Cancer Cell Line A549 Research Articles

Investigation the Cytotoxic and Antimicrobial Effect of Ranunculus Poluninii

Ranunculus plant species, one of the endemic plants, are used in the treatment of various diseases such as febrile diseases, rheumatism and inflammatory rashes due to their pharmacological and toxicological activities. Considering these features, it was aimed to investigate the cytotoxic effects of Ranunculus poluninii on cancer cell lines, bacteria and yeasts. For this purpose, the extract of the plant was obtained by methanol extraction. Different concentrations of stock were prepared from this plant and applied to A549 and HCT116 cancer cell lines, and MTT assay was performed to determine cell viability. In addition, MIC values were determined by applying the prepared plant extract to Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, Candida albicans and Candida glabrata. Our results showed that Ranunculus poluninii was reduced cell viability to 83.7% at 100 µg/mL and 79% at 200 µg/mL on A549 and HCT116 respectively. In addition, it decreased both Candida albicans and Candida glabrata growth to 91.5% at 800 µg/m and 95.1% at 50 µg/mL respectively. Our results suggest that Ranunculus poluninii has anticancer effect and antifungal activity.

Phosphatidylcholine and ceramide derivatives from white rot fungus Microporus xanthropus PP17-20

The undescribed phosphatidylcholine (1), along with twelve known compounds, was isolated from the cultures of white rot fungus Microporus xanthropus PP17-20. In this work the fungus was cultivated in Yeast-Malt extract medium to explore active compound production. The chemical structures were elucidated on the basis of spectroscopic and HRESIMS data. Several isolated compounds were evaluated for anti-proliferative activity against A549 and MCF-7 cancer cell lines.

Novel tetraaza macrocyclic Schiff base complexes of bivalent zinc: microwave-assisted green synthesis, spectroscopic characterization, density functional theory calculations, molecular docking studies, in vitro antimicrobial and anticancer activities.

In the present manuscript, novel macrocyclic Schiff base complexes [Zn(N4MacL1)Cl2-Zn(N4MacL3)Cl2] were synthesized by the reaction of ZnCl2 and macrocyclic ligands (N4MacL1-N4MacL3) derived from diketone and diamines under microwave irradiation method and conventional method. The structures of the obtained complexes were identified by various spectrometric methods such as Fourier transformation infra-red (FT-IR), nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), powder X-ray diffraction, molar conductivity, and UV-vis. The structures of the synthesized compounds were optimized by using the def2-TZV/J and def2-SVP/J Coulomb fitting basis sets at B3LYP level in density functional theory (DFT) calculations. The macrocyclic Schiff base complexes exhibited higher activities against Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus), Gram-negative bacteria (Escherichia coli and Xanthomonas campestris), and fungal strains (Fusarium oxysporum and Candida albicans) in comparison to macrocyclic Schiff base ligands. Furthermore, the newly synthesized macrocyclic compounds were assessed for their anticancer activity against three cell lines: A549 (human alveolar adenocarcinoma epithelial cell line), HT-29 (human colorectal adenocarcinoma cell line), and MCF-7 (human breast adenocarcinoma cell line) using the MTT assay. The obtained results showed that the macrocyclic complex [Zn(N4MacL3)Cl2] displayed the highest cytotoxic activity (2.23 ± 0.25µM, 6.53 ± 0.28µM, and 7.40 ± 0.45µM for A549, HT-29, and MCF-7 cancer cell lines, respectively). Additionally, molecular docking investigations were conducted to elucidate potential molecular interactions between the synthesized macrocyclic compounds and target proteins. The results revealed a consistent agreement between the docking calculations and the experimental data.

Labdane-type diterpenoids with cytotoxic and anti-inflammatory activities from the aerial parts of Hypoestes purpurea (L.) R. Br.

