Cytotoxic Potential Research Articles

Management of nausea and vomiting induced by antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are an emerging class of anticancer therapy that combines the specificity and long circulation half-life of monoclonal antibodies with the cytotoxic potency of the payload connected through a chemical linker. The optimal management of toxicities is crucial for improving quality of life in patients undergoing ADCs and for avoiding improper dose reductions or discontinuations. This article focuses on the characteristics and management of nausea and vomiting (NV) induced by three ADCs: trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), and datopotamab deruxtecan (Dato-DXd). We summarize the proposed mechanism of NV, clinical study data on NV, and recommendations from clinical guidelines. We also discuss three prospective studies evaluating prophylactic antiemetic therapy in patients receiving T-DXd, along with future perspectives.

Optimization, characterization and biosafety of oregano, rosemary and mint oil mixture against Penicillium digitatum in citrus using L-optimal mixture design

The increasing demand for natural alternatives to synthetic fungicides has prompted research into natural products like essential oils for postharvest disease management. This study investigated the antifungal, antioxidant, cytotoxic, and genotoxic potential of essential oil mixtures derived from oregano, rosemary, and mint against Penicillium digitatum, the predominant fungal pathogen causing green mold in orange fruits. P. digitatum NPAGRASU 2024 was isolated and identified as the most abundant species (60.2%) from infected oranges. It was deposited in GenBank with gene accession number PP930644 and deposited in MIRCEN culture collection as EMCC 358874. The antimicrobial activity of individual essential oils was evaluated, with oregano exhibiting the highest antifungal activity (inhibition zone diameter of 4.2 cm) against P. digitatum. L-optimal mixture design of response surface methodology (RSM) optimization revealed a highly effective mixture (Run 8) comprising 46.26% oregano and 53.74% rosemary, with a 99.65% actual growth reduction. The oregano oil demonstrated potent antioxidant activity, reaching approximately 75% DPPH radical scavenging at 3.125 mg/mL. Cytotoxicity assessment using the MTT assay showed morphological changes and reduced cell viability in liver cells treated with the PEOs mixture at 300 µg/mL. However, the optimized mixture did not induce significant chromosomal aberrations compared to the control, suggesting minimal genotoxic effects. In vivo, evaluation on oranges revealed 60% inhibition of green mold by the 1% (v/v) optimized mixture for 7 days. Histological analysis indicated low toxicity to the liver at the highest tested concentration (1% mixture). GC-MS analysis identified major compounds like cavarcol, caryophyllene, eucalyptol, phenols and levomenthol in oregano oil, contributing to its bioactivities. This study demonstrates the potential of optimized essential oil mixtures as effective and eco-friendly alternatives for postharvest disease control.

Design of ROS-Triggered Sesquiterpene Lactone SC Prodrugs as TrxR1 Covalent Inhibitors for the Treatment of Non-Small Cell Lung Cancer.

Thioredoxin reductase 1 (TrxR1) is an important therapeutic target for nonsmall cell lung cancer (NSCLC) treatment due to its overexpression in NSCLC cells. In this work, to address the deficiency that sesquiterpene lactone containing α-methylene-γ-lactone moiety was rapidly metabolized by endogenous nucleophiles, series of novel thioether derivatives were designed and synthesized based on a reactive oxygen species (ROS)-triggered prodrug strategy. Among them, prodrug 5u exhibited potent cytotoxicity against NSCLC cells and better release rates in response to ROS. The active compound 6a released from 5u covalently binds to Cys475 and Sec498 sites on TrxR1, resulting in inhibition on TrxR1 activity, which led to redox homeostasis disorder, and caused apoptosis and ferroptosis. Moreover, prodrug 5u exhibited significant antitumor efficiency in nude mice and NSCLC organoids. Our results deliver ROS-triggered prodrug 5u as a novel TrxR1 inhibitor for the treatment of NSCLC and provide a promising strategy of ROS-activated prodrug for covalent compounds in cancer therapy.

