Cytotoxic Activity Research Articles

Alliaceumolide A: A rare undescribed 17-membered macrolide from Indonesian Dysoxylum alliaceum

Alliaceumolide A (1), a new macrolide together with known ivorenolide B (2) were isolated from Dysoxylum alliaceum (Blume) Blume ex A.Juss. These compounds were classified as 17-membered macrolide, which is a rare structure for plant-derived natural products. The structures were elucidated by extensive spectroscopic analyses, and the absolute configuration of 1 was determined by electronic circular dichroism (ECD) using TDDFT method. Furthermore, compounds 1 and 2 were tested for cytotoxic activity against two cancer MCF-7 and HeLa cell lines.

Generation of xanthohumol derivatives through fungi-mediated biotransformation

Xanthohumol (XTH, 1), a major prenylated chalcone in hops, has attracted considerable interests because of its pharmaceutical potency. To explore more related derivatives of XTH, its biotransformation was performed using the in vitro microbial model. Fungus Mucor sp. exhibited a robust biocatalytic feature to transform the substrate. Preparative fungi-mediated biotransformation led to the isolation of two new (2 and 5) and eight known (3, 4 and 6-11) metabolites. The two new metabolites were identified as (2″R)-dihydroxanthohumol B (2) and xanthohumol L 4′-O-β-D-glucopyranoside (5) based on the combined spectroscopic analysis. According to the cytotoxic activities of all metabolites, compounds 7 and 9 showed relatively sensitive cytotoxic activity against A375 and A549 cancer cell lines, respectively. These findings not only provided a biological approach to achieve the derivatives of XTH but also gave an information for the lead optimisation of XTH for the development of potential anti-cancer agents.

Design, synthesis and evaluation of new methyl piperazine derivatives as anticancer agents

BackgroundTo overcome the problem of side effects and toxicity, development of new anticancer agents is needed. Recently, piperidine salicylanilide derivatives with nanomolar epidermal growth factor receptor (EGFR) inhibitory and cytotoxicity activity have been reported. In the present study effect of replacing piperidine in reported piperidine salicylanilide with N-methyl piperazine and changing substituent’s of phenyl ring at other end on anticancer activity have been explored. A series of sixteen methyl piperazine incorporated phenyl benzamide and phenyl methanone derivatives have been synthesized and tested in a panel of three cancer cell lines (adenocarcinomic human alveolar basal epithelial cells (A-549), human colon carcinoma (HCT-116) and human pancreatic carcinoma (MIAPaCa-2)), using gefitinib as standard. Further, to study the probable mechanism, due to their structural similarity with EGFR inhibitors, docking interactions with EGFR active site were observed using Schrodinger suite.ResultThe results indicated that most of the compounds showed promising activity; out of which, compound A-11 was most active having cytotoxicity much better than that of gefitinib. It showed IC50 value of 5.71 µM against A-549 cell line, 4.26 µM against HCT-116 colon cancer line and 31.36 µM against MIAPaCa-2 cell line.ConclusionIt was found that these compounds fit well in the active site and may be exhibiting anticancer activity via EGFR inhibition.Graphical

Synthesis, characterization and bioactivity of new pyridine-2(H)-one, nicotinonitrile, and furo[2,3-b]pyridine derivatives.

Pyridone heterocycles, such as furo[2,3-b]pyridines, have emerged as prominent scaffolds in medicinal chemistry due to their versatile pharmacological properties, including significant anticancer activity. In this study, we successfully synthesized new pyridine-2(H)-one, nicotinonitrile, and furo[2,3-b]pyridine derivatives from chalcones bearing 4-(benzyloxy)phenyl and dichlorothiophenyl subunits to explore their therapeutic potential against breast cancer. By employing a synthetic strategy involving Claisen-Schmidt condensation followed by sequential cyclizations and functional modifications, we synthesized and characterized four compounds (MI-S0, MI-S1, MI-S2, and MI-S3) using various spectroscopic methods, including FT-IR, 1H-NMR, 13C-NMR, DEPT, H,H- and C,H-COSY, and HRMS. The in vitro cytotoxic activity of these compounds was evaluated against two breast cancer cell lines, MCF-7 and MDA-MB-231, and compared with a noncancerous breast cell line, MCF-10A. All compounds exhibited potent cytotoxic activities with minimal selectivity toward normal cells. Molecular docking studies targeting the serine/threonine kinase AKT1, estrogen receptor alpha (ERα), and human epidermal growth factor receptor 2 (HER2) revealed strong binding affinities, suggesting a mechanism involving the disruption of key cellular signaling pathways. These findings underscore the potential of furo[2,3-b]pyridine derivatives as promising candidates for further development into anticancer agents, laying the groundwork for future investigations into their selective therapeutic efficacy and molecular mechanisms of action.

