Potential Agents Research Articles

Plasma activated solution synergistic with exogenous RONS enhances cancer cell apoptosis for improved tumor therapy

Abstract The role of reactive oxygen and nitrogen species (RONS) in plasma-activated solution (PAS) for inducing cancer cell apoptosis is well-established, but suboptimal concentrations and rapid degradation often limit their efficacy. This study addresses a significant gap in current research by exploring how the incorporation of exogenous RONS into PAS can enhance apoptosis in cancer cells, potentially overcoming the limitations of traditional PAS treatments. In this study, the effect of treating saline with a plasma jet for different durations was investigated to analyze how its chemical composition triggers apoptosis in cancer cells in vitro. It was observed that longer plasma treatment times resulted in lower cell viability, the reactive species of H2O2, NO2- and ONOO- were found to play a crucial role in inducing apoptosis in cancer cells. Based on these findings, the anticancer efficacy of PAS was further evaluated after the addition of specific exogenous RONS, using measures such as cell viability, intracellular ROS levels, and microscopic imaging. Biological experiments demonstrated that the anticancer efficacy followed the order: addition of RONS to saline before plasma discharge treatment > addition of RONS to saline after plasma discharge treatment > exogenous RONS solution without plasma treatment. This suggests that the external introduction of RONS can modify the chemical composition of PAS to effectively enhance its anticancer properties, with the addition of H2O2 before plasma discharge treatment proving to be the most effective strategy. These results provide a novel perspective on harnessing the anticancer potential of PAS and expanding its potential applications in tumor therapy.

A Synthetic Route Towards Spiro Indanone Fused Pyrano[2,3‐c]Chromene Derivatives via Oxa–Diels–Alder Reaction: Computational Investigation, Antibacterial Evaluation and Molecular Docking Studies as Potential DNA Gyrase Inhibitors

ABSTRACTA highly efficient method for the synthesis of 2′H‐spiro[indene‐2,3′‐pyrano[2,3‐c]chromene] derivatives 20(a–s) has been developed involving oxa–Diels–Alder reaction as the key step under conventional conditions in good to excellent yields. The compounds were all characterized using 1H, 13C NMR, HRMS, and X‐ray crystallography. The present study employs DFT to validate the reaction pathway. In vitro antibacterial assay of all the synthesized derivatives was evaluated against Gram‐negative Escherichia coli and Gram‐positive Staphylococcus aureus bacterial strains. Compound 20e was found to be the most potent molecule with ZI of 19 mm and MIC of 16 μg mL−1 in E. coli and ZI of 14 mm and MIC of 32 μg mL−1 in S. aureus. Additionally, 20e demonstrated a strong inhibition of DNA gyrase in silico, with a binding affinity of −9.3 and − 9.0 kcal/mol in E. coli and S. aureus respectively. Also, significant pharmacokinetic, physicochemical, and drug‐like properties of the spirocyclic compounds were further corroborated by ADME investigations. Hence, these new series of spiro indanone fused pyrano[2,3‐c]chromene derivatives may be potent druggable antibacterial agents in future.

Benzylpiperazinyl derivatives of alepterolic acid: Synthesis and cytotoxic evaluation.

Natural products play a significant role in the development of modern drugs. Alepterolic acid, a labdane-type diterpenoid firstly isolated from Aleuritopteris argentea (Gmél.) Fée, has been identified as a valuable template for the synthesis of potent anticancer agents by structural modification. In this study, a series of new derivatives was obtained by coupling alepterolic acid with benzylpiperazines. It was found that (3,4-dichlorobenzyl)piperazinyl alepterolic acid (compound 6p) displayed the most toxic against MCF-7 cell line, with IC50 value of 8.31±0.67 μM. Further investigations demonstrated that compound 6p induced morphological changes in MCF-7 cells, inhibited proliferation in a time- and dose-dependent manner. Furthermore, western blot analysis revealed that compound 6p induced a significant increase in cleaved caspase-9, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP) and Bax/Bcl2 ratio in MCF-7 cells. All of these results confirmed that compound 6p induced endogenous apoptosis in MCF-7 cells. Conclusively, the findings suggest that the incorporation of benzylpiperazine to alepterolic acid represents a promising approach for the discovery of new drug candidates.

