Cytotoxic and apoptotic effects of Hypericum androsaemum on prostate adenocarcinoma (PC-3) and hepatocellular carcinoma (Hep G2) cell lines with identification of secondary metabolites by LC-HRMS

The study aims to determine the secondary metabolites of Hypericum androsaemum L. extracts by liquid chromatography-high resolution mass spectrometry (LC-HRMS), and investigate the antioxidant and cytotoxic activities of the plant. Cytotoxic activity was evaluated by MTT assay, and apoptosis induction abilities on human prostate adenocarcinoma (PC-3), and hepatocellular carcinoma (Hep G2) cell lines. Accordingly, major secondary metabolites were found as hederagenin (762 ± 70.10 μg/g) in the leaves dichloromethane (LD), herniarin (167 ± 1.50 μg/g) in fruit dichloromethane (FD), (-)-epicatechin (6538 ± 235.36 μg/g) in the leaves methanol (LM), (-)-epigallocatechin gallate (758 ± 20.46 μg/g) in the fruit methanol (FM), and caffeic acid (370 ± 8.88 μg/g) in the fruit water (FW), and (3313 ± 79.51 μg/g) in the leaves water (LW) extracts. LM exerted strong antioxidant activity in DPPH free (IC₅₀ 10.94 ± 0.08 μg/mL), and ABTS cation radicals scavenging (IC₅₀ 9.09 ± 0.05 μg/mL) activities. FM exhibited cytotoxic activity with IC₅₀ values of 73.23 ± 3.06 µg/mL and 31.64 ± 2.75 µg/mL on PC-3 and Hep G2 cell lines, respectively. Being the richest extract in terms of quillaic acid (630 ± 18.9 μg/g), which is a well-known cytotoxic triterpenoid with proven apoptosis induction ability on different cells, FM extract showed apoptosis induction activity with 64.75% on PC-3 cells at 50 μg/mL concentration. The study provides promising results about the potential of Hypericum androsaemum on cancer prevention.     

Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design,Synthesis, Docking,and Biological Evaluation

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

Cytotoxic Activity and Docking Studies of 2-arenoxybenzaldehyde N-acyl Hydrazone and 1,3,4-Oxadiazole Derivatives against Various Cancer Cell Lines

To understand whether previously synthesized novel hydrazone and oxadiazole derivatives have promising anticancer effects, docking studies and in vitro toxicity assays were performed on A-549, MDA-MB-231, and PC-3 cell lines. The antiproliferative properties of the compounds were investigated using molecular docking experiments. Each compound’s best-docked poses, binding affinity, and receptor-ligand interaction were evaluated. Compounds’ molecular weights, logPs, TPSAs, abilities to pass the blood-brain barrier, GI absorption qualities, and CYPP450 inhibition have been given. When the activities of these molecules were examined in vitro, for the A-549 cell line, hydrazone 1e had the minimum IC₅₀ value of 13.39 μM. For the MDA-MB-231 cell line, oxadiazole 2l demonstrated the lowest IC₅₀ value, with 22.73 μM. For PC-3, hydrazone 1d showed the lowest C50 value of 9.38 μM. The three most promising compounds were determined as compounds 1e, 1d, and 2a based on their minimum IC₅₀ values, and an additional scratch assay was performed for A-549 and MDA-MB-231 cells, which have high migration capacity, for the three most potent molecules; it was determined that these molecules did not show a significant antimetastatic effect.     

New Organoselenium (NSAIDs-Selenourea and Isoselenocyanate) Derivatives as Potential Antiproliferative Agents: Synthesis,Biological Evaluation and in Silico Calculations