Two new ent-labdane diterpenoids, hypoestesins A-B (1–2) and five new labdane diterpenoids, hypopurolides H-L (3–7), were isolated from the aerial parts of Hypoestes purpurea. All of the structures were fully determined based on extensive analysis of 1H, 13C, 2D NMR, and HRESIMS data. The absolute configurations of 1–3 was established through comparing the experimental and calculated ECD curves and the structure of 5 was confirmed by single crystal X-ray diffraction experiment. Compounds 5–7 were unusual C23 labdane diterpenoids having a γ-acetonyl-α, β-unsaturated γ-lactone unit and each assigned as C-15 epimeric mixture. Furthermore, cytotoxic and anti-inflammatory activities of 3–7 were evaluated. The results showed that 3 had remarkable cytotoxic activity against HL-60, A549, SMMC-7721, MDA-MB-231, and SW480 cancer cell lines with IC50 values ranging from 2.35 to 17.06 μM. Compound 4 showed moderate cytotoxic activity against HL-60 and SMMC-7721 cancer cell lines with IC50 values of 15.12 ± 0.53 and 12.92 ± 0.60 μM, respectively. Furthermore, compound 4 was also found to exhibit inhibitory activity against NO production in RAW 264.7 macrophages with IC50 values of 23.56 ± 0.99 μM, compared to the positive control L-NMMA with an IC50 value of 41.11 ± 1.34 μM.

Synthesis, docking studies, in silico ADMET predictions, DFT calculations, and photophysical properties of thiazole-anthracene hybrids as potent EGFR inhibitors

The thiazole ring closure of thiosemicarbazones with α-bromo-4-substituted acetophenones was carried out to generate aminothiazole analogues (A1–A16). Experimental methods were used to characterize the developed compounds, including HRMS, 1H, 13C NMR, and elemental analysis. Single-crystal XRD investigations have verified the compound A5 crystal structure. All the synthesized hybrid compounds underwent screening for their anticancer activity against various cancer cell lines, encompassing human breast adenocarcinoma (MCF-7) and human lung adenocarcinoma (A549), as well as normal human breast cell (MCF-10A). The compounds A2, A5, and A8 exhibited excellent anticancer activity against MCF-7 and A549 cancer cell lines compared to the reference drug Erlotinib. Later, in vitro, EGFR results revealed that compared to the reference drug Erlotinib (IC50 value = 0.42 ± 0.04 µM), compounds A2, A5 and A8 displayed the highest tyrosine kinase EGFR inhibitory potency with IC50 values of 1.38 ± 0.11 µM, 0.88 ± 0.05 µM and 1.86 ± 0.12 µM, respectively.Furthermore, in silico molecular docking studies on EGFR (PDB ID: 4HJ0) protein revealed that the potent ligands exhibited higher affinity with an active pocket of receptors showing strong hydrogen bond interactions. The compounds' electronic behaviour, stable geometries, MEP surfaces, and FMO analysis were investigated employing density functional theory (DFT) at the B3LYP level with a 6-311G(d, p) basic set. An in silico ADMET study was also performed to predict the pharmacokinetic and toxicity profile of synthesized compounds, which expressed good oral drug-like behaviour and non-toxic nature. Further, the photophysical properties (UV and fluorescence) of the compounds were discussed.

UPLC-Q-TOF-MS/MS-Based Targeted Discovery of Chetomin Analogues from Chaetomium cochliodes.

Chetocochliodin M (5) containing a rare cage-ring and chetocochliodin N (6) featuring an unusual piperazine-2,3-dione ring system together with known analogues chetomin (1), chetoseminudin C (2), chetocochliodin I (3), and oidioperazine E (4) were targeted for purification from the fungus Chaetomium cochliodes using a UPLC-Q-TOF-MS/MS approach. The structures of the new compounds were elucidated using HR-ESI-MS, NMR, and ECD spectra. Compounds 1, 3, and 6 exhibited strong cytotoxic activities against A549 and HeLa cancer cell lines.

Synthesis, spectroscopic characterization, biological evaluation studies on 6-methoxy-8-nitroquinolinium picrate: A potent lung cancer drug

The compound 6-Methoxy-8-Nitroquinolinium Picrate was synthesized and characterized using FT-IR, FT-Raman, and UV–Vis spectroscopic techniques. Vibrational wavenumbers were calculated and compared with experimental values, while UV–Vis analysis revealed electronic transitions within the molecule. Frontier molecular orbitals, molecular electrostatic potential surface, Mulliken atomic charge distribution, and Natural bond orbitals analyses confirmed the molecule's bioactivity and validated the intramolecular charge transfer within the molecule. Antibacterial testing exhibited activity against Klebsiella pneumoniae, while in vitro cytotoxicity experiments demonstrated higher inhibition of A549 cancer cell lines compared to HeLa cell lines. Molecular docking supported the in vitro cytotoxicity findings, suggesting the potential for developing new lung cancer treatments based on this research.

