of the TEO and methods to optimize the bioactivity and delivery of its constituents has hampered its research on quality control and biological function; (2) Methods: The current study aimed to analyze the TEO’s chemical composition using the GC-MS method and identify its key components. Another objective of this work is to study the impact of the protective layer of amphiphilic oligochitosan (AOC) on the physicochemical stability and transdermal potentials of TEO multilayer nanoemulsions formulated by the incorporation of TEO, Tween80, lecithin (Lec), and AOC; (3) Results: The AOC protective layer significantly improved the stability of TEO-based NEs as revealed by the constancy of their physicochemical properties (particle size and zeta potential) during storage for a week. Excessive fine-tuning of thyme extract NEs and the AOC protective layer’s persistent positive charge have been contributed to the thyme extract’s improved anti-inflammatory, transdermal, and anti-melanoma potentials; (4) Conclusions: the AOC-coated NEs could offer novel multifunctional nanoplatforms for effective transdermal delivery of lipophilic bioactive materials.

Chromatographic investigation of the aerial parts of the Rhazya stricta (Apocynaceae) resulted in the isolation of two new monoterpene indole alkaloids, 6-nor-antirhine-N1-methyl (1) and razyamide (2), along with six known compounds, eburenine (3), epi-rhazyaminine (4), rhazizine (5), 20-epi-sitsirikine (6), antirhine (7), and 16-epi-stemmadenine-N-oxide (8). The chemical structures were established by various spectroscopic experiments. Compounds 1–8 exhibited cytotoxic effects against three cancer cells with IC50 values ranging between 5.1 ± 0.10 and 93.2 ± 9.73 µM against MCF-7; 5.1 ± 0.28 and 290.2 ± 7.50 µM against HepG2, and 3.1 ± 0.17 and 55.7 ± 4.29 µM against HeLa cells. Compound 2 showed the most potent cytotoxic effect against all cancer cell lines (MCF-7, HepG2 and HeLa with IC50 values = 5.1 ± 0.10, 5.1 ± 0.28, and 3.1 ± 0.17 µM, respectively). Furthermore, compound 2 revealed a significant increase in the apoptotic cell population of MCF-7, HepG2, and HeLa cells, with 31.4 ± 0.2%, 29.2 ± 0.5%, and 34.9 ± 0.6%, respectively. Compound 2 decreased the percentage of the phagocytic pathway on HepG2 cells by 15.0 ± 0.1%. These findings can explain the antiproliferative effect of compound 2.

We aimed to evaluate the anticancer potential of crude venom (CV), γ irradiated Certastes cerastes venom (IRRV), and propolis ethanolic extract (PEE). IRRV showed a higher toxicity than CV, while CV-PEE showed higher toxicity than IRRV and CV against lung [A549] and prostate [PC3] cancer cells. Toxicity to [A549] and [PC3] cells was concentration and cell type dependent. In comparison to controls, apoptotic genes showed a significant upregulation of P53 and Casp-3 and a downregulation of Bcl-2. Also, induced elevated DNA accumulation in the [S] phase post PC3 cell treatment with IRRV and CV, as well as a significant DNA accumulation at G2/M phase after IRRV treatment of A549 cells. In contrast, PC3 cells showed a negligible cellular DNA accumulation after PEE treatment. Glutathione reductase [GR] was reduced in case of PC3 and A549 cell treated with IRRV, CV, and PEE compared with its values in untreated cell control. The Malondialdehyde [MDA] values in both cells recorded a significant elevation post IRRV treatment compared to the rest of the treatment regimen and untreated cell control. Similarly, IRRV and CV-PEE mix showed obviously higher reactive oxygen species [ROS] values than PC3 and A549 cell treatments with CV and PEE.

A library of novel naproxen based 1,3,4-oxadiazole derivatives (8–16 and 19–26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hybrids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15) was the most potent compound against MCF-7 and HepG2cancer cells with IC50 of 2.13 and 1.63 µg/mL, respectively, and was equipotent to doxorubicin (IC50 1.62 µg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC50 0.41 μM compared to standard drug Erlotinib (IC50 0.30 μM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy.