Lewis Acid Catalyzed Regioselective Substitution of 2-Indolylmethanols with Pyrroles

AbstractA Lewis acid catalyzed regioselective C2′-electrophilic substitution of 2-indolylmethanols with pyrroles has been established, which affords indole-based tetraarylmethanes in overall high yields (up to 99%) with excellent regioselectivities. Moreover, such indole-based tetraarylmethanes exhibit potent cytotoxicity against HepG2 cancer cells, which demonstrates their potential applications in medicinal chemistry. This reaction not only represents the regioselective C2′-electrophilic substitution of 2-indolylmethanols with aryl nucleophiles (Ar-Nu), but also provides a new strategy for the synthesis of biologically important tetraarylmethanes.

In silico molecular docking and in vitro analysis of atomoxetine

Although atomoxetine, a selective norepinephrine reuptake inhibitor, is widely used in the treatment of attention-deficit/hyperactivity disorder (ADHD), there is limited data on its cytogenetic effects. This study aimed to investigate the cytotoxicity and genotoxicity of atomoxetine in vivo and silico. Chromosome aberration and micronucleus assays were used to analyze the genotoxic effect of atomoxetine in human peripheral blood lymphocytes under culture conditions. The mitotic index was assessed for cytotoxic potential. For the docking analysis, DNA receptor (1BNA) was prepared with ChimeraX, and the Atomoxetine molecule was optimized by Avogadro2.0 software. In silico molecular docking analysis was carried out utilizing SwissDock online platform. The results obtained were visualized using ChimeraX and Pymol software. Atomoxetine doses of 9.6 µg/mL (equal to about 1.2 mg/kg as a maintenance dose), 14.4 µg/mL (equal about to 1.8 mg/kg as the highest dose systematically tested), 48.0 µg/mL (equal about to 6 mg/kg as five times the maintenance dose) and 96.0 µg/mL (equal about to 12 mg/kg as ten times the maintenance dose) were analyzed. The findings clearly indicate that atomoxetine has no genotoxic effect at the therapeutic dose. However, we observed genotoxic effects at 48.0 and 96.0 µg/mL doses. No strong binding affinity occurs in silico analyses. As one of the initial inquiries into the in silico and in vivo appraisal of atomoxetine’s genotoxic impacts, the research has established that atomoxetine does not significantly affect the frequency of chromosomal damage or micronucleus formation. Genotoxic effects should be kept in mind at doses above clinical practice.

Ferrocene Derivatives as Histone Deacetylase Inhibitors: Synthesis and Biological Evaluation

Ferrocene is an organometallic compound that has attracted considerable scientific interest due to its unique properties, including low toxicity, excellent stability in aqueous and aerobic media, and high lipophilicity, which enhances membrane permeability. The ferrocene moiety has been effectively used as a bioisostere of phenyl rings and heteroaromatic groups in the structures of approved tyrosine kinase inhibitors and histone deacetylase inhibitors (HDACis). HDACis exert their cytotoxic effects by blocking cyclin/CDK complexes, causing cell cycle arrest, inducing apoptosis, inhibiting angiogenesis, and through non-histone-directed mechanisms. This mini-review summarizes the synthesis and biological evaluation of small libraries of compounds in which a ferrocenyl moiety is incorporated into the structure of suberoylanilide hydroxamic acid (SAHA) and a number of analogues. The influence of the organometallic function on the antiproliferative effect is investigated. Both docking analysis and in vitro studies confirm that the ferrocenyl-modified HDACis exhibit potent cytotoxicity and strong inhibitory activity against the various enzyme isoforms.

Modeling the response to interleukin-21 to inform natural killer cell immunotherapy.