Exploring the green synthesis of silver nanoparticles using natural extracts and their potential for cancer treatment.

Silver nanoparticles (AgNPs) have attracted increasing attention in nanomedicine, with versatile applications in drug delivery, antimicrobial treatments, and cancer therapies. While chemical synthesis remains a common approach for AgNP production, ensuring environmental sustainability requires a shift toward eco-friendly, "green" synthesis techniques. This article underscores the promising role of plant extracts in the green synthesis of AgNPs, highlighting the importance of their natural sources and diverse bioactive compounds. Various characterization methods for these nanomaterials are also reviewed. Furthermore, the anticancer potential of green AgNPs (Gr-AgNPs) is examined, focusing on their mechanisms of action and the challenges to their clinical implementation. Finally, future directions in the field are discussed.

Synthesis of Sulfonamide-Based Schiff Bases as Potent Anticancer Agents: Spectral Analyses, Biological Activity, Molecular Docking, ADME, DFT, and Pharmacophore Modelling Studies.

The current study focuses on the synthesis and characterization of six benzenesulfonamide-based Schiff base derivatives (7-12) with various electron-withdrawing and electron-donating substituents (-F, -CI, -Br, -CH3, and -OCH3) and the assessment of their antiproliferative activities against human lung (A549) and liver (HepG2) cancer cell lines using in vitro and in silico approaches. The structures of the synthesized compounds (7-12) were elucidated by elemental analysis and FT-IR, 1D (1H, 13C, APT, and DEPT-135), and 2D (HMQC and HMBC) NMR spectroscopies. The cytotoxic activities of the targeted compounds were determined at various concentrations against these cancer cell lines for 72 h, using the MTT method. The targeted molecules (7-12) demonstrated remarkable antiproliferative activities, with IC50 values ranging from 6.032-9.533 μM against the A549 cell line and 5.244-9.629 μM against the HepG2 cell line. These compounds showed activities at lower or very similar concentrations to cisplatin against the A549 cell line and at much lower concentrations than cisplatin against the HepG2 cell line. Among them, compounds 10 and 12 were found to be more effective against A549 and HepG2 cells, respectively, than cisplatin. These compounds were analyzed by interacting with the 1BNA, 4HJO, and 4ASD crystal structures in molecular docking studies.

Phytochemistry of Petroselinum crispum (Mill.) Fuss, Murraya koenigii (L.) Spreng. and Cinnamomum tamala (Buch.-Ham.) T. Nees & C. H. Eberm. and in silico studies of the role of their bioactive components against cancer

Phytochemical profiling using reliable equipment and validated methods helps us know the medicinal value of the plants. Since natural compounds have fewer side effects, they can serve as replacements for synthetic drugs that are being used in the treatment of challenging chronic diseases like cancer. The present study focuses on the bioactive phytochemical profiling of Petroselinum crispum (Mill.) Fuss, Murraya koenigii (L.) Spreng., and Cinnamomum tamala (Buch.-Ham.) T. Nees & C. H. Eberm. and in silico studies to check the anticancer potential of their bioactive components. In thin-layer chromatography (TLC) plate analysis, it was found that the methanolic extracts of plants contained the maximum number of components. Gas chromatography–mass spectrometry (GC-MS) analysis of the methanolic extracts of plants showed the presence of 22 bioactive components. High-performance thin-layer chromatography (HPTLC) analysis of the extracts of these plants showed the important chromatographic peak, apigenin. In silico studies showed the binding efficacy of selected bioactive components observed in the analysis of plant extracts. Amongst them, apigenin was found to be most effective at binding to the receptors of targeted cancer cells, viz., hepatocellular carcinoma, lung, and breast cancer. After the analysis of the study, it was arrived at the conclusion that the plants, viz., P. crispum, M. koenigii, and C. tamala, possess various bioactive components, and some of these components have anticancer potential. Therefore, in vivo and in vitro studies should be essentially conducted for the development of cancer-preventive drugs.