The anticancer activity of terretonin N (1) and butyrolactone I (2), obtained from the thermophilic fungus Aspergillus terreus TM8, was intensively studied against prostate adenocarcinoma (PC-3) and ovary adenocarcinoma (SKOV3) human cell lines. According to this study, both compounds showed potent cytotoxicity towards ovarian adenocarcinoma cells (SKOV3) with IC50 1.2 and 0.6 μg/mL, respectively. With respect to metastatic prostate cells (PC-3), the two compounds 1 and 2 showed a significantly promising cytotoxicity effect with IC50 of 7.4 and 4.5 μg/mL, respectively. The tested fungal metabolites showed higher rates of early and late apoptosis with little or no necrotic apoptotic pathway in all treated prostate adenocarcinoma (PC-3) and ovary adenocarcinoma (SKOV3) human cell lines, respectively. The results reported in this study confirmed the promising biological properties of terretonin N (1) and butyrolactone I (2) as anticancer agents via the induction of cellular apoptosis. However, further studies are needed to elucidate the molecular mechanism by which cellular apoptosis is induced in cancer cells.

From the soft coral Xenia umbellata, seven isoprenoid derivatives were isolated, including a new xenicane diterpene, xeniolide O (5) and a new gorgostane derivative gorgst-3β,5α,6β,11α,20(S)-pentol-3-monoacetate (7), along with three known sesquiterpenes (1–3), a known diterpene (4), and a known steroid (6). The extensive analyses of the NMR, IR, and MS spectral data led to determination of their chemical structures. Compounds 1–7 displayed a cytotoxic effect against breast adenocarcinoma (MCF-7), hepatocellular carcinoma (HepG2), and cervix adenocarcinoma (HeLa), with IC50 values ranging between 1.5 ± 0.1–23.2 ± 1.5; 1.8 ± 0.1–30.6 ± 1.1 and 0.9 ± 0.05–12.8 ± 0.5 μg/mL, respectively. Compound 3 showed potent cytotoxic effects against MCF-7, HepG2, and HeLa with IC50 values = 2.4 ± 0.20, 3.1 ± 0.10 and 0.9 ± 0.05 μg/mL, respectively. Compounds 2, 5, and 7 displayed cytotoxic effect against Hela cells with IC50 values = 12.8 ± 0.50, 6.7 ± 1.00 and 11.5 ± 2.20 μg/mL, respectively. Two DNA binding dyes, acridine orange (AO) and ethidium bromide (EtBr) were used for the detection of viable, apoptotic, and necrotic cells. The early apoptotic cell death was observed in all types of treated cells. The late apoptotic cells were highly present in HepG2 cells. Compounds 5 and 7 induced a high percentage of necrosis towards HepG2 and HeLa cells. The late apoptosis was recorded as a high rate after treatment with 7 on all cancer cells.

L-glutaminase is an important anticancer agent that is used extensively worldwide by depriving cancer cells of L-glutamine. The marine bacterium, Halomonas meridian was isolated from the Red Sea and selected as the more active L-glutaminase-producing bacteria. L-glutaminase fermentation was optimized at 36 h, pH 8.0, 37 °C, and 3.0% NaCl, using glucose at 1.5% and soybean meal at 2%. The purified enzyme showed a specific activity of 36.08 U/mg, and the molecular weight was found to be 57 kDa by the SDS-PAGE analysis. The enzyme was highly active at pH 8.0 and 37 °C. The kinetics’ parameters of Km and Vmax were 12.2 × 10−6 M and 121.95 μmol/mL/min, respectively, which reflects a higher affinity for its substrate. The anticancer efficiency of the enzyme showed significant toxic activity toward colorectal adenocarcinoma cells; LS 174 T (IC50 7.0 μg/mL) and HCT 116 (IC50 13.2 μg/mL). A higher incidence of cell death was observed with early apoptosis in HCT 116 than in LS 174 T, whereas late apoptosis was observed in LS 174 T more than in HCT 116. Also, the L-glutaminase induction nuclear fragmentation in HCT 116 was more than that in the LS 174T cells. This is the first report on Halomonas meridiana as an L-glutaminase producer that is used as an anti-colorectal cancer agent.