Natural killer (NK) cells are emerging agents for cancer therapy. Several different cytokines are used to generate NK cells for adoptive immunotherapy including interleukin (IL)-2, IL-12, IL-15 and IL-18 in solution, and membrane-bound IL-21. These cytokines drive NK cell activation through the integration of signal transducers and activators of transcription (STAT) and nuclear factor-kappa B (NF-κB) pathways, which overlap and synergize, making it challenging to predict optimal cytokine combinations for both proliferation and cytotoxicity. We integrated functional assays for NK cells cultured in a variety of cytokine combinations with mathematical modeling using feature selection and mechanistic regression models. Our regression model successfully predicts NK cell proliferation for different cytokine combinations and indicates synergy of activated STATs and NF-κB transcription factors between priming and post-priming phases. The use of IL-21 in solution in the priming of NK cell culture resulted in an improved NK cell proliferation, without compromising cytotoxicity potential or interferon gamma secretion against hepatocellular carcinoma cell lines. Our work provides an integrative framework for interrogating NK cell proliferation and activation for cancer immunotherapy.

Biomonitoring of the Paraopeba river: Cytotoxic, genotoxic and metal concentration analysis three years after the Brumadinho dam rupture - Minas Gerais, Brazil.

The rupture of Vale S.A. mining tailings dam in Brumadinho, Brazil, in January 2019 had significant environmental impacts on the Paraopeba River basin. Additionally, severe floods in early 2022 contributed to the transport of particles in the river. This study aimed to evaluate the cytotoxic and genotoxic potential of Paraopeba River water. Thus, the Allium cepa test system was applied, along with physicochemical analyses, flow cytometry, and metal concentration, comparing the results between the rainy and dry seasons three years after the dam rupture. The tests were conducted on water samples collected during three periods: January 2022, July 2022, and January 2023, at five points along the river and its tributaries. Allium cepa seeds were exposed to the collected water samples, as well as negative (water) and positive (trifluralin) controls. Cytotoxicity was evaluated using the mitotic index and flow cytometry, and genotoxicity by the chromosomal alterations index. The analysis of metals and physicochemical parameters revealed that most values complied with current regulations. However, there were exceptions, with ammonia levels exceeding the permitted limits at all points in the three collections. High levels of aluminum, iron and nitrite were found at most points, before and after the dam collapse, mainly during the rainy season. This indicates the impact of rainfall on water quality, which increases the transport of contaminating particles, probably resulting from human activities and the high concentration of nitrogen compounds released into the Paraopeba River. The results of the bioassay suggest a relatively low cytotoxic and genotoxic potential of the samples evaluated. However, this study highlights the continuous contamination of the river by unidentified anthropogenic factors, requiring continuous monitoring and analysis to track the evolution of water quality and its environmental effects.

Comparative Phytochemistry of Polyacetylenes of the Genus Artemisia (Asteraceae): Compounds with High Biological Activities and Chemotaxonomic Significance

In spite of the many chemical reports on polyacetylenes of the genus Artemisia, combined conclusions regarding their distribution and biological functions are widely missing. The aim of the present review was to arrange the diversity of polyacetylenes in the genus following biogenetic aspects and group them together into characteristic structural types. The co-occurrence of the dehydrofalcarinol type with the aromatic capillen-isocoumarin type represents a characteristic biogenetic trend, clearly segregating species of the subgenus Dracunculus from those of the subgenera Artemisia and Absinthium, distinguished by the spiroketal enol ether and/or linear triyne type. Various accumulation trends toward specific structures additionally contribute to a more natural species grouping within the subgenera. Biological activities were reported for all four structural types, ranging from antifungal, insecticidal, nematicidal, and cytotoxic properties to allelopathic effects. Of particular interest were their remarkable cytotoxic potencies, from which the very high values of dehydrofalcarin-3,8-diol may be associated with the pronounced affinity of this type to form extremely stable bonds to proteins acting in signaling pathways. The aromatic acetylene capillin inhibited the viability of various tumor cells in a dose- and time-dependent manner. Its potent apoptosis-inducing activity was induced via the mitochondrial pathway. A group of spiroketal enol ethers was identified as inhibitors of PMA-induced superoxide generation. Among them, the epoxide of the isovalerate ester exhibited the highest potency. The ecological impact of acetylene formation was made apparent by the allelopathic effects of DME of the linear triyne type, and the aromatic capillen by inhibiting seed germination and growth of widespread weeds.