Synthesis and Characterization of TiO2 -CQDs Nanocomposites and Testing of Their Anticancer Potential

This work used a green approach to produce carbon quantum dots (CQDs). TiO2 nanoparticles (NPs) and TiO2–CQDs nanocomposites with different weight ratios of CQDs were organized through a facile sol-gel method. XRD showed that the anatase and rutile phases of TiO2 were polycrystalline with a tetragonal structure and that the CQDs exhibited a broad peak at (002) and a hexagonal structure. High resolution-transmission-electron microscopy revealed that the TiO2 NPs agglomerated in mostly spherical shapes and that the anatase and rutile phases of TiO2 had sizes of less than 15 and 25 nm, respectively. The CQDs had a relatively uniform diameter, a spherical shape with a highly crystalline structure, and a size below 2 nm. UV–visible spectroscopy revealed that the absorbance of the TiO2- CQDs nanocomposites increased with the increase in CQD ratio. The energy band gaps of the anatase and rutile phases were 3.07 and 2.7 eV, respectively, whereas that of CQDs was 3.14 eV. Meanwhile, the energy band gaps of the TiO2–CQDs nanocomposites decreased with the increase in CQDs ratio. The growth inhibition rates of the liver cancer HepG2 cell line and the normal cell line RD were measured after 24 hours of experience to the two TiO2 phases and TiO2–CQDs nanocomposites. The cytotoxicity test presented that the tested substances were extremely harmful to cells in cancer. Inhibition rates increased with the increase in CQDs ratio. The inhibition rate of growth in cancer cells, including the liver cancer HepG2 cell line and the normal cell line (RD), was measured for 24 hours after they were exposed to TiO2 (two phases) and TiO2-CQDs nanocomposites. The samples showed a slight effect on the normal line (RD) compared to HepG2 cancer. The highest inhibition rate was 12.11% for the CQD 0.7 sample.

Unraveling the therapeutic potential of Satureja nabateorum extract: inducing apoptosis and cell cycle arrest through p53, Bax/Bcl-2, and caspase-3 pathways in human malignant cell lines, with in silico insights

Satureja nabateorum, known as Nabatean savory is a Lamiaceae plant native to the Arabian Peninsula, specifically in the mountainous regions of Saudi Arabia. The study aims to investigate the phytochemical components of the S. nabateorum leaves (SNL) and stems (SNS) extract and to assess their antioxidant, antimicrobial, and antiproliferative properties. Methanol extracts from leaves and stems were analyzed for chemical constituents using the GC-MS technique. Antioxidant capacities were measured using hydrogen peroxide and ABTS radical-scavenging methods, and antimicrobial activity was tested against various microorganisms. Cytotoxic activity on four human malignant cell lines was assessed using MTT and flow cytometry. Molecular docking and molecular dynamics studies were conducted to understand the interactions and binding modes of the extracted compounds at a molecular level. GC-MS analysis of SNL extract revealed thymol, carvacrol, and p-cymen-8-ol as major constituents. SNS extract contained β-sitosterol, stigmasterol, lupeol, and lup-20(29)-ene-3β,28-diol. SNS extract exhibited more potent antioxidant, antimicrobial, and anticancer effects than SNL extract. The extract, SNS, exhibited potential toxicity in A549 cells with an IC50 value of 3.62 µg/mL and induced marked apoptotic effects with S phase-cell cycle arrest. SNS extract also showed higher levels of Caspase 3, Bax, p53, and the Bax/Bcl2 ratio and lower levels of Bcl-2. Molecular docking and dynamic simulation supported these findings, targeting the EGFR TK domain. The study suggests that the S. nabateorum stem extract holds promise as a potent antimicrobial, antioxidant, and anticancer agent. It provides valuable insights for considering the extract as a substitute for chemotherapy and/or protective agents.

Formulating Spray-Dried Albumin-Modified Lipid Nanoparticles Encapsulating Acyclovir for Enhanced Pulmonary Drug Delivery.