Transforming microbial pigment into therapeutic revelation: extraction and characterization of pyocyanin from Pseudomonas aeruginosa and its therapeutic potential as an antibacterial and anticancer agent

BackgroundThe objectives of the current study were to extract pyocyanin from Pseudomonas aeruginosa clinical isolates, characterize its chemical nature, and assess its biological activity against different bacteria and cancer cells. Due to its diverse bioactive properties, pyocyanin, being one of the virulence factors of P. aeruginosa, holds a promising, safe, and available therapeutic potential.Methods30 clinical P. aeruginosa isolates were collected from different sources of infections and identified by routine methods, the VITEK 2 compact system, and 16 S rRNA. The phenazine-modifying genes (phzM, phzS) were identified using polymerase chain reaction (PCR). Pyocyanin chemical characterization included UV-Vis spectrophotometry, Fourier Transform Infra-Red spectroscopy (FTIR), Gas Chromatography-Mass Spectrometry (GC-MS), and Liquid Chromatography-Mass Spectrometry (LC-MS). The biological activity of pyocyanin was explored by determining the MIC values against different clinical bacterial strains and assessing its anticancer activity against A549, MDA-MB-231, and Caco-2 cancer cell lines using cytotoxicity, wound healing and colony forming assays.ResultsAll identified isolates harboured at least one of the phzM or phzS genes. The co-presence of both genes was demonstrated in 13 isolates. The UV-VIS absorbance peaks were maxima at 215, 265, 385, and 520 nm. FTIR could identify the characteristic pyocyanin functional groups, whereas both GC-MS and LC-MS elucidated the chemical formula C11H18N2O2, with a molecular weight 210. The quadri-technical analytical approaches confirmed the chemical nature of the extracted pyocyanin. The extract showed broad-spectrum antibacterial activity, with the greatest activity against Bacillus, Staphylococcus, and Streptococcus species (MICs 31.25–125 µg/mL), followed by E. coli isolates (MICs 250–1000 µg/mL). Regarding the anticancer activity, the pyocyanin extract showed IC50 values against A549, MDA-MB-231, and Caco-2 cancer cell lines of 130, 105, and 187.9 µg/mL, respectively. Furthermore, pyocyanin has markedly suppressed colony formation and migratory abilities in these cells.ConclusionsThe extracted pyocyanin has demonstrated to be a potentially effective candidate against various bacterial infections and cancers. Hence, the current findings could contribute to producing this natural compound easily through an affordable method. Nonetheless, future studies are required to investigate pyocyanin’s effects in vivo and analyse the results of combining it with other traditional antibiotics or anticancer drugs.

The Influence of the Auxiliary Ligand in Monofunctional Pt(II) Anticancer Complexes on the DNA Backbone.

Monofunctional platinum complexes offer a promising alternative to cisplatin in cancer chemotherapy, showing a unique mechanism of action. Their ability to induce minor helix distortions effectively inhibits DNA transcription. In our study, we synthesized and characterized three monofunctional Pt(II) complexes with the general formula [Pt(en)(L)Cl]NO3, where en = ethylenediamine, and L = pyridine (py), 2-methylpyridine (2-mepy), and 2-phenylpyridine (2-phpy). The hydrolysis rates of [Pt(en)(py)Cl]NO3 (1) and [Pt(en)(2-mepy)Cl]NO3 (2) decrease with the bulkiness of the auxiliary ligand with k(1) = 2.28 ± 0.15 × 10-4 s-1 and k(2) = 8.69 ± 0.98 × 10-5 s-1 at 298 K. The complex [Pt(en)(2-phpy)Cl]Cl (3) demonstrated distinct behavior. Upon hydrolysis, an equilibrium (Keq = 0.385 mM) between the complexes [Pt(en)(2-phpy)Cl]+ and [Pt(en)(2-phpy-H+)]+ was observed with no evidence (NMR or HR-ESI-MS) for the presence of the aquated complex [Pt(en)(2-phpy)(H2O)]2+. Despite the kinetic similarities between phenanthriplatin and (2), complexes (1) and (2) exhibit minimal activity against A549 lung cancer cell line (IC50 > 100 μΜ), whereas complex (3) exhibits notable cytotoxicity (IC50 = 41.11 ± 2.1 μΜ). In examining the DNA binding of (1) and (2) to the DNA model guanosine (guo), we validated their binding through guoN7, which led to an increased population of the C3'-endo sugar conformation, as expected. However, we observed that the rapid transition 2E (C2'-endo) ↔ 3E (C3'-endo), in the case of [Pt(en)(py)(guo)](NO3)2 ([1-guo]), slows down in the case of [Pt(en)(2-mepy)(guo)](NO3)2 ([2-guo]), resulting in separate signals for the two conformers in the 1H NMR spectra. This phenomenon arises from the steric hindrance between the methyl group of pyridine and the sugar moiety of guanosine. Notably, this hindrance is absent in [2-(9-MeG)] (9-MeG = 9-methylguanine), probably due to the absence of a bulky sugar unit in 9-MeG. In the case of (3), where the bulkiness of the substitution on the pyridine is further increased by a phenyl group, we observed a notable proximity between 9-MeGH8 and the phenyl ring of 2-phpy. Considering that only (3) exhibited good cytotoxicity against the A549 cancer cell line, it is suggested that auxiliary ligands, L, with an extended aromatic system and proper orientation in complexes of the type cis-[Pt(en)(L)Cl]NO3, may enhance the cytotoxic activity of such complexes.