In this study, we report on the synthesis of new organoselenium derivatives, including nonsteroidal anti-inflammatory drugs (NSAIDs) scaffolds and Se functionalities (isoselenocyanate and selenourea), which were evaluated against four types of cancer cell line: SW480 (human colon adenocarcinoma cells), HeLa (human cervical cancer cells), A549 (human lung carcinoma cells), MCF-7 (human breast adenocarcinoma cells). Among these compounds, most of the investigated compounds reduced the viability of different cancer cell lines. The most promising compound 6b showed IC₅₀ values under 10 μM against the four cancer cell lines, particularly to HeLa and MCF-7, with IC₅₀ values of 2.3 and 2.5 μM, respectively. Furthermore, two compounds, 6b and 6f, were selected to investigate their ability to induce apoptosis in MCF-7 cells via modulation of the expression of anti-apoptotic Bcl-2 protein, pro-inflammatory cytokines (IL-2) and proapoptotic caspase-3 protein. The redox properties of the NSAIDs-Se derivatives were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), bleomycin-dependent DNA damage and glutathione peroxidase (GPx)-like assays. Finally, a molecular docking study revealed that an interaction with the active site of thioredoxin reductase 1 (TrxR1) predicted the antiproliferative activity of the synthesized candidates. Overall, these results could serve as a promising launch point for further designs of NSAIDs-Se derivatives as potential antiproliferative agents.     

Phytochemical and In Silico ADME/Tox Analysis of Eruca sativa Extract with Antioxidant,Antibacterial and Anticancer Potential against Caco-2 and HCT-116 Colorectal Carcinoma Cell Lines

Eruca sativa Mill. (E. sativa) leaves recently grabbed the attention of scientific communities around the world due to its potent bioactivity. Therefore, the present study investigates the metabolite profiling of the ethanolic crude extract of E. sativa leaves using high resolution-liquid chromatography-mass spectrometry (HR-LC/MS), including antibacterial, antioxidant and anticancer potential against human colorectal carcinoma cell lines. In addition, computer-aided analysis was performed for determining the pharmacokinetic properties and toxicity prediction of the identified compounds. Our results show that E. sativa contains several bioactive compounds, such as vitamins, fatty acids, alkaloids, flavonoids, terpenoids and phenols. Furthermore, the antibacterial assay of E. sativa extract showed inhibitory effects of the tested pathogenic bacterial strains. Moreover, the antioxidant activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H₂O₂) were found to be IC₅₀ = 66.16 μg/mL and 76.05 μg/mL, respectively. E. sativa also showed promising anticancer activity against both the colorectal cancer cells HCT-116 (IC₅₀ = 64.91 μg/mL) and Caco-2 (IC₅₀ = 83.98 μg/mL) in a dose/time dependent manner. The phytoconstituents identified showed promising pharmacokinetics properties, representing a valuable source for drug or nutraceutical development. These investigations will lead to the further exploration as well as development of E. sativa-based nutraceutical products.     

Synthesis and Biological Activity Evaluation of Coumarin-3-Carboxamide Derivatives

A series of novel coumarin-3-carboxamide derivatives were designed and synthesized to evaluate their biological activities. The compounds showed little to no activity against gram-positive and gram-negative bacteria but specifically showed potential to inhibit the growth of cancer cells. In particular, among the tested compounds, 4-fluoro and 2,5-difluoro benzamide derivatives (14b and 14e, respectively) were found to be the most potent derivatives against HepG2 cancer cell lines (IC₅₀ = 2.62–4.85 μM) and HeLa cancer cell lines (IC₅₀ = 0.39–0.75 μM). The activities of these two compounds were comparable to that of the positive control doxorubicin; especially, 4-flurobenzamide derivative (14b) exhibited low cytotoxic activity against LLC-MK2 normal cell lines, with IC₅₀ more than 100 μM. The molecular docking study of the synthesized compounds revealed the binding to the active site of the CK2 enzyme, indicating that the presence of the benzamide functionality is an important feature for anticancer activity.     

Synthesis and Cytotoxic Activity of 1,2,4-Triazolo-Linked Bis-Indolyl Conjugates as Dual Inhibitors of Tankyrase and PI3K

A series of new 1,2,4-triazolo-linked bis-indolyl conjugates (15a–r) were prepared by multistep synthesis and evaluated for their cytotoxic activity against various human cancer cell lines. It was observed that they were more susceptible to colon and breast cancer cells. Conjugates 15o (IC₅₀ = 2.04 μM) and 15r (IC₅₀ = 0.85 μM) illustrated promising cytotoxicity compared to 5-fluorouracil (5-FU, IC₅₀ = 5.31 μM) against the HT-29 cell line. Interestingly, 15o and 15r induced cell cycle arrest at the G₀/G₁ phase and disrupted the mitochondrial membrane potential. Moreover, these conjugates led to apoptosis in HT-29 at 2 μM and 1 μM, respectively, and also enhanced the total ROS production as well as the mitochondrial-generated ROS. Immunofluorescence and Western blot assays revealed that these conjugates reduced the expression levels of the PI3K-P85, β-catenin, TAB-182, β-actin, AXIN-2, and NF-κB markers that are involved in the β-catenin pathway of colorectal cancer. The results of the in silico docking studies of 15r and 15o further support their dual inhibitory behaviour against PI3K and tankyrase. Interestingly, the conjugates have adequate ADME-toxicity parameters based on the calculated results of the molecular dynamic simulations, as we found that these inhibitors (15r) influenced the conformational flexibility of the 4OA7 and 3L54 proteins.     