Diabetes is a major health problem that is associated with high risk of various complications. Medicinal plants hold great promise against diabetes. The traditional use of Cleome droserifolia as an antidiabetic agent was correlated to its flavonol glycosides content. In the current study, five major flavonol glycosides appeared on the RP-HPLC chromatogram of the aqueous extract namely; quercetin-3-O-β-d-glucosyl-7-O-α-rhamnoside (1), isorhamnetin-7-O-β-neohesperidoside (2), isorhamnetin-3-O-β-d-glucoside (3) kaempferol-4′-methoxy-3,7-O-α-dirhamnoside (4), and isorhamnetin-3-O-α-(4″-acetylrhamnoside)-7-O-α-rhamnoside (5). The inhibitory activities of these compounds were tested in vitro against several enzymes involved in diabetes management. Only the relatively less polar methoxylated flavonol glycosides (4, 5) showed mild to moderate α-amylase and α-glucosidase inhibitory activities. Compounds 1–4 displayed remarkable inhibition of dipeptidyl peptidase IV (DPPIV) enzyme (IC50 0.194 ± 0.06, 0.573 ± 0.03, 0.345 ± 0.02 and 0.281 ± 0.05 µg/mL, respectively) comparable to vildagliptin (IC50 0.154 ± 0.02 µg/mL). Moreover, these compounds showed high potential in preventing diabetes complications through inhibiting aldose reductase enzyme and combating oxidative stress. Both isorhamnetin glycoside derivatives (2, 3) exhibited the highest activities in aldose reductase inhibition and compound 2 (IC50 5.45 ± 0.26 µg/mL) was even more potent than standard quercetin (IC50 7.77 ± 0.43 µg/mL). Additionally, these flavonols exerted excellent antioxidant capacities through 2, 2-diphenyl-1-picrylhydrazil (DPPH) and ferric reducing antioxidant (FRAP) assays.

The present study surveyed the flora of the Jebel Fayfa region, South-West Saudi Arabia to analyze four elements of the vegetation: floristic diversity, life form, lifespan, and phytogeographical affinities. A total of 341 species of vascular plants were recorded belonging to 240 genera in 70 families, of which 101 species distributed among 40 families were considered as new additions to the flora of Jabal Fayfa. Six species are considered endemic to the study area while 27 are endangered. The most represented families were Fabaceae, Asteraceae, and Poaceae. The flora of Jabal Fayfa exhibited a high degree of monotypism. A total of 20 families (28.57%) were represented by a single species, and 180 genera (75.00%) were monotypic. The recorded flora consists of 70.09% perennials and 29.91% annuals. Phanerophytes and therophytes were the most frequent lifeforms. Phytogeographical analysis revealed that the biregional elements of the Saharo-Arabian/Sudano-Zambezian chorotype are the most dominant chorotypes (35.48%), forming two-thirds of the floristic structure in Jabal Fayfa. The new additions to the local flora of the region indicate that the Jabal Fayfa region and the country need further thorough botanical exploration and documentation which would help in adding several species to the flora of Saudi Arabia.

A new series of pyrazole 4–7 and pyrazolo[1,5-a]pyrimidine 8–13 were synthesized by using a simple, efficient procedure, and screened for their in-vitro antimicrobial and antitumor activities. Symmetrical and asymmetrical 3,6-diarylazo-2,5,7-triaminopyrazolo[1,5-a]pyrimidine were synthesized by the conventional method and also subjected to microwave irradiation and under ultrasound conditions. The biological results revealed that most of the tested compounds proved to be active as antibacterial and antifungal agents. The antitumor activity of the synthesized compounds was evaluated against human cancer cell lines, MCF-7, HCT-116, and HepG-2, as compared with Doxorubicin as a control.