Viral pneumonia, a pressing global health issue, necessitates innovative therapeutic approaches. Acyclovir, a potent ring-opening antiviral agent with broad-spectrum activity, faces water solubility, oral bioavailability, and drug resistance challenges. The aim of this study was to increase the efficacy of acyclovir through respiratory delivery by encapsulating it within albumin-modified lipid nanoparticles and formulate it as a spray. Nanoparticles was synthesized via the reverse evaporation method; its physicochemical characteristics were rigorously evaluated, including particle size, zeta potential, morphology, encapsulation efficiency, drug loading, and release profile. Furthermore, the cytotoxicity of nanoparticles and its therapeutic potential against viral pneumonia were assessed through cellular and animal model experiments. Result s: Nanoparticles exhibited a spherical morphology, with a mean particle size of 97.48 ± 5.36 nm and a zeta potential of 30.28 ± 4.72 mv; they demonstrated high encapsulation efficiency (93.26 ± 3.27%), drug loading (11.36 ± 0.48%), and a sustained release profile of up to 92% under neutral conditions. Notably, nanoparticles showed low cytotoxicity and efficient intracellular delivery of acyclovir. In vitro studies revealed that nanoparticles significantly reduced interleukin-6 levels induced by influenza virus stimulation. In vivo, nanoparticles treatment markedly decreased mortality, attenuated the inflammatory markers interleukin-6 and tumor necrosis factor-α levels, and mitigated inflammatory lung injury in mice with viral pneumonia. In this study, albumin was modified with polyethylene glycol (PEG) containing cationic lipid nanoparticles (LN) to prepare albumin-modified lipid nanoparticles encapsulating acyclovir (ALN-Acy), which can effectively deliver Acy into tissues and cells, prolong the survival of mice, and reduce lung injury and inflammatory factors. White albumin LN can be used as efficient drug delivery carriers, and the delivery of Acy via albumin LN is expected to be a therapeutic strategy for treating inflammatory diseases.

Biofilm Demolition by [AuIII(N^N)Cl(NHC)][PF6]2 Complexes Fastened with Bipyridine and Phenanthroline Ligands; Potent Antibacterial Agents Targeting Membrane Lipid.

The development of new antibacterial drugs is essential for staying ahead of evolving antibiotic resistant bacterial (ARB) threats, ensuring effective treatment options for bacterial infections, and protecting public health. Herein, we successfully designed and synthesized two novel gold(III)- NHC complexes, [Au(1)(bpy)Cl][PF6]2 (2) and [Au(1)(phen)Cl][PF6]2 (3) based on the proligand pyridyl[1,2-a]{2-pyridylimidazol}-3-ylidene hexafluorophosphate (1•HPF6) [bpy= 2,2'-bipyridine; phen= 1,10-phenanthroline]. The synthesized complexes were characterized spectroscopically; their geometries and structural arrangements were confirmed by single crystal XRD analysis. Complexes 2 and 3 showed photoluminescence properties at room temperature and the time-resolved fluorescence decay confirmed the fluorescence lifetimes of 0.54 and 0.62 ns respectively; which were used to demonstrate their direct interaction with bacterial cells. Among the two complexes, complex 3 was found to be more potent against the bacterial strains (Staphylococcus aureus, Gram-positive and Pseudomonas aeruginosa, Gram-negative bacteria) with the MIC values of 8 µg.mL-1 and 16 µg.mL-1 respectively. Studies revealed the binding of the complexes with the fundamental phospholipids present in the cell membrane of bacteria, which was found to be the leading cause of bacterial cell death. Cytotoxicity was evaluated using an MTT assay on 293T cell lines; emphasizing the potential therapeutic uses of the Au(III)-NHC complexes to control bacterial infections.

Current Insights into Therapeutic Potential of Terpenoids as Anticancer Agents.