Synthesis, cytotoxicity, apoptosis-inducing activity and molecular docking studies of novel isatin-podophyllotoxin hybrids.

Podophyllotoxin, along with its numerous derivatives and related compounds, is well known for its broad-spectrum pharmacological activity, especially for anticancer potential. In this study, several isatin-podophyllotoxin hybrid compounds were successfully synthesized with good yields through microwave-prompted three-component reactions of 2-amino-1,4-naphthoquinone, various substituted isatins, and tetronic acid. Their cytotoxicity was assessed against four types of human cancer cell lines, HepG2 (hepatoma carcinoma), MCF7 (breast cancer), A549 (non-small lung cancer), and KB (epidermoid carcinoma), alongside nontumorigenic HEK-293 human embryonic kidney cells. Among 14 compounds screened, 7f possessed the strongest cytotoxicity to KB and A549 cell lines, with IC50 values of 1.99 ± 0.22 and 0.90 ± 0.09 μM, respectively. Further studies revealed that product 7f could arrest the cell cycle of A549 cells at S phase and induce apoptosis of A549 cells. This compound was examined for its binding ability against cyclin-dependent kinases (CDKs) and procaspase/caspase systems. The results indicated that 7f exhibited significant interactions with the residues of the ATP binding sites of CDK2/cyclin A and CDK5/p25 and also activated procaspase 6 through stable zinc chelation. Additionally, physicochemical and pharmacokinetic properties related to drug-likeness, in parallel with toxicity, were computationally assessed to identify the main issues that need to be addressed in structural optimization. Taken together, compound 7f was identified as a potent cytotoxic agent that could be considered for anticancer drug discovery and development.

ALTERNATIVE BIOLOGICAL MODELS FOR EVALUATION OF THE TOXIC, GENOTOXIC AND MUTAGENIC POTENTIAL OF Ectatomma brunneum Smith VENOM.

The venom of Ectatomma brunneum is considered promising for drugs development. Therefore, it is important to evaluate its toxic potential and genetic instability using biological assays. To this end, toxicity assays were performed with Artemia salina, cytotoxicity and genotoxicity with Allium cepa and mutagenicity with Ames. The results indicated toxicity to A. salina, and no cytotoxic, genotoxic or mutagenic potential at concentrations equal to or lower than 500 μg/mL for the other tests.

Enhancing Tumor Cell Affinity and Inhibiting Growth With Albumin‐Coated Crosslinked Chitosan Nanoparticle Micelles

ABSTRACTChitosan (CS)‐based drug delivery systems often face challenges in obtaining clinical approval. Enhancing the binding affinity of CS‐based carriers to target cells, such as tumor cells, is crucial for their translation from bench to bedside. Strategies like crosslinking (NHS‐disulfide‐NHS) and utilizing materials like albumin have proven effective in strengthening interactions between CS‐based nanoparticles and tumor cells, thereby enhancing cellular uptake (cellular avidity). This study presents a novel approach using crosslinked CS nanoparticles loaded with doxorubicin, featuring reduction‐responsive drug release and albumin coating. The albumin‐coated crosslinked chitosan (ACCC) was assembled via reaction between amino of CS/albumin and NHS‐disulfide‐NHS. The resulting ACCC nanoparticle micelles demonstrate enhanced stability of the micelles. The hybrid crosslinked network ensures stability while providing ample space for drug loading and achieves reduction‐responsive drug release through disulfide bond crosslinking. Moreover, the proposed system possesses excellent biocompatibility. Compared to uncoated crosslinked chitosan nanoparticle micelles, ACCC nanoparticle micelles exhibit potent cytotoxicity against tumor cells, particularly in reducing environment. Fluorescence imaging and flow cytometry analyses confirm the enhanced cellular affinity conferred by albumin coating. These findings underscore the potential of ACCC nanoparticles in improving tumor cell adhesion and anti‐tumor efficacy, thus offering promising prospects for translational medicine in CS‐based drug delivery.