Synthesis, structural interpretation, DFT, molecular docking, antimicrobial assessment and cytotoxic profiling of a cadmium(II) hydroxamate complex: in vitro and in silico investigations

A Cd(II) complex of composition Cd(C11H9CONHO)2 has been synthesized by treating CdCl2 (anhydrous) with potassium 1-naphthaleneacetohydroxamate (C11H9CONHOK) (KHL) in 1:2 molar ratio in MeOH. Various physicochemical studies including elemental analysis, molar conductivity, FTIR, UV-visible,1H and 13C NMR spectroscopic techniques were employed to interpret the structure of the complex. O,O-Coordination has been proposed through the carbonyl and hydroxamic oxygen atoms and a distorted tetrahedral geometry around cadmium is supported by physicochemical and computational studies. Density Functional Theory studies have shown the stability of the complex and predict various structural parameters (bond lengths and angles). Chemical reactivity descriptors and Mulliken charge analysis were also calculated and analyzed. Molecular docking studies were conducted to analyze the interaction of the ligand and complex with two proteins, Escherichia coli Tem1 beta-lactamase (PDB ID = 1BTL) and Alternaria alternata major allergen alt a 1 (PDB ID = 4AUD). Further, the ligand and complex were tested in vitro for their antimicrobial activity against selected microbes such as S. aureus, S. typhi, E. coli, S. flexneri, Rhizoctonia solani, Alternaria alternata, and Fusarium Sambucinum. The complex was more effective against A. alternata, showing inhibition specifically against S. typhi and E. coli. In vitro cytotoxicity studies were conducted on Rhabdomyosarcoma RD cancer cell lines. The results revealed a reduction in cell viability, correlating with increasing concentrations of the compounds, thereby indicating efficient cytotoxic activity.

Cardiac glycosides with cytotoxic activity from the seeds of Thevetia peruviana

Phytochemical investigation on the extract of the seeds of Thevetia peruviana resulted in the isolation of six new cardiac glycosides, namely theveperosides A-F (1–6), including a rare 19-nor-cardenolide (1), together with seven known analogues (7–13). The chemical structures of these compounds were determined based on detailed spectroscopic analysis. The cytotoxic activities of 1–13 were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cell lines, and their structure-activity relationships (SARs) were investigated. Compound 3 exhibited the significant cytotoxic effects with IC50 values ranging from 0.032 to 0.055 μΜ, which could induce HepG2 cells apoptosis in a dose-dependent manner.

Assessment of Antimicrobial and Cytotoxic Activities of Liposomes Loaded with Curcumin and Lippia origanoides Essential Oil.

(1) Introduction: Curcumin and Lippia origanoides essential oils have a broad spectrum of biological activities; however, their physicochemical instability, low solubility, and high volatility limit their therapeutic use. Encapsulation in liposomes has been reported as a feasible approach to increase the physicochemical stability of active substances, protect them from interactions with the environment, modulate their release, reduce their volatility, improve their bioactivity, and reduce their toxicity. To date, there are no reports on the co-encapsulation of curcumin and Lippia origanoides essential oils in liposomes. Therefore, the objective of this work is to prepare and physiochemical characterize liposomes loaded with the mixture of these compounds and to evaluate different in vitro biological activities. (2) Methods: Liposomes were produced using the thin-layer method and physiochemical characteristics were calculated. The antimicrobial and cytotoxic activities of both encapsulated and non-encapsulated compounds were evaluated. (3) Results: Empty and loaded nanometric-sized liposomes were obtained that are monodisperse and have a negative zeta potential. They inhibited the growth of Staphylococcus aureus and did not exhibit cytotoxic activity against mammalian cells. (4) Conclusions: Encapsulation in liposomes was demonstrated to be a promising strategy for natural compounds possessing antimicrobial activity.