Synthesis, biological evaluation, and computational studies of thiazolyl hydrazone derivatives as triple mutant allosteric EGFR inhibitors

AbstractHerein, new thiazole‐2‐yl‐based hydrazone derivatives were synthesized and assessed for in vitro anticancer activity against wild type A549, MCF7, DU145, and mutant H1975 cancer cell lines by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Among all, 4‐(4‐Chlorophenyl)‐2‐(2‐((4‐methylthiazol‐5‐yl)methylene)hydrazineyl)thiazole (4b) elicited prominent anticancer activity against wild‐type epidermal growth factor receptor (WT‐EGFR) MCF7 cancer cell line with an IC50 value of 9.57 ± 1.80 μM, whereas 4‐Methyl‐5‐((2‐(4‐(4‐nitrophenyl)thiazol‐2‐yl)hydrazineylidene)methyl)thiazole (4c) showed appreciable activity with an IC50 value of 11 ± 0.7 μM against the mutated EGFR H1975 lung cancer cells. Doxorubicin and Osimertinib were used as the standard drugs for comparison of activity. Compound (4b) significantly increased early apoptosis (30.2%) and late apoptosis (7.6%) at a 5 μM concentration in comparison with the control (early apoptosis 2.5%, late apoptosis 1.2%). The molecular docking study was performed against mutant EGFR (T790M/C797S) (PDB: 5D41) enzyme to gain information about interactions of synthesized molecules with binding pockets. Moreover, ADME study and molecular dynamic simulation studies were accomplished to gain insight into drug‐likeness and conformational stability, respectively. The findings demonstrate a promising alignment between the observed anticancer effects and computational analyses.

Apoptosis inducing anti-proliferative activity of Citrullus lanatus seeds against A549 cell lines

Cancer is a leading dangerous death-causing disease in millions over the world. It arises due to the uncontrolled growth of mal-functioned cells and formed as tumors. The disease can affect any part of the body. Still, it is a quest to find anti-cancer drugs which has been the major research endeavor around the globe. Traditionally humans use plants and their derived products as a source to cure various diseases. In recent years many researches had paved the way to use plant-based drugs. The current research aims to evaluate the anticancer activity of Citrullus lanatus seeds against A549 lung carcinoma epithelial cell lines. The study uses C. lanatus seeds which naturally contains antioxidants and phytochemicals that prevent cancer cell proliferation. The ethanolic seed extract of C. lanatus showed the presence of phytochemicals such as saponins, alkaloids, proteins and flavonoids by preliminary screening. The extract was tested for its anti-inflammatory showing 96.16 % at maximum concentration. The microbial assays also showed good signs of inhibition against the microorganisms by forming a zone of inhibition. The safety and efficacy of the extract were determined by MTT assay for the cytotoxicity using A549 cancer cell lines and non-cancerous cell lines. The IC50 concentration of C. lanatus seed extract showed dosage dependently at 51.73 μg/ml for A549 cell lines. They also resulted in significant induced cell cycle arrest and apoptosis at the G2 phase by inhibiting the A549 cell line proliferation. The present study works on lung carcinoma to find a better procurement in a traditional way that can develop future hope in the pharmaceutical industry.