Bioassay-Guided Identification of the Antiproliferative Compounds of Cissus trifoliata and the Transcriptomic Effect of Resveratrol in Prostate Cancer Pc3 Cells

The bioassay-guided fractionation of a CHCl₃-MeOH extract from the stems of Cissus trifoliata identified an active fraction against PC3 prostate cancer cells. The treatment for 24 h showed an 80% reduction in cell viability (p ≤ 0.05) by a WST-1 assay at a concentration of 100 μg/mL. The HPLC-QTOF-MS analysis of the fraction showed the presence of coumaric and isoferulic acids, apigenin, kaempferol, chrysoeriol, naringenin, ursolic and betulinic acids, hexadecadienoic and octadecadienoic fatty acids, and the stilbene resveratrol. The exposure of PC3 cells to resveratrol (IC₂₅ = 23 μg/mL) for 24 h induced significant changes in 847 genes (Z-score ≥ ±2). The functional classification tool of the DAVID v6.8 platform indicates that the underlying molecular mechanisms against the proliferation of PC3 cells were associated (p ≤ 0.05) with the process of differentiation and metabolism. These findings provide experimental evidence suggesting the potential of C. trifoliata as a promising natural source of anticancer compounds.     

Abeliaside,a new phenolic glucoside from Abelia triflora

A new phenolic glucoside, abeliaside, along with four known compounds, 5,6,7,4′-tetrahydroxy flavones, caffeic acid, 4-O-caffeoylquinic acid and caffeic acid glucoside, was isolated from the leaves of Abelia triflora R. Br. (Caprifoliaceae). The structure of the new compound was elucidated by different spectroscopic techniques. Compounds 1–5 were assayed for their anticancer activities against two cancerous human cell lines, MCF-7 and PC-3 cells, and normal Vero cell line using the crystal violet staining method. From the results it could be seen that caffeic acid possessed the highest anticancer effect against MCF-7 (IC₅₀: 17 μg/mL) and PC-3 (IC₅₀: 20.1 μg/mL) compared to vinblastine sulphate as reference drug (IC₅₀: 4.6, 2.8 μg/mL). The other compounds showed weak anticancer activity on both cell lines.     

Synthesis and antitumor activity of some new pyrazolo[1,5-a] pyrimidines

New series of pyrazolo[1,5-a]pyrimidine derivatives 7a-i, 11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines, namely colorectal carcinoma (HCT116), prostate adenocarcinoma (PC-3) and liver carcinoma (HepG-2) using MTT cytotoxicity assay at 100 μg/mL. Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells. Whereas, compounds 7d and 11a showed better antitumor activity than the rest of the compounds against both cell lines. A structure-activity relationship (SAR) has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data (MS, IR, ¹H NMR and ¹³C NMR) and elemental analysis.     

Synthesis and cytotoxic activity of new indolylpyrrole derivatives

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

Twelve New Seco-Pregnane Glycosides from Cynanchum taihangense

For our interest in the potential biologically active and structurally unique steroidal glycosides, continued phytochemical investigation of Cynanchum taihangense was carried out; twelve new seco-pregnane glycosides, cynataihosides I–L (1–4), M-T (7–14), and two known glycosides, glaucoside A (5) and atratcynoside F (6), were isolated from the 95% ethanol extract of Cynanchum taihangense. Two new aglycones were found among compounds 10, 11, 13, and 14. The structures of the glycosides were elucidated based on 1D and 2D NMR spectroscopic data, HR-ESI-MS analysis, and chemical evidence. The cytotoxicity of compounds against three human tumor cell lines (HL-60, THP-1, and PC-3) were evaluated by MTT assay. Compound 11 displayed significant cytotoxicity against THP-1 and PC-3 cell line with IC₅₀ values of 5.08 and 22.75 μm, respectively. Compounds 3 and 14 exhibited moderate and selective cytotoxicity on HL-60 and THP-1 with IC₅₀ values of 17.78 and 16.02 μm, respectively.     