Phytochemistry and Bioactivities of Duguetia furfuracea (A.St.-Hil.) Saff.

Duguetia furfuracea, belonging to the Annonaceae family, is a perennial plant found in the Central-West, Southeast, and Northeast regions of Brazil, known for its various uses in traditional medicine. Used as a hypocholesterolemic, anorexigenic, and for treating various conditions including cancer and infections, its medicinal properties have garnered scientific interest. Studies have identified several bioactive compounds in different parts of the plant. The leaves contain phenolic acids, flavonoids, and alkaloids such as duguetine and dicentrinone, which exhibit antioxidant, anti-inflammatory, and antimicrobial properties. Phytochemical analysis revealed the presence of rare sesquiterpenes such as α-santalene and (-)-ishwarane, strengthening the chemotaxonomic relationship between Annonaceae and Aristolochiaceae. The species has shown larvicidal activity against Aedes aegypti, pediculicidal activity against Pediculus capitis, and antiplasmodial activity against Trypanosoma cruzi. Additionally, it possesses anti-inflammatory, antinociceptive, and cytotoxic activities, being effective against Candida spp. strains and cancer cells. However, its toxicity was observed in studies with Drosophila melanogaster and cellular models, indicating the need for further studies to ensure its safe use. The plant shows potential for therapeutic applications due to its chemical diversity, but it is essential to deepen investigations into its mechanisms of action and develop extraction and isolation methods to maximize its medicinal potential safely and effectively. Continued research is crucial to integrate D. furfuracea into modern phytotherapy and the development of new drugs. The presence of these bioactive compounds highlights the importance of exploring the full pharmacological potential of D. furfuracea for future therapeutic advancements, emphasizing its promising role in natural medicine. the pharmacological properties of D. furfuracea underscore its potential for innovative drug development and traditional medicinal enhancement.

GC-MS analysis and pharmacological potentiality of Lasia spinosa (L.) Thwaites leaves and fruit extracts: an in vitro and in silico studies.

Lasia spinosa (L. spinosa) is widely used in Asian countries for treating various diseases and as a vegetable, yet its bioactive properties remain under-researched. It is traditionally utilized in Ayurveda and the AYUSH system of medicine for its medicinal properties, and commonly used to treat digestive disorders, respiratory issues, and inflammatory conditions. This study aims to identify the phytochemicals in L. spinosa leaves and fruit extracts and evaluate their biological activities. Phytochemicals in methanol extracts of L. spinosa fruits and leaves were identified by GC-MS analysis. Antioxidant and cytotoxic activities were assessed using the DPPH free radical and nitric oxide (NO) scavenging assay and brine shrimp lethality test. Antibacterial activity was evaluated against Shigella boydii, Shigella flexneri, Streptococcus iniae, and Streptococcus dysgalactiae, while antifungal properties were tested against Cercospora beticola and Rhizoctonia solani. Molecular docking was conducted to predict the effectiveness of L. spinosa phytochemicals against NADPH oxidase and the Shigella effector OspG. Nine compounds were detected from both extracts. The methanol leaves extract exhibited superior antioxidant activity compared to the fruit extract, with IC50 values of 111.81 ± 8.99µg/ml and 174.81 ± 4.86µg/ml, respectively, as determined by the DPPH scavenging assay. The nitric oxide (NO) scavenging assay also revealed higher potency in the leaves extract (IC50 = 138.59 ± 1.50µg/ml) compared to the fruit extract (IC50 = 196.47 ± 1.72µg/ml). Both extracts showed significant antimicrobial activity against all tested microorganisms. In silico studies indicated notable inhibitory activity of all phytochemicals against the target proteins, with Linoelaidic acid and 9-Octadecenamide, (Z)- exhibiting the highest activity against NADPH oxidase (PDB: 2cdu) and Shigella flexneri OspG effector kinase (PDB: 4bvu), respectively. These findings suggest that L. spinosa has potent antioxidant and antimicrobial activities. Compounds from this plant could serve as lead compounds for developing antioxidant and antibacterial agents. However, molecular studies should be addressed.