Cancer is regarded as one of the main causes of death globally. Future predictions indicate that the death rate from cancer will keep rising, which may reach 11.4 million in 2030. Carcinogenesis refers to the phenomenon of transforming a normal cell into a cancer cell. Cancer is characterized by unregulated and uncontrolled cell division due to alterations at the molecular and genetic levels. Gene mutations can speed up the rate of cell division, which leads to cancer. Metastasis entails the dissemination of cancer cells from the primary site to distant regions of the body via the circulatory or lymphatic systems. This review is mainly focusing on the anticancer properties of terpenoids. In the case of human beings, several types of cancers can be treated clinically based on the form and phase of the cancer. So, there are different types of treatment regimens available for the management of cancer, such as immunotherapy, hormonal therapy, radiation therapy, and chemotherapy. Several problems are associated with cancer therapy, including chemoresistance, severe toxicity, relapse, and metastasis. To minimize these complications, natural products like terpenoids seem to be beneficial for the effective management of cancer. Experimental results revealed that the anticancer potential of terpenoids is due to activation of apoptosis and stimulation of cell cycle arrest. Some of the terpenoids exhibit anticancer effects by inhibiting angiogenesis and metastasis via the regulation of several signaling pathways intracellularly. Certain terpenoids have been shown to work in concert with anticancer medications (doxorubicin, cisplatin, paclitaxel, and 5-fluorouracil) to provide synergistic effects. These terpenoids have also been shown to be effective against cancer cells that are resistant to several drug therapies. The current study will focus on signaling pathways and mode of action of several types of terpenoids as anticancer agents. Further, it will provide insights into the ongoing clinical trials and prospective pathways for the advancement of terpenoids as possible anti-cancer agents.

Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR-ABL-Positive Leukemia.

SOS1 is an essential guanine nucleotide exchange factor for RAS that also plays a critical role in the activation of the small GTPase RAC mediated by BCR-ABL in leukemogenesis. Despite this, small molecule inhibitors targeting SOS1 have shown limited efficacy in clinical trials for KRAS mutant cancers, and their potential as a therapeutic approach for chronic myeloid leukemia (CML) remains largely unexplored. In this study, we developed a potent SOS1 PROTAC SIAIS562055, which was designed by connecting a CRBN ligand to an analogue of the SOS1 inhibitor BI-3406. SIAIS562055 exhibited sustained degradation of SOS1 and inhibition of downstream ERK pathways, resulting in superior anti-proliferative activity compared to small molecule inhibitors. SIAIS562055 also potentiated the activity of both KRAS inhibitors in KRAS-mutant cancers and ABL inhibitors in BCR-ABL+ CML. In KRAS-mutant xenografts, SIAIS562055 displayed promising antitumor potency as a monotherapy and enhanced ERK inhibition and tumor regression when combined with KRAS inhibitors, overcoming acquired resistance. In CML cells, SIAIS562055 promoted the active uptake of BCR-ABL inhibitors by upregulating the carnitine/organic cation transporter SLC22A4. SIAIS562055 and BCR-ABL inhibitors synergistically enhanced inhibition of ABL phosphorylation and downstream signaling, demonstrating robust antitumor activities in both mouse xenografts and primary CML patient samples. In summary, this study suggests that PROTAC-mediated SOS1 degradation represents an effective therapeutic strategy for treating not only KRAS-mutant cancers but also BCR-ABL-harboring leukemia.

A Dual Approach by Nanostructured α-Mangostin-Copper Oxide Complexes Against Dental Pathogen Biofilms and Oral Cancer via Apoptosis Gene Modulation.

The development of effective treatments for dental pathogens and oral cancer remains a significant challenge. Copper oxide nanoparticles (CuO NPs) are recognized for their strong antimicrobial properties, attributed to the synthesis of oxygen-dependent radicals. α-Mangostin (MG), a natural xanthone from mangosteen fruit, is well-known for its antioxidant, antimicrobial, and anticancer potential. Antioxidant activity was assessed using superoxide anion and hydroxyl radical anion. The anticancer potential was evaluated by examining apoptosis induction in oral cancer cell lines, focusing on the expression of key apoptotic markers such as Caspase-3, Caspase-8, and FasL. Molecular docking simulations were performed to understand the interaction between MG and biofilm receptors. The CuO-MG NPs evidenced significant antimicrobial efficacy against all tested oral pathogens, with enhanced efficacy attributed to the combined effects of CuO-induced oxidative stress and the antimicrobial properties of MG. Molecular docking studies revealed strong binding affinities of MG to key biofilm receptors, disrupting pathogen adhesion and biofilm formation. CuO-MG NPs demonstrate synergistic antimicrobial, antioxidant, and anticancer properties, offering a potential approach for the management of oral infections and oral cancer. Further preclinical and clinical studies are recommended to ensure their safety and stability in medical applications.