Discovery of Novel Quinazoline Derivatives as Potent Antitumor Agents

In this work, we designed and synthesized a novel series of quinazoline derivatives 6–19 and then evaluated their broad-spectrum antitumor activity against MGC-803, MCF-7, PC-9, A549, and H1975, respectively. Most of them demonstrated low micromolar cytotoxicity towards five tested cell lines. In particular, compound 18 exhibited nanomolar level inhibitory activity against MGC-803 cells with an IC₅₀ value of 0.85 μM, indicating approximately a 32-fold selectivity against GES-1 (IC₅₀ = 26.75 μM). Further preclinical evaluation showed that compound 18 remarkably inhibited the migration of MGC-803 cells, induced cell cycle arrest at G2/M, and induced MGC-803 apoptosis, resulting in decreasing the expression of both Bcl-2 and Mcl-1, and up-regulating the expression of both Bax and cleaved PARP. No death or obvious pathological damage was observed in mice by acute toxicity assay. The in vivo antitumor evaluation suggested that compound 18 significantly decreased the average tumor volume and tumor weight without any effect on body weight, which is better than 5-Fu. Therefore, compound 18 can be used as a lead compound for the further development of antitumor drugs in the future.     

Diversified Chaetoglobosins from the Marine-Derived Fungus Emericellopsis sp. SCSIO41202

Two undescribed cytochalasins, emeriglobosins A (1) and B (2), together with nine previously reported analogues (3–11) and two known tetramic acid derivatives (12, 13) were isolated from the solid culture of Emericellopsis sp. SCSIO41202. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis and the calculated ECD. Some of the isolated compounds were evaluated for their cytotoxicity and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro. Among them, 8 showed potent AChE inhibitory activity, with an IC₅₀ value of 1.31 μM, and 5 showed significant cytotoxicity against PC-3 cells, with an IC₅₀ value of 2.32 μM.     

Optimization of Extraction Conditions and Cytotoxic Activity of Rapanone in Comparison to Its Homologue,Embelin

Rapanone is a plant-derived simple alkyl-dihydroxybenzoquinone structurally close to embelin, a well-known cytotoxic agent. The pharmacological characterization of rapanone is still incomplete, and to fill the data gap, a good source for its acquisition is required to conduct further research. This study aimed to optimize the conditions for the extraction of rapanone from the leaves of white-berried Ardisia crenata Sims. For this purpose, three methods were employed: heat reflux (HRE), shaking (SE), and ultrasound-assisted extraction (UAE), and such parameters as the extraction time, solvent, and the number of extractions from the same sample were set as experimental variables. Furthermore, cytotoxic activity toward prostate cancer, thyroid cancer, and colorectal carcinoma cell lines was investigated and compared with doxorubicin and embelin. The most effective and economical method for the extraction of rapanone was shown to be 20 min UAE with ethyl acetate or chloroform. Rapanone exhibited high cytotoxic activity against PC3 (IC₅₀ = 6.50 μg/mL), Du145 (IC₅₀ = 7.68 μg/mL), FTC133 (IC₅₀ = 6.01 μg/mL), 8505C (IC₅₀ = 7.84 μg/mL), and Caco-2 (IC₅₀ = 8.79 μg/mL) cell lines after 24 h and against the HT29 cell line after 48 h (IC₅₀ = 11.67 μg/mL). Furthermore, it revealed a more favorable safety profile than either its homologue, embelin, or doxorubicin. The set of optimal extraction parameters obtained may be utilized for scientific and industrial purposes to achieve the best rapanone yield. Moreover, this benzoquinone revealed a high cytotoxic activity with good selectivity.     