A dual-targeting approach with anti-IL10R CAR-T cells engineered to release anti-CD33 bispecific antibody in enhancing killing effect on acute myeloid leukemia cells.

Immunotherapies, including chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs), encounter several challenges in the management of acute myeloid leukemia (AML), including limited persistence of these treatments, antigen loss and resistance of leukemia stem cells (LSCs) to therapy. Here, we proposed a novel dual-targeting approach utilizing engineered anti-IL10R CAR-T cells to secrete bispecific antibodies targeting CD33. This innovative strategy, rooted in our previous research which established a connection between IL-10 and the stemness of AML cells, designed to improve targeting efficiency and eradicate both LSCs and AML blasts. We first demonstrated the superior efficacy of this synergistic approach in eliminating AML cell lines and primary cells expressing different levels of the target antigens, even in cases of low CD33 or IL10R expression. Furthermore, the IL10R CAR-T cells that secret anti-CD33 bsAbs (CAR.BsAb-T), exhibited an enhanced activation and induction of cytotoxicity not only in IL10R CAR-T cells but also in bystander T cells, thereby more effectively targeting CD33-positive tumor cells. Our in vivo experiments provided additional evidence that CAR.BsAb-T cells could efficiently redirect T cells, reduce tumor burden, and demonstrate no significant toxicity. Additionally, delivering bsAbs locally to the tumor sites through this strategy helps mitigate the pharmacokinetic challenges typically associated with the rapid clearance of prototypical bsAbs. Overall, the engineering of a single-vector targeting IL10R CAR, which subsequently secretes CD33-targeted bsAb, addresses the issue of immune escape due to the heterogeneous expression of IL10R and CD33, and represents a promising progress in AML therapy aimed at improving treatment outcomes.

Unraveling the Bioactive Potential of Camellia japonica Edible Flowers: Profiling Antioxidant Substances and In Vitro Bioactivity Assessment.

In recent years, the search for novel natural-based ingredients by food and related industries has sparked extensive research aimed at discovering new sources of functional molecules. Camellia japonica, traditionally known as an ornamental plant, has gained attention due to its diverse array of bioactive compounds with potential industrial applications. Although C. japonica flowers are edible, their phytochemical profile has not been thoroughly investigated. In this study, a phenolic profile screening through an HPLC-ESI-QQQ-MS/MS approach was applied to C. japonica flower extracts, revealing a total of 36 compounds, including anthocyanins, curcuminoids, dihydrochalcones, dihydroflavonols, flavonols, flavones, hydroxybenzoic acids, hydroxycinnamic acids, isoflavonoids, stilbenes, and tyrosols. Following extract profiling, their bioactivity was assessed by means of in vitro antioxidant, antimicrobial, cytotoxic, and neuroprotective activities. The results showed a multifaceted high correlation of phenolic compounds with all the tested bioactivities according to Pearson's correlation analysis, unraveling the potential of C. japonica flowers as promising sources of nutraceuticals. Overall, these findings provide insight into the valorization of C. japonica flowers from different unexplored cultivars thus diversifying their industrial outcome.

Marizomib (Salinosporamide A) Promotes Apoptosis in A375 and G361 Melanoma Cancer Cells.

Malignant melanoma-a tumor originating from melanocytes-is characterized by dynamic growth and frequent metastases in the early stage of development. Current therapy methods are still insufficient, and there is a need to search for new ways of treating this malady. The induction of apoptosis-physiological cell death-by proteasome inhibitors is recognized as an effective method of non-invasive elimination of cancer cells. In our research, we wanted to check the potential of marizomib (MZB, salinosporamide A, NPI-0052)-an irreversible proteasome inhibitor derived from the marine actinomycete Salinispora tropica-to induce apoptosis in A375 and G361 malignant melanoma cells. We determined the cytotoxic activity of marizomib by performing an MTT test. Ethidium bromide and acridine orange staining demonstrated the disruption of membrane integrity in the examined cell lines. We confirmed the proapoptotic activity of marizomib by flow cytometry with the use of an FITC-Annexin V assay. A Western blot analysis presented an increase in the expression of proteins related to endoplasmic reticulum (ER) stress as well as markers of the apoptosis. The gathered findings suggest that marizomib induced the ER stress in the examined melanoma cancer cells and directed them towards the apoptosis pathway.