Cyclic Lipopeptides as Selective Anticancer Agents: In vitro Efficacy on B16F10 Mouse Melanoma Cells.

In this study, 25 synthetic cyclic lipopeptides (CLPs) were investigated for their anticancer potential against mouse melanoma (B16F10) cells, human prostate cancer (PC-3), human colorectal adenocarcinoma (HT-29) and mouse embryonic fibroblast (NIH3T3) cells. The cytotoxic activity of investigated compounds was evaluated using MTT and CV assays. In order to examine the mechanism of action of the most potent compound cell cycle analysis, apoptosis assay, caspase activity, CFSE and DHR staining, DAF-FM, autophagy and immunocytochemistry caspase-3 assays were performed. During the fast screening, compound 9, was identified as prospective active CLP against B16F10 cell line at 10 μM concentration. MTT and CV assays exhibited at least four times higher cytotoxic potential of 9 (IC50 = 8.4±1.3 μM, MTT; 10.6±1.1 μM, CV) in comparison to control drug natural occurring CLP surfactin (IC50 = 50.3±0.6 μM, MTT; 40.4±0.3 μM, CV). The use of flow cytometry analysis confirmed that apoptosis was involved in the death of B16F10 cells after treatment with 9, as demonstrated also by DAPI staining. Caspase activity could be detected during cell death (ApoStat assay, immunocytochemistry caspase-3 assay). Compound 9 provokes enhancement of nitric oxide (NO) production in B16F10 cells but does not trigger ROS/RNS generation or autophagy. The study highlights synthetic compound 9 superior tumor-specificity and potential as an anticancer agent compared to surfactin and cisplatin. These findings could guide the development of more selective and less harmful macrocyclic lipopeptides for cancer therapy.

Oncology. Antibody-drug conjugates : a challenging innovation

New therapeutic agents in oncology are emerging rapidly, both in terms of the number of approved drugs and the technological and biological innovation of new treatments. Antibody-drug conjugates (ADC) offer a promising cancer therapy by specifically targeting tumor cells. ADC are composed of a monoclonal antibody recognizing the tumor cell via specific antigens, coupled with a potent cytotoxic agent that resembles classical chemotherapy. This mechanism of action aims to deliver the cytotoxic agent directly to the tumor cell and spare healthy cells. However, important toxicities have been reported. On the one hand, these toxicities are related to the cytotoxic agents that, once delivered locally, spread to other parts of the body. On the other hand, there are specific toxicities associated with these ADC, which we address in this article.

Exploring CAR-PBMCs: A Novel Strategy Against EGFR-Positive Tumor Cells

Background: Chimeric antigen receptor (CAR) T cell therapy has shown significant promise in treating hematological malignancies, yet its application in solid tumors, particularly those expressing the epidermal growth factor receptor (EGFR), remains limited. This study investigates the potential of CAR-engineered peripheral blood mononuclear cells (PBMCs) as a novel adoptive cell therapy against EGFR-positive cancers. Methods: Lentiviral transduction at an MOI of 50 was performed to generate specific anti-EGFR second generation CAR-effector cells. The transduced PBMCs were stimulated with cytokines and CD3/CD28 beads to enhance their proliferation and activation. Flow cytometric and real-time cell analysis were performed at various effector-to-target ratios to explore the cytotoxic potential of CAR-PBMCs. Results: CAR-PBMCs exhibited improved targeting and cytotoxicity against EGFR-positive cancer cell lines MDA-MB-468 and SK-BR-3, compared to untransduced controls, with unsignificant effects on allogeneic PBMCs. Conclusion: CAR-PBMCs hold considerable potential as a therapeutic strategy for EGFR-positive solid tumors, warranting further clinical investigation.

A 37-Color Spectral Flow Cytometric Panel to Assess Transcription Factors and Chemokine Receptors in Human Intestinal Lymphoid Cells.