Comparative Study of the Potential Cell-Penetrating Peptide ∆M4 on Apoptosis Cell Signaling in A375 and A431 Cancer Cell Lines.

In recent yearsjajajj, peptide-based therapeutics have attracted increasing interest as a potential approach to cancer treatment. Peptides are characterized by high specificity and low cytotoxicity, but they cannot be considered universal drugs for all types of cancer. Of the numerous anticancer-reported peptides, both natural and synthetic, only a few have reached clinical applications. However, in most cases, the mechanism behind the anticancer activity of the peptide is not fully understood. For this reason, in this work, we investigated the effect of the novel peptide ∆M4, which has documented anticancer activity, on two human skin cancer cell lines. A novel approach to studying the potential induction of apoptosis by anticancer peptides is the use of protein microarrays. The results of the apoptosis protein study demonstrated that both cell types, skin malignant melanoma (A375) and epidermoid carcinoma (A431), exhibited markers associated with apoptosis and cellular response to oxidative stress. Additionally, ∆M4 induced concentration- and time-dependent moderate ROS production, triggering a defensive response from the cells, which showed decreased activation of cytoplasmic superoxide dismutase. However, the studied cells exhibited a differential response in catalase activity, with A375 cells showing greater resistance to the peptide action, possibly mediated by the Nrf2 pathway. Nevertheless, both cell types showed moderate activity of caspases 3/7, suggesting that they may undergo partial apoptosis, although another pathway of programmed death cannot be excluded. Extended analysis of the mechanisms of action of anticancer peptides may help determine their effectiveness in overcoming chemoresistance in cancerous cells.

Design, synthesis and apoptotic activity of substituted chalcones tethered 1,3,5-triazine hybrids: An insights from molecular docking, molecular dynamics simulations, DFT, ADME, and DAPI analyses

A novel library of chalcone tethered 1,3,5-triazine hybrids (5a-j) were designed and synthesized and their structures were confirmed by using spectroscopic/analytical techniques. The anticancer activity of the synthesized novel derivatives (5a-j) was evaluated against four human cancer cell lines: PC3 (Prostate cancer), A549 (Lung cancer), MCF7 (Breast cancer), and Colo-205 (Colon cancer) by employing of MTT assay method. In comparison to “Etoposide”, all the compounds showed excellent to moderate activity. The IC50 values of the novel derivatives (5a-j) ranged from 0.01±0.0032 µM to 12.4 ± 6.18 µM whereas positive control (Etoposide) showed 0.14±0.017 µM to 3.08±0.135 µM respectively. The newly developed substituted chalcone linked triazine hybrids were found to be good alternative anticancer agents. Among the all, (5a-j), mainly 5a, 5e, 5f, 5 g and 5j displayed highly potent anticancer activity towards MCF7 (5a), A549 (5 g), PC3 (5e, 5f) and Colo-205 (5j) human cancer cell lines. Principally, two compounds 5a and 5e were displayed as the most promising activities. The apoptotic mechanism in anticancer activity was further confirmed by nuclear staining analysis on more active test compounds 5a and 5e by DAPI (4′,6-diamidino-2-phenylindole) at different concentrations with MCF-7 cells, Additionally, all the synthesized compounds were investigated by molecular docking simulation studies with topoisomerase-IIβ enzyme (PDB ID: 3QX3) protein to correlate the in-vitro biological activity data evaluated on four human cancer cell lines. The docking scores of the newly produced conjugates (5a-j) varied from – 7.52 kcal/mol to -6.27 kcal/mol, indicating these compounds serve as an inhibitor. Human oral absorption is expected to be greater than 75 %. The in-vitro cytotoxicity behavior of tested compounds was further supported by in-silico predictions such as ADME, MD simulations and DFT studies.

Anticancer Activity of Sargassum fluitans Extracts in Different Cancer Cells.