Lanostane Triterpenoids and Ergostane Steroids from Ganoderma luteomarginatum and Their Cytotoxicity

Macrofungus Ganoderma luteomarginatum is one of the main species of Ganoderma fungi distributed in Hainan province of China, the fruiting bodies of which have been widely used in folk as a healthy food to prevent tumors. To explore the potential cytotoxic constituents from G. luteomarginatum, the phytochemical investigation on the ethyl acetate soluble fraction of 95% ethanolic extract from the fruiting bodies of this fungus led to the isolation of twenty-six lanostane triterpenoids (1–26), including three undescribed ones (1–3), together with eight ergostane steroids (27–34). The structures of three new lanostane triterpenoids were elucidated as lanosta-7,9(11)-dien-3β-acetyloxy-24,25-diol (1), lanosta-7,9(11)-dien-3-oxo-24,26-diol-25-methoxy (2), and lanosta-8,20(22)-dien-3,11,23-trioxo-7β,15β-diol-26-oic acid methyl ester (3) by the analysis of 1D, 2D NMR, and HRESIMS spectroscopic data. All isolates were assayed for their cytotoxic activities using three human cancer cell lines (K562, BEL-7402, and SGC-7901) and seven lanostane triterpenoids (1, 2, 7, 13, 18, 22, and 24), and one ergostane steroid (34) showed definite cytotoxicity with IC₅₀ values that ranged from 6.64 to 47.63 μg/mL. Among these cytotoxic lanostane triterpenoids, compounds 2 and 13 showed general cytotoxicity against three human cancer cell lines, while compounds 1 and 18 exhibited significant selective cytotoxicity against K562 cells with IC₅₀ values of 8.59 and 8.82 μg/mL, respectively. Furthermore, the preliminary structure–cytotoxicity relationships was proposed.     

Structure-Based Discovery and Bioactivity Evaluation of Novel Aurora-A Kinase Inhibitors as Anticancer Agents via Docking-Based Comparative Intermolecular Contacts Analysis (dbCICA)

Aurora-A kinase plays a central role in mitosis, where aberrant activation contributes to cancer by promoting cell cycle progression, genomic instability, epithelial-mesenchymal transition, and cancer stemness. Aurora-A kinase inhibitors have shown encouraging results in clinical trials but have not gained Food and Drug Administration (FDA) approval. An innovative computational workflow named Docking-based Comparative Intermolecular Contacts Analysis (dbCICA) was applied—aiming to identify novel Aurora-A kinase inhibitors—using seventy-nine reported Aurora-A kinase inhibitors to specify the best possible docking settings needed to fit into the active-site binding pocket of Aurora-A kinase crystal structure, in a process that only potent ligands contact critical binding-site spots, distinct from those occupied by less-active ligands. Optimal dbCICA models were transformed into two corresponding pharmacophores. The optimal one, in capturing active hits and discarding inactive ones, validated by receiver operating characteristic analysis, was used as a virtual in-silico search query for screening new molecules from the National Cancer Institute database. A fluorescence resonance energy transfer (FRET)-based assay was used to assess the activity of captured molecules and five promising Aurora-A kinase inhibitors were identified. The activity was next validated using a cell culture anti-proliferative assay (MTT) and revealed a most potent lead 85(NCI 14040) molecule after 72 h of incubation, scoring IC₅₀ values of 3.5–11.0 μM against PANC1 (pancreas), PC-3 (prostate), T-47D and MDA-MB-231 (breast)cancer cells, and showing favorable safety profiles (27.5 μM IC₅₀ on fibroblasts). Our results provide new clues for further development of Aurora-A kinase inhibitors as anticancer molecules.     

In Vitro Phytochemical Screening,Cytotoxicity Studies of Curcuma longa Extracts with Isolation and Characterisation of Their Isolated Compounds