Structures of bicyclic hexapeptides RA-XXVII and RA-XXVIII from Rubia cordifolia L.

Two bicyclic hexapeptides RA-XXVII and RA-XXVIII, featuring a phenylpropanoid unit attached to the aromatic ring of the Tyr-6 residue of deoxybouvardin, were isolated from the roots of Rubia cordifolia L. Their structures were determined on the basis of spectroscopic data and X-ray crystallography of the 4-O-methyl derivative of RA-XXVII, and the semisynthesis from deoxybouvardin and coniferyl alcohol. RA-XXVII and RA-XXVIII exhibited cytotoxic activity with IC50 values of 0.051 and 0.18 μM, respectively, against the HL-60 cell line, and 0.18 and 0.78 μM, respectively, against the HCT-116 cell line.

Preclinical evaluation of CXCR4 peptides for targeted radionuclide therapy in glioblastoma

BackgroundGlioblastoma (GBM), is the most fatal form of brain cancer, with a high tendency for recurrence despite combined treatments including surgery, radiotherapy, and chemotherapy with temozolomide. The C-X-C chemokine receptor 4 (CXCR4) plays an important role in tumour radioresistance and recurrence, and is considered as an interesting GBM target. TRT holds untapped potential for GBM treatment, with CXCR4-TRT being a promising strategy for recurrent GBM treatment. Our study focuses on the preclinical assessment of different 177Lu-labelled CXCR4-targeting peptides, CTCE-9908, DV1-K-DV3, and POL3026 for GBM treatment and exploring some of the radiobiological mechanisms underlying these therapies.ResultsAll three DOTA-conjugated peptides could be radiolabelled with 177Lu with > 95% radiochemical yield. Binding studies show high specific binding of [177Lu]Lu-DOTA-POL3026 to U87-CXCR4 + cells, with 42% of the added activity binding to the membrane at 1 nM, and 6.5% internalised into the cells. In the presence of the heterologous CXCR4 blocking agent, AMD11070, membrane binding was reduced by 95%, a result confirmed by quantitative in vitro autoradiography of orthotopic GBM xenograft sections. An activity-dependent decrease in cell viability was observed for [177Lu]Lu-DOTA-DV1-K-DV3 and [177Lu]Lu-DOTA-POL3026, along with a slight increase in the induction of apoptotic markers. Additionally, the expression of γH2AX increased in a time-and activity-dependent manner. Ex vivo biodistribution studies with [177Lu]Lu-DOTA-POL3026 show uptake in the tumour reaching a SUV of 1.9 at 24 h post-injection, with higher uptake in the kidneys, lungs, spleen, and liver. Dosimetry estimations show an absorbed dose of 0.93 Gy/MBq in the tumour. A blocking study with AMD11070 showed a 38% reduction in tumour uptake, with no significant reduction observed in µSPECT imaging. Although no brain uptake was observed in the ex vivo biodistribution study, autoradiography on U87-CXCR4 + tumour inoculated mouse brain slices shows non-specific binding in the brain, next to high specific binding to the tumour.ConclusionsIn conclusion, we compared different 177Lu-radiolabelled CXCR4-targeting peptides for their binding potential in GBM, and demonstrated their varied cytotoxic action against GBM cells in vitro, with POL3026 being the most promising, causing considerable DNA damage. Though the peptide’s systemic biodistribution remains to be improved, our data demonstrate the potential of [177Lu]Lu-DOTA-POL3026 for CXCR4-TRT in the context of GBM.