The arrival of large quantities of Sargassum in the Mexican Caribbean Sea has generated major environmental, health and economic problems. Although Sargassum has been used in the generation of some commercial products, few studies have described its possible applications as a source of compounds with anticancer activity. This study aimed to evaluate the antiproliferative effects of different Sargassum extracts on various cancer cell lines. Furthermore, LC/QTOF-MS was used to identify the compounds related to the antiproliferative effect. First, determination of the seaweed was performed, and dichloromethane, chloroform and methanol extracts were obtained. The extracts were evaluated for their antiproliferative effects by MTT in breast (MDAMB- 231 and MCF-7), prostate (DU-145), lung (A549) and cervical (SiHa) cancer cell lines. Finally, LC/QTOFMS identified the compounds related to the antiproliferative effect. The authentication showed Sargassum fluitans as the predominant species. The extracts of dichloromethane and chloroform showed an antiproliferative effect. Interestingly, the fractionation of the chloroform extract showed two fractions (FC1 and FC2) with antiproliferative activity in MDA-MB-231, SiHa and A549 cancer cell lines. On the other hand, three fractions of dichloromethane extract (FD1, FD4 and FD5) also showed antiproliferative effects in the MDA-MB-231, MCF-7, SiHa and DU-145 cancer cell lines. Furthermore, LC/QTOF-MS revealed the presence of eight major compounds in FC2. Three compounds with evidence of anticancer activity were identified (D-linalool-3-glucoside, (3R,4S,6E,10Z)-3,4,7,11-tetramethyl-6,10-tridecadienal and alpha-tocotrienol). These findings showed that Sargassum fluitans extracts are a possible source of therapeutic agents against cancer and could act as scaffolds for new drug discovery.

Biological Activities of Ethanol Extracts of Hericium erinaceus Obtained as a Result of Optimization Analysis.

Mushrooms are one of the indispensable elements of human diets. Edible mushrooms stand out with their aroma and nutritional properties. In this study, some biological activities of the wild edible mushroom Hericium erinaceus were determined. In this context, firstly, the most suitable extraction conditions of the fungus in terms of biological activity were determined. First, 64 different experiments were performed with the Soxhlet device under 40-70 °C extraction temperature, 3-9 h extraction time, and 0.5-2 mg/mL extraction conditions. As a result, a total antioxidant status (TAS) analysis was performed, and the extraction conditions were optimized so that the objective function was the maximum TAS value. The data obtained from the experimental study were modeled with artificial neural networks (ANNs), one of the artificial intelligence methods, and optimized with a genetic algorithm (GA). All subsequent tests were performed using the extract obtained under optimum extraction conditions. The antioxidant capacity of the mushroom was assessed using Rel assay kits and the DPPH and FRAP techniques. The agar dilution method was used to measure the antimicrobial activity. The anti-Alzheimer activity was assessed based on the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The antiproliferative activity was assessed against the A549 cancer cell line. The total phenolic content was measured using the Folin-Ciocalteu reagent. The measurement of total flavonoids was conducted using the aluminum chloride test. LC-MS/MS equipment was used to screen for the presence of standard chemicals. The optimum extraction conditions were found to be a 60.667 °C temperature, 7.833 h, and 1.98 mg/mL. It was determined that the mushroom has high antioxidant potential. It was determined that the substance was successful at combating common bacterial and fungal strains when used at dosages ranging from 25 to 200 µg/mL. The high antiproliferative effect of the substance was attributed to its heightened concentration. The anti-AChE value was found to be 13.85 μg/mL, while the anti-BChE value was confirmed to be 28.00 μg/mL. The phenolic analysis of the mushroom revealed the presence of 13 chemicals. This investigation found that H. erinaceus exhibits robust biological activity when extracted under appropriate circumstances.

Discovery of new eremophilanes from the marine-derived fungus Emericellopsis maritima BC17 by culture conditions changes: evaluation of cytotoxic and antimicrobial activities

In our previous studies, the marine-derived fungus Emericellopsis maritima BC17 was found to produce new eremophilane-type sesquiterpenoids on solid media. In order to explore its potential to produce more metabolites, E. maritima BC17 was subjected to a one strain-many compounds (OSMAC) analysis leading to the discovery of three new eremophilanes (1-3) and fourteen known derivatives (4-17) in the liquid media Czapek Dox and PDB. Their structures were established by extensive analyses of the 1D and 2D NMR, and HRESIMS data, as well as ECD data for the assignment of their absolute configurations. Antitumoral and antimicrobial activities of the isolated metabolites 1, 3, 11, and 15 were investigated. PR toxin 3-deacetyl (15) exhibited cytotoxic activity against HepG2, MCF-7, A549, A2058 and Mia PaCa-2 human cancer cell lines with IC50 values ranging from 2.5 to 14.7 µM. In addition, 15 exhibited selective activity against methicillin-sensitive Staphylococcus aureus ATCC29213 at the highest concentration tested of 128 µg/mL.