Novel Strategies for Synthesis and Assessment of Dextran Conjugated 9Z,11E Linoleic Acid on Cancer Cell Lines Viability via Wnt/Beta‐Catenin Signaling Pathway and Apoptosis

AbstractConjugated linoleic acid (CLA) is one of the positional and structural isomers of linoleic acid. Ninety percent of the CLA contained in natural foods is the cis‐9(9Z), trans‐11(11E) isomer. CLA also has anti‐carcinogenic, anti‐adipogenic, and anti‐inflammatory properties. Limited studies aim to elucidate the impact of 9Z,11E‐CLA on Wnt/beta‐catenin signaling.In this study, we have selected MDA‐MB‐231, T98G, and SAOS‐2 cell lines of various cancer origins and investigate the impact of dextran conjugated 9Z,11E CLA (Dex‐9Z,11E‐CLA) using cell proliferation assay and immunocytochemical methods. Cytotoxic effects of Dex conjugated 9Z,11E CLA are assessed with the MTT method. It analyzed Wnt/beta‐catenin signaling changes using target molecule beta‐catenin, Dickkopf‐1 (Dkk‐1) as a negative regulator, and active caspase3 (CC3) as an apoptotic marker.Dex‐9Z,11E‐CLA is shown to suppress cell viability in three different types of cancer cells, and the most effective concentration is 200 µm. 9Z,11E‐CLA and Dex‐9Z,11E‐CLA affect the Wnt/beta‐catenin signaling pathway negatively in all cell lines. Beta‐catenin expression is decreased, Dkk‐1 expression is increased, and CC3 positivity is increased significantly compared to the control group. In conclusion, the data suggest that Dex‐9Z,11E‐CLA suppresses cell viability and causes apoptosis in cells via the Wnt/beta‐catenin signaling pathway. Lastly, Dex‐9Z,11E‐CLA harbors novel anticancer potential and exhibits uncontrolled activation of Wnt/beta‐catenin signaling.

Hepatopulmonary syndrome associated with long-term use of ado-trastuzumab emtansine (T-DM1) for treatment of HER2-positive metastatic breast cancer - a case report and series

BackgroundThe advent of antibody-drug conjugates (ADCs) represents a landmark advance in cancer therapy, permitting targeted delivery of a potent cytotoxic agent to tumor cells with minimal damage to surrounding cells. Although ADCs can induce sustained therapeutic responses in heavily pretreated patients, they can also cause significant toxicity and thus require careful monitoring. The prototype ADC, ado-trastuzumab emtansine (T-DM1) is comprised of a humanized, monoclonal human epidermal growth factor receptor 2 (HER2)-directed antibody, trastuzumab, linked to the cytotoxic agent, DM1, and is used for the treatment of early-stage and advanced HER2-positive breast cancer. Liver toxicities, including transaminitis and nodular regenerative hyperplasia resulting in portal hypertension have been described. We report a case series of four patients who developed hepatopulmonary syndrome (HPS) during treatment with T-DM1. HPS is characterized by hypoxemia, portal hypertension, and intrapulmonary shunting, and it can be associated with severe hypoxic respiratory failure. HPS secondary to noncirrhotic portal hypertension occurring with long-term exposure to T-DM1 has not previously been reported.Case series presentationFour patients who received T-DM1 in our institutional cohort (n=230) developed HPS, which can be associated with severe hypoxic respiratory failure. Each patient diagnosed with HPS received >50 doses of T-DM1. Only one patient at diagnosis had resting hypoxia, while the other three patients became hypoxic with exertion only. Discontinuation of T-DM1 led to clinical improvement in hypoxia in three of the four patients. The spectrum of liver injury that occurs with long-term use of T-DM1 remains incompletely defined.ConclusionsAs T-DM1 is approved for use in the management of early-stage operable and advanced breast cancer, awareness of HPS as a potential complication of long-term administration of T-DM1 is necessary. The emergence of dyspnea alone or combined with low oxygen saturation and signs of hypoxemia (clubbing or elevated hemoglobin) should raise clinical suspicion and prompt evaluation for HPS. Cancer care team members should be vigilant regarding the potential for new and serious side effects associated with novel targeted therapies, which may emerge years beyond initial regulatory approval.