The Curcuma longa plant is endowed with multiple traditional and therapeutic utilities and is here explored for its phytochemical constituents and cytotoxic potential. Turmeric rhizomes were extracted from three different solvents and screened for the presence of different phytochemical constituents, observation of which indicated that the polar solvents favoured extraction of greater versatile phytochemical constituents. These extracts were investigated for their cytotoxic potential by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on three different of cell lines including SCC-29B (oral cancer cell line), DU-145 (prostate cancer cell line) and the Vero cell line (healthy cell line/non-cancerous cell line). This assay was performed by taking three extracts from isolated curcuminoids and a pure bioactive compound bisdemethoxycurcumin (BD). Bisdemethoxycurcumin was isolated from curcuminoids and purified by column and thin-layer chromatography, and its structural characterisation was performed with different spectroscopic techniques such as FTIR, NMR (¹H Proton and ¹³C Carbon-NMR) and LC-MS. Amongst the extracts, the ethanolic extracts exhibited stronger cytotoxic potential against the oral cancer cell line (SCC-29B) with an IC₅₀value of 11.27 μg/mL, and that this was too low of a cytotoxicity against the Vero cell line. Although, curcuminoids have also shown a comparable cytotoxic potential against SCC-29B (IC₅₀ value 16.79 μg/mL), it was not as potent against the ethanolic extract, and it was even found to be cytotoxic against healthy cell lines at a very low dose. While considering the isolated compound, bisdemethoxycurcumin, it also possessed a cytotoxic potential against the prostate cancer cell line (DU-145) (IC₅₀ value of 93.28 μg/mL), but was quite safe for the healthy cell line in comparison to doxorubicin.     

Colloidal Stability and Cytotoxicity of Polydopamine-Conjugated Gold Nanorods against Prostate Cancer Cell Lines

Prostate cancer is one of the most common cancers in men. Cell invasion is an important step in the process of cancer metastasis. Herein, gold nanorods (GNRs) and polyethylene glycol (PEG)-coated GNRs were conjugated with polydopamine (PDA). The PDA-nanoconjugates demonstrated excellent colloidal stability upon lyophilization and dispersion in cell culture media with or without the addition of fetal bovine albumin (FBS), compared to unconjugated GNRs. PDA-nanoconjugates exhibited a considerable cytotoxicity against DU-145 and PC3 prostate cancer cell lines over a concentration range of 48 μg/mL–12 μg/mL, while they were biocompatible over a concentration range of 3.0 μg/mL–0.185 μg/mL. Furthermore, PDA-nanoconjugates demonstrated possible anti-invasion activity towards prostate cancer cell lines, particularly DU-145 cell line, by reducing cell migration and cell adhesion properties. The PDA-nanoconjugates could be considered a promising nano-platform toward cancer treatment by reducing the invasion activity; it could also be considered a drug delivery system for chemotherapeutic agents.     

LC-MS/MS-Based Metabolomic Profiling of Constituents from Glochidion velutinum and Its Activity against Cancer Cell Lines

This study aimed to establish the phytochemical profile of Glochidion velutinum and its cytotoxic activity against prostate cancer (PC-3) and breast cancer (MCF-7) cell lines. The phytochemical composition of G. velutinum leaf extract and its fractions was established with the help of total phenolic and flavonoid contents and LC-MS/MS-based metabolomics analysis. The crude methanolic extract and its fractions were studied for pharmacological activity against PC-3 and MCF-7 cell lines using the MTT assay. The total phenolic content of the crude extract and its fractions ranged from 44 to 859 µg GAE/mg of sample whereas total flavonoid contents ranged from 20 to 315 µg QE/mg of sample. A total of forty-eight compounds were tentatively dereplicated in the extract and its fractions. These phytochemicals included benzoic acid derivatives, flavans, flavones, O-methylated flavonoids, flavonoid O- and C-glycosides, pyranocoumarins, hydrolysable tannins, carbohydrate conjugates, fatty acids, coumarin glycosides, monoterpenoids, diterpenoids, and terpene glycosides. The crude extract (IC₅₀ = 89 µg/mL), the chloroform fraction (IC₅₀ = 27 µg/mL), and the water fraction (IC₅₀ = 36 µg/mL) were found to be active against the PC-3 cell line. However, the crude extract (IC₅₀ = 431 µg/mL), the chloroform fraction (IC₅₀ = 222 µg/mL), and the ethyl acetate fraction (IC₅₀ = 226 µg/mL) have shown prominent activity against breast cancer cells. Moreover, G. velutinum extract and its fractions presented negligible toxicity to normal macrophages at the maximum tested dose (600 µg/mL). Among the compounds identified through LC-MS/MS-based metabolomics analysis, epigallocatechin gallate, ellagic acid, isovitexin, and rutin were reported to have anticancer activity against both prostate and breast cancer cell lines and might be responsible for the cytotoxic activities of G. velutinum extract and its bioactive fractions.