We have developed a 37-color spectral flow cytometry panel to assess the phenotypical differentiation of innate and adaptive immune lymphoid subsets within human intestinal tissue. In addition to lineage markers for identifying innate lymphoid cells (ILC), TCRγδ, MAIT (mucosal-associated invariant T), natural killer (NK), CD4+ and CD8+ T cells, we incorporated markers of differentiation and activation (CD45RA, CD45RO, CD25, CD27, CD38, CD39, CD69, CD103, CD127, CD161, HLA-DR, CTLA-4 [CD152]), alongside transcription factors (Bcl-6, FoxP3, GATA-3, Helios, T-bet, PU.1 and RORγt) and chemokine receptors (CCR4, CCR6, CCR7, CXCR3, and CXCR5). Additionally, Granzyme B and Ki-67 were included to assess cytotoxicity and proliferation potential of the different subsets. This panel is currently used for in-depth immunophenotyping in endoscopic biopsies and peripheral blood mononuclear cells (PBMC) from inflammatory bowel disease (IBD) patients. Distinguished from other OMIP papers, the comprehensive detection of both transcription factors and chemokine receptors facilitates the efficient assessment of several subsets, particularly CD4+ T helper cells, and its potential application extends to both tissue and circulation.

Assessment of pharmacological properties of root extracts from <i>Ficus capensis</i>

Evaluation of pharmacological properties of root extracts from fig tree was conducted using different organic solvents in the extraction process. Six (6) samples were prepared for experimental assessment of their cytotoxicity, brine shrimp lethality, antioxidant, total-antioxidant and antibacterial activities using conventional methods with slight modifications. Results obtained from the analyses revealed their potency against bacterial strains, brine shrimp larvae and radical/electron scavenging activities. All the tested extracts exhibited potent cytotoxicity with sample A at LC50 values of 0.20µg/mL showed higher toxicity than control (potassium dichromate LC50 = 7.23µg/mL). Among the tested samples, sample F revealed the highest inhibitory property with IC50 value of 23.10µg/mL. Samples A and D exhibited significant inhibitory activity with IC50 values of 116.50µg/mL and 355.30µg/mL respectively. Isolated compounds from methanol extracts (sample E and F) showed better performances as antioxidant-agent against pathogens associated to attack by free radical mechanism. With current trend of drug resistance by many microorganisms, new compounds have been isolated from the root of F. capensis that showed better performance against cultured: Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Klebsiella pneumonia at different concentrations.

Synthesis and Characterization of Schiff Bases and Their Ag(I) Complexes Containing 2,5,6-Trisubstituted Imidazothiadiazole Derivatives: Molecular Docking and In Vitro Cytotoxic Effects Against Nonsmall Lung Cancer Cell Line.

In this study, four novels 2,5,6-trisubstituted imidazothiadiazole derivative ligands and their Ag(I) complexes were synthesized and characterized using various spectroscopic analysis techniques. First, imidazo[2,1-b][1,3,4]thiadiazole derivative (3) was obtained from the reaction of 5-amino-1,3,4-thiadiazole-2-thiol with benzyl bromide in the presence of KOH in an ethanolic medium. In the next step, the resultant compound reacted sequentially with four substituted phenacyl bromide derivatives (4a-4d) under refluxed ethanol for 24 h to obtain substituted 2-(benzylthio)-6-phenylimidazo[2,1-b][1,3,4]thiadiazole derivatives (5-8). Compounds (9-12) were obtained by attaching a carbonyl group to carbon number 5 of the imidazothiadiazole group in these compounds with the help of Vilsmeier-Haack reagent. The resultant compounds were reacted in an ethanolic medium to synthesize the novel (13-16) ligands by adding ethylenediamine in a 1:2 molar ratio. The Ag(I) complexes of the resultant ligands were synthesized by mixing silver acetate with the ligands in a dimethyl sulfoxide medium to obtain (17-20) complexes. All the synthesized compounds were analyzed using FTIR, 1H NMR, 13C NMR, mass spectroscopy, magnetic susceptibility, ICP-OES, and thermogravimetric analysis techniques. The study also investigates the in vitro cytotoxic effect of the ligands and complexes on A549 (nonsmall cell lung cancer) cells using the MTT assay and shows that the 13, 15, and 16 ligands, together with their complexes, exhibit potent cytotoxicity. In addition, in silico molecular docking simulations were conducted both to support the in vitro cytotoxicity experiments and to ascertain the active binding sites and interactions of the ligands and complexes on the EGFR receptor. The result indicates that ligands and complexes may serve as promising candidates for further investigation as anticancer agents.