Eco-friendly Synthesis of Gold Nanoparticles of Methanolic Extract of Bauhinia vahlii Leaves and Evaluation of Tyrosinase Inhibitory Activity

Background: The green synthesis of gold nanoparticles (AuNPs) using natural materials has gained significant attention in recent years due to their eco-friendliness and potential applications in various fields. Methods: The present study aimed at the green synthesis and anti-hyperpigmentation potential of gold nanoparticles (AuNPs) using a methanolic extract of Bauhinia vahlii. Furthermore, the green synthesis of the AuNPs was confirmed by UV-visible, FT-IR, XRD, and EMDEX analysis. The size and surface topological significance of green synthesized AuNPs were evaluated through Scanning Electron Microscope and Field Emission Scanning Electron Microscopy. Results: The size of the synthesized AuNPs was found to be in the range of 100-1000 nm. The tyrosinase inhibitory activity of AuNPs was evaluated through the mushroom tyrosinase inhibitory assay method. The tyrosinase inhibitory activities of crude extract, AuNPs, and Kojic acid were found to be 98.7 ±0.7, 75±1.3 and 41±1.1 μg/ml, respectively. Conclusion: Hence, green synthesized AuNPs of B. vahlii leaf extract may be used as a potent antihyperpigmentation agent in the market of nano cosmeceuticals.

Exploring the anticancer potential of Lasia spinosa rhizomes: insights from molecular docking and DFT investigations on chlorogenic acid and beyond

Lasia spinosa (L.) Thwaites rhizomes (LSR), historically utilised in traditional medicine for various health sufferings, including cancer, represent an intriguing yet underexplored reservoir of bioactive constituents. Our study focused on exploring the anticancer potential of LSR and its phytoconstituents. The methanol extract of LSR exhibited significant cytotoxicity against various cancer cell lines compared to other extracts. The fractionation of methanol extract resulted in the isolation of chlorogenic acid (CA), oleanolic acid, β-amyrin, and lyonoresinol. Molecular docking analysis of these isolated compounds targeted at the active sites of CDK-2, VEGFR-2, and ToP-2A enzymes revealed the superior docking score of CA compared to the other constituents. Additionally, density functional theory studies indicated the strong electrophilic nature of CA and its potential for robust enzyme binding interactions. Subsequent MTT assays focusing on CA exhibited significant activity against all tested cell lines, with IC50 values ranging from 21.56 to 72.60 μg/ml, comparable to quercetin.

Thiazolidinedione-Conjugated Lupeol Derivatives as Potent Anticancer Agents Through a Mitochondria-Mediated Apoptotic Pathway.

To improve the potential of lupeol against cancer cells, a privileged structure, thiazolidinedione, was introduced into its C-3 hydroxy group with ester, piperazine-carbamate, or ethylenediamine as a linker, and three series of thiazolidinedione-conjugated compounds (6a-i, 9a-i, and 12a-i) were prepared. The target compounds were evaluated for their cytotoxic activities against human lung cancer A549, human breast cancer MCF-7, human hepatocarcinoma HepG2, and human hepatic LO2 cell lines, and the results revealed that most of the compounds displayed improved potency over lupeol. Compound 12i exhibited significant activity against the HepG2 cell line, with an IC50 value of 4.40 μM, which is 9.9-fold more potent than lupeol (IC50 = 43.62 μM). Mechanistic studies suggested that 12i could induce HepG2 cell apoptosis, as evidenced by AO/EB staining and annexin V-FITC/propidium iodide dual staining assays. Western blot analysis suggested that compound 12i can upregulate Bax expression, downregulate Bcl-2 expression, and activate the mitochondria-mediated apoptotic pathway. Collectively, compound 12i is worthy of further investigation to support the discovery of effective agents against cancer.