Exploring the ethnopharmacological significance of Cynara scolymus bracts: Integrating metabolomics, in-Vitro cytotoxic studies and network pharmacology for liver and breast anticancer activity assessment

Ethnopharmacological relevanceLiver and breast cancers are the most dominant cancer types with high occurrence rates. Artichoke (Cynara scolymus L.) has been reputed for its traditional use in alleviating many liver and gallbladder ailments beside its anticancer activity against various types of cancer cells. Aim of the studyTo demonstrate detailed chemical matrices of the different plant parts and evaluate their cytotoxic activities aiming to unveil the relationship between these activities and the intrinsic metabolites using metabolomic studies, in-vitro experiments and network pharmacology. Materials and methodsChemical profiling of extracts from the different plant parts (stems, leaves, bracts and receptacles) was performed using HPLC/QqQ/MS followed by unsupervised chemometric studies. In-vitro cytotoxic potentials of the extracts were evaluated on breast and liver cancer cell line then an OPLS study using linear regression was conducted. Consequently, a network pharmacology analysis on the most bioactive plant organ was applied. ResultsUnsupervised chemometric analysis revealed that kaempferol-3-O-α-L-rhamnopyranoside-7-O-β-D-galacturonopyranoside, chrysoeriol-7-rutinoside and 1-caffeoylquinic acid were responsible for the segregation of the bract (CSB) segregated from the rest of the plant organs. Interestingly, CSB extract possessed the highest potential in-vitro cytotoxic activity against both liver and breast cancer cells (IC50 = 1.65 and 1.77 μg/mL). As expected, the aforementioned biomarkers were observed to be the discriminatory cytotoxic metabolites in the constructed supervised chemometric model. Network pharmacology analysis on CSB revealed 27 liver cancer-related metabolites of which, 1-caffeoylquinic acid was the most enriched one contributing to 13% of the total interactions. Furthermore, 38 target genes were involved, the most enriched of which were Aldo-keto reductase family 1 member B1 (AKR1B10) and interleukin-2 (IL-2). KEGG pathway analysis unveiled 23 significantly related pathways including metabolic pathways that possessed the lowest p-value (1.6E-5). ConclusionThe findings demonstrated that CSB is a significant source of cytotoxic metabolites against breast cancer and liver cancer cell lines, hence, drawing attention to the pharmaceutical and medicinal value of this negligible plant organ and paving the route for insightful research into its exact pharmacological cytotoxic mechanisms.

Stapling Cysteine[2,4] Disulfide Bond of α-Conotoxin LsIA and Its Potential in Target Delivery.

α-Conotoxins, as selective nAChR antagonists, can be valuable tools for targeted drug delivery and fluorescent labeling, while conotoxin-drug or conotoxin-fluorescent conjugates through the disulfide bond are rarely reported. Herein, we demonstrate the [2,4] disulfide bond of α-conotoxin as a feasible new chemical modification site. In this study, analogs of the α-conotoxin LsIA cysteine[2,4] were synthesized by stapling with five linkers, and their inhibitory activities against human α7 and rat α3β2 nAChRs were maintained. To further apply this method in targeted delivery, the alkynylbenzyl bromide linker was synthesized and conjugated with Coumarin 120 (AMC) and Camptothecin (CPT) by copper-catalyzed click chemistry, and then stapled between cysteine[2,4] of the LsIA to construct a fluorescent probe and two peptide-drug conjugates. The maximum emission wavelength of the LsIA fluorescent probe was 402.2 nm, which was essentially unchanged compared with AMC. The cytotoxic activity of the LsIA peptide-drug conjugates on human A549 was maintained in vitro. The results demonstrate that the stapling of cysteine[2,4] with alkynylbenzyl bromide is a simple and feasible strategy for the exploitation and utilization of the α-conotoxin LsIA.

Spleen Tyrosine Kinase (SYK) negatively regulates ITAM-mediated human NK cell signaling and CD19-CAR NK cell efficacy.