Chemical Transformation of Vaping Emissions under Indoor Atmospheric Aging Processes.

E-cigarette emissions, which contain a variety of hazardous compounds, contribute significantly to indoor air pollution and raise concerns about secondhand exposure to vaping byproducts. Compared to fresh vape emissions, our understanding of chemically aged products in indoor environments remains incomplete. Terpenes are commonly used as flavoring agents in e-liquids, which have the ability to react with the dominant indoor oxidant ozone (O3) to produce reactive oxygenated byproducts and result in new particle formation. In this study, mixtures of propylene glycol (PG), vegetable glycerin (VG), and terpenes as e-liquids were injected into a 2 m3 FEP chamber to simulate the indoor aging process. 100 ppbv O3 was introduced into the chamber and allowed to react with the fresh vape emissions for 1 h. Complementary online and offline analytical techniques were used to characterize the changes in the aerosol size distribution and chemical composition during the aging processes. We observed more ultrafine particles and a greater abundance of highly oxygenated species, such as carbonyls, in aged e-cigarette aerosols. Compared with their fresh counterparts, the aged emissions exhibited greater cytotoxic potential, which can be attributed to the formation of these highly oxygenated compounds that are not present in the fresh emissions. This work highlights the dynamic chemistry and toxicity of e-cigarette aerosols in the indoor environment as well as the indirect risks of secondhand exposure.

Unveiling the multifaceted bioactivity of copper(II)-Schiff base complexes: a comprehensive study of antioxidant, anti-bacterial, anti-inflammatory, enzyme inhibition and cytotoxic potentials with DFT insights.

The rise of various diseases demands the development of new agents with antioxidant, antimicrobial, anti-inflammatory, enzyme-inhibiting, and cytotoxic properties. In this study, heterocyclic Schiff base complexes of Cu(II) featuring a benzo[b]thiophene moiety were synthesized and their biological activities evaluated. The complexes were characterized using FT-IR, UV-Vis, and EPR spectroscopy, TG-DTG analysis, magnetic moment measurements, molar conductivity measurements, and elemental analyses. Density functional theory (DFT) calculations were used to optimize the theoretical molecular orbital energies of the copper complexes. The complexes exhibited square pyramidal and square planar geometries. Biological assays demonstrated that these complexes generally outperformed the Schiff base ligands for various activities. The antioxidant capacity, measured via the DPPH assay in methanol, was comparable to those of the BHT and ascorbic acid standards, with 4BNPC showing the lowest IC50 value, which was attributed to the free OH group rather than coordination to the metal center. The anti-bacterial activity was assessed using the agar disc diffusion method against E. coli, P. aeruginosa, B. subtilis, and S. aureus, with BAC showing the largest inhibition zone compared to the others and ciprofloxacin as the reference. The anti-inflammatory activity, evaluated by the HRBC membrane stabilization method, showed that the 4BNPC Cu(II) complex had moderate activity similar to that of diclofenac. Enzyme inhibition studies against α-amylase revealed that the BAC complexes had the highest inhibition values, surpassing those of the Schiff base ligands. Cytotoxicity was assessed using Trypan blue exclusion for DLA and HepG2 cancer cell lines, and the MTT assay for H9c2 human cells. BMPC demonstrated superior cytotoxicity at both high and low concentrations against the normal H9c2 cell line. Among the tested compounds, BNPC showed moderate inhibition against HepG2 cells, while BMPC exhibited the greatest cytotoxicity at higher concentrations, particularly reaching nearly 100% cell death at 200 μg mL-1 in DLA cell lines. This suggests that BMPC is a promising candidate for further pharmacological research, particularly against DLA cells.