Three new nonenes from culture broth of marine-derived fungus Albifimbria verrucaria and their cytotoxic and anti-viral activities.

Three new nonenes, verrucanonenes A‒C (1‒3), were isolated from culture broth of marine-derived fungus Albifimbria verrucaria. These compounds were isolated using silica gel column chromatography, reversed-phase medium pressure liquid chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were determined using a spectroscopic method. Cytotoxicities of these isolated compounds to A549, DU145, HCT116, and HT1080 cancer cell lines were assessed. Compounds 1‒3 exhibited cytotoxicities to DU145 cancer cell line, with IC50 values of 23.4, 28.6, and 20.1 µM, respectively. Compound 2 decreased H1N1-induced cytopathic effects on MDCK cells in a dose-dependent manner.

The prognostic value and immunological role of MVP in pan-cancer study.

Major Vault Protein (MVP) has emerged as a potential prognostic and immunological biomarker in various cancer types. This pan-cancer study aimed to investigate expression of MVP and its correlation with clinical outcomes and immune infiltration across diverse cancer types. We conducted an analysis of extensive transcriptomic and clinical data from publicly available databases. Our findings unveiled a significant association between MVP expression and cancer progression, with higher expression levels predicting poorer overall survival in multiple cancer types. Importantly, MVP expression demonstrated a close relationship with immune infiltration in the tumor microenvironment, showing that higher expression levels were associated with increased immune cell infiltration. We further validated expression of MVP and function in cancer cell lines A549 and AGS. These compelling results suggest that MVP holds promise as a valuable biomarker for prognostic assessment and the development of immunotherapeutic strategies across various cancer types. Consequently, targeting MVP may offer a compelling therapeutic approach in the treatment of human cancers.

Structure-bioactivity relationship study on anticancer Pd and Pt complexes with aliphatic glycine derivative ligands

To investigate the structure and bioactivity relationship, six Pd(II)/Pt(II) complexes with N-isobutylglycine (L1) and cyclohexylglycine (L2) as N^O amino acid bidentate ligands, 1,10′-phenanthroline (phen) and 2,2′-bipyridine (bipy) as N^N donor ligands, and [Pd(L1)(bipy)]NO3 (1), [Pd(L2)(bipy)]NO3 (2), [Pd(L1)(phen)]NO3 (3), [Pd(L2)(phen)]NO3·2H2O (4), [Pt(L1)(phen)]NO3 (5), along with [Pt(L2)(phen)]NO3 (6) were prepared and then characterized. The geometry of each compound was validated by doing a DFT calculation. Furthermore, tests were conducted on the complexes’ water solubilities and lipophilicity. All bipy complexes had superior aqueous solubility and less lipophilicity in comparison with phen complexes, as well as complexes containing cyclohexyl-glycine compared to isobutyl-glycine complexes, probably because of the steric effects and polarity of cyclohexylglycine. The in-vitro anticancer activities of these compounds were examined against HCT116, A549, and MCF7 cancerous cell lines. Data revealed that all Pd/Pt complexes demonstrate higher anticancer activity than carboplatin, and complexes 3 and 4 are more cytotoxic than cisplatin against the HCT116 cell line, particularly against MCF7 cancerous cells. In addition, among all compounds, complex 4 has more anticancer ability than oxaliplatin. Due to different solubility and lipophilicity behavior, the accumulation of Pt complexes and clinical Pt drugs in each cancerous cell was investigated. The binding capabilities of these complexes to DNA, as the main target in chemotherapy, occur through minor grooves and intercalate into DNA, which was done using absorption, fluorescence, and circular dichroism spectroscopy. Finally, the docking simulation study showed the mode of DNA bindings is in good agreement with the spectral binding data.

Synthesis, molecular structure and biological activity of novel bis-1,3-tropolones based on 4-chloro-2,7-dimethyl-1,8-naphthyridine

The acid-catalyzed reaction of 4-chloro-2,7-dimethyl- 1,8-naphthyridine with 4,6-di-tert-butyl-3-nitro-1,2-benzoquinone leads to new bis-1,3-tropolones. The crystal structures of the obtained bis-1,3-tropolones were determined by X-ray diffraction analysis; the spectral and luminescent properties, the structural and energy characteristics of the compounds were examined. The cytotoxic effect in vitro against cancer cell lines A549, H1299, HT29, CT26 and B16F10 was assessed using MTT assay.