NK cells express activating receptors that signal through ITAM-bearing adapter proteins. The phosphorylation of each ITAM creates binding sites for SYK and ZAP70 protein tyrosine kinases to propagate downstream signaling including the induction of Ca 2+ influx. While all immature and mature human NK cells co-express SYK and ZAP70, clonally driven memory or adaptive NK cells can methylate SYK genes and signaling is mediated exclusively using ZAP70. Here, we examined the role of SYK and ZAP70 in a clonal human NK cell line KHYG1 by CRISPR-based deletion using a combination of experiments and mechanistic computational modeling. Elimination of SYK resulted in more robust Ca ++ influx after cross-linking of the CD16 and NKp30 receptors and enhanced phosphorylation of downstream proteins, whereas ZAP70 deletion diminished these responses. By contrast, ZAP70 depletion increased proliferation of the NK cells. As immature T cells express both SYK and ZAP70 but mature T cells often express only ZAP70, we transduced the human Jurkat cell line with SYK and found that expression of SYK increased proliferation but diminished TCR-induced Ca 2+ flux and activation. We performed transcriptional analysis of the matched sets of variant Jurkat and KHYG1 cells and observed profound alterations caused by SYK expression. As depletion of SYK in NK cells increased their activation, primary human NK cells were transduced with a CD19-targeting CAR and were CRISPR edited to ablate SYK or ZAP70 . Deletion of SYK resulted in more robust cytotoxic activity and cytokine production, providing a new therapeutic strategy of NK cell engineering for cancer immunotherapy.

ATP-hydrolyzing, DNA-damaging and cytotoxic activities of peptide-targeted cobalt(III) complex with diethylentriamine

ATP-hydrolyzing, DNA-damaging and cytotoxic activities of peptide-targeted cobalt(III) complex with diethylentriamine

Exploring the antitumor potential of novel quinoline derivatives via tubulin polymerization inhibition in breast cancer; design, synthesis and molecular docking.

A series of quinoline derivatives was designed and synthesized as novel tubulin inhibitors targeting the colchicine binding site. All the rationalized compounds 3a-e, 4a-e, 5a-e, and 6a-e have been chosen for screening their cytotoxic activity against 60 cell lines by NCI. Compounds 3b, 3c, 4c, 5c and 6c demonstrated the most notable antitumor activity against almost all cell lines. Compound 4c emerged as the most potent compound as an antiproliferative agent. This compound was subsequently chosen for five-dose testing and it exhibited remarkable broad-spectrum efficacy with strong antitumor activity against several cell lines. Compound 4c significantly induced cell cycle arrest in MDA-MB-231 cells at G2 and M phases where the cell population increased dramatically to 22.84% compared to the untreated cells at 10.42%. It also increased the population in MDA-MB-231 cells at both early and late stages of apoptosis. Compound 4c can successfully inhibit tubulin polymerization with an IC50 value of 17 ± 0.3 μM. The β-tubulin mRNA levels were notably reduced in MDA-MB-231 cells treated with compound 4c which is similar to the effect observed with colchicine treatment. Docking studies revealed that compound 4c interacted well with crucial amino acids in the active site.

LVI and DI-SPME Combined with GC/MS and GC/MS for Volatile Chemical Profile Investigation and Cytotoxic Power Evaluation of Essential Oil and Hydrolate from Cannabis sativa L. cv. Carmagnola.

Cannabis sativa L. is a plant that has been cultivated since ancient times thanks to its various uses. Even its extraction products, such as essential oil and hydrolate, having a varied chemical composition and rich in bioactive components, find wide use in different sectors, gathering ever-increasing interest over time. In this work, the essential oil of Cannabis sativa L. cv. Carmagnola was characterized by using Gas Chromatography/Mass Spectrometry (GC/MS) and, for the first time, the chemical profile of the hydrolate was also described through different analytical techniques such as Large-Volume Injection Gas Chromatography/Mass Spectrometry (LVI-GC/MS) and Direct Immersion-Solid Phase Microextraction-Gas Chromatography/Mass spectrometry (DI-SPME-GC/MS), in order to provide a more complete compositional profile. The results of the analyses conducted on the hydrolate highlighted a high content of α-terpineol; on the other side, in the essential oil, a prevalence of monoterpenes, with α-pinene and limonene as the characterizing components, was detected. Both matrices were also investigated to evaluate their cytotoxic activity by using a panel of cancer cell lines derived from different histotypes such as melanoma (A375, LOX IMVI), non-small cell lung cancer (H1299, A549), colon (HT29) and pancreatic (L3.6) cancer cell lines. The obtained data demonstrated that essential oil was more effective than hydrolate in terms of reduction in cell viability.