Immunomodulatory Effects of Citrus Species Ethanol Extracts on Cellular Immune Responses in Wistar Rats and Mice

Currenty, Citrus reticulata has been found to modulate RAW 264.7 macrophage cell line. In the present study, the immunomodulatory effects of Citrus species peel extracts, including Citrus microcarpa, C. limon L., C. sinensis L. and C. hystrix were investigated on cellular immune responses in Wistar rats and mice. Mice were treated with ethanol extracts of Citrus species orally at dosages of 25, 50 and 100 mg/kg bw for 7 days. The phagocytosis activity of the extracts was examined using the carbon clearance method. Meanwhile, oral administration of Citrus species ethanol extracts at dosages of 17.5, 35 and 70 mg/kg bw was administered to Wistar rats to assess the effect of extracts on the delayed-type hypersensitivity (DTH) response using paw edema-method. Thin Layer Chromatography (TLC)-densitometry analysis was also performed. In both animal models, all extracts enhanced the cellular immune responses. Amongst the samples, C. sinensis, at the dose of 100 mg/kg bw in mice and 70 mg/kb bw in rats, demonstrated the highest stimulation on phagocytosis activity and DTH response, respectively. Except C. microcarpa, rutin was found in all Citrus species. The results indicate that Citrus species, particularly C. sinensis, have the potential to be developed into a potent immunostimulatory agent. HIGHLIGHTS The immunomodulatory effects Citrus species were investigated using mice and rats as animal models. Citrus microcarpa, C. limon, C. sinensis L. and C. hystrix were able to stimulate phagocytosis in mice and delayed-type hypersensitivity response in rats. Citrus sinensis demonstrated the highest stimulation on phagocytosis activity and delayed-type hypersensitivity response. Rutin was found in all Citrus species, except in microcarpa peels extract. GRAPHICAL ABSTRACT

Different Doxorubicin Sensitivity Across Various Human Cancer Cell Lines

Doxorubicin (Dox) is a highly potent chemotherapeutic agent, approved by FDA since 1974, for treating a broad spectrum of cancers. However, development of severe side effects and drug resistance are main issues that limit the clinical use of Dox. Herein, we aimed to investigate the sensitivity of Dox in a variety of human cancer cell lines. Eleven cell lines were tested in this study including 2 hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh7), 4 bladder cancer (BlCa) cell lines (UMUC-3, VMCUB-1, TCCSUP and BFTC-905), a lung cancer cell line (A549), a cervical carcinoma cell line (HeLa), a breast cancer cell line (MCF-7), a skin melanoma cell line (M21) and a noncancer human kidney cell line (HK-2). The MTT assay was employed for the determination of cytotoxicity. Cells were treated with various concentrations of Dox for 24 h. The half-maximal inhibitory concentration (IC50) of Dox was calculated to compare the Dox sensitivity among tested cell lines. The result showed that IC50 of Dox in HepG2, Huh7, UMUC-3, VMCUB-1, TCCSUP, BFTC-905, A549, HeLa, MCF-7, M21 and HK-2 cells were 12.2, > 20, 5.1, > 20, 12.6, 2.3, > 20, 2.9, 2.5, 2.8 and > 20 mM, respectively. BFTC-905 had the lowest IC50 value, therefore, it was the most sensitive to Dox. In contrast, Huh7, VMCUB-1 and A549 cells were resistant to Dox with IC50 values > 20 mM. Conclusions, we demonstrated that different human malignant cell lines had different sensitivity to Dox. BFTC-905 BlCa cell line had the highest sensitivity to Dox. Huh7, VMCUB-1 and A549 cell lines were resistant to Dox. Perhaps, the different Dox sensitivity in different cell lines was due to the different acquisition of Dox resistance mechanisms. Huh7, VMCUB-1 and A549 cell lines could be suitable cell models to investigate the molecular mechanism of Dox resistance in different cancers. HIGHLIGHTS Different types of cancer cell lines exhibited different sensitivity to doxorubicin. BFTC-905, MCF-7 and M21 cell lines were sensitive to doxorubicin. HepG2, UMUC-3, TCCSUP and HeLa cells were moderately sensitive to doxorubicin. Huh7, VMCUB-1, A549 and HK-2 cells were resistant to doxorubicin. Huh7, VMCUB-1 and A549 cell lines could be suitable cell models for investigating the molecular pathways of Dox resistance in different types of cancers. GRAPHICAL ABSTRACT