Cancer Cell Line A549 Research Articles

N-(2-ozoazepan-3-yl)-pyrrolidine-2-carboxamide, a novel Octopus vulgaris ink-derived metabolite, exhibits a pro-apoptotic effect on A549 cancer cell line and inhibits pro-inflammatory markers.

This research aimed to chemically synthesize and evaluate the antiproliferative and anti-inflammatory potential of ozopromide (OPC), a novel compound recently isolated from O. vulgaris ink. After chemical synthesis, OPC structural characterization was confirmed by COSY2D, FTIR, and C-/H-NMR. OPC inhibited the growth of human breast (MDA-MB-231), prostate (22Rv1), cervix (HeLa), and lung (A549) cancerous cells, being the highest effect on the latter (IC50: 53.70μM). As confirmed by flow cytometry, OPC induced typical apoptosis-derived morphological features on A549cells, mostly at early and late apoptosis stages. OPC generated a dose-dependent effect inhibiting IL-6 and IL-8 on LPS-stimulated peripheral mononuclear cells (PBMCs). A major affinity of OPC to Akt-1 and Bcl-2 proteins in silico agreed with the observed pro-apoptotic mechanisms. Results suggested that OPC has the potential to alleviate inflammation and be further studied for anticancer activity. Marine-derived food products such as ink contains bioactive metabolites exhibiting potential health benefits.

Novel 5-bromoindole-2-carboxylic Acid Derivatives as EGFR Inhibitors: Synthesis, Docking Study, and Structure Activity Relationship.

The indole backbone is encountered in a class of N-heterocyclic compounds with physiological and pharmacological effects such as anti-cancer, anti-diabetic, and anti-HIV. These compounds are becoming increasingly popular in organic, medicinal, and pharmaceutical research. Nitrogen compounds' hydrogen bonding, dipole- dipole interactions, hydrophobic effects, Van der Waals forces, and stacking interactions have increased their relevance in pharmaceutical chemistry due to their improved solubility. Indole derivatives, such as carbothioamide, oxadiazole, and triazole, have been reported to act as anti-cancer drugs due to their ability to disrupt the mitotic spindle and prevent human cancer cell proliferation, expansion, and invasion. To synthesize new 5-bromoindole-2-carboxylic acid derivatives that function as EGFR tyrosine kinase inhibitors as deduced through molecular docking studies. Different derivatives of indole (carbothioamide, oxadiazole, tetrahydro pyridazine-3,6-dione, and triazole) were synthesized and evaluated through different chemical, spectroscopic methods (IR, 1HNMR, 13CNMR, and MS) and assessed in silico and in vitro for their antiproliferative activities against A549, HepG2, and MCF-7 cancer cell lines. According to molecular docking analyses, compounds 3a, 3b, 3f, and 7 exhibited the strongest EGFR tyrosine kinase domain binding energies. In comparison to erlotinib, which displayed some hepatotoxicity, all of the evaluated ligands displayed good in silico absorption levels, did not appear to be cytochrome P450 inhibitors, and were not hepatotoxic. The new indole derivatives were found to decrease cell growth of three different types of human cancer cell lines (HepG2, A549, and MCF-7), with compound 3a being the most powerful while still being cancer-specific. Cell cycle arrest and the activation of apoptosis were the results of compound 3a's inhibition of EGFR tyrosine kinase activity. The novel indole derivatives, compound 3a in particular, are promising anti-cancer agents which inhibit cell proliferation by inhibiting EGFR tyrosine kinase activity.

MAPK11 (p38β) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study

MAPKs are among the most relevant signalling pathways involved in coordinating cell responses to different stimuli. This group includes p38MAPKs, constituted by 4 different proteins with a high sequence homology: MAPK14 (p38α), MAPK11 (p38β), MAPK12 (p38γ) and MAPK13 (p38δ). Despite their high similarity, each member shows unique expression patterns and even exclusive functions. Thus, analysing protein-specific functions of MAPK members is necessary to unequivocally uncover the roles of this signalling pathway. Here, we investigate the possible role of MAPK11 in the cell response to ionizing radiation (IR).We developed MAPK11/14 knockdown through shRNA and CRISPR interference gene perturbation approaches and analysed the downstream effects on cell responses to ionizing radiation in A549, HCT-116 and MCF-7 cancer cell lines. Specifically, we assessed IR toxicity by clonogenic assays; DNA damage response activity by immunocytochemistry; apoptosis and cell cycle by flow cytometry (Annexin V and propidium iodide, respectively); DNA repair by comet assay; and senescence induction by both X-Gal staining and gene expression of senescence-associated genes by RT-qPCR.Our findings demonstrate a critical role of MAPK11 in the cellular response to IR by controlling the associated senescent phenotype, and without observable effects on DNA damage response, apoptosis, cell cycle or DNA damage repair.Our results highlight MAPK11 as a novel mediator of the cellular response to ionizing radiation through the control exerted onto IR-associated senescence.

Cyclic Ruthenium-Peptide Conjugates as Integrin-Targeting Phototherapeutic Prodrugs for the Treatment of Brain Tumors.

To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Ph2phen)2(OH2)2]2+, was conjugated to the RGD-containing Ac-MRGDH-NH2 peptide by direct coordination of the M and H residues to the metal. This design afforded two diastereoisomers of a cyclic metallopeptide, Λ-[1]Cl2 and Δ-[1]Cl2. In the dark, the ruthenium-chelating peptide had a triple action. First, it prevented other biomolecules from coordinating with the metal center. Second, its hydrophilicity made [1]Cl2 amphiphilic so that it self-assembled in culture medium into nanoparticles. Third, it acted as a tumor-targeting motif by strongly binding to the integrin (Kd = 0.061 μM for the binding of Λ-[1]Cl2 to αIIbβ3), which resulted in the receptor-mediated uptake of the conjugate in vitro. Phototoxicity studies in two-dimensional (2D) monolayers of A549, U87MG, and PC-3 human cancer cell lines and U87MG three-dimensional (3D) tumor spheroids showed that the two isomers of [1]Cl2 were strongly phototoxic, with photoindexes up to 17. Mechanistic studies indicated that such phototoxicity was due to a combination of photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) effects, resulting from both reactive oxygen species generation and peptide photosubstitution. Finally, in vivo studies in a subcutaneous U87MG glioblastoma mice model showed that [1]Cl2 efficiently accumulated in the tumor 12 h after injection, where green light irradiation generated a stronger tumoricidal effect than a nontargeted analogue ruthenium complex [2]Cl2. Considering the absence of systemic toxicity for the treated mice, these results demonstrate the high potential of light-sensitive integrin-targeted ruthenium-based anticancer compounds for the treatment of brain cancer in vivo.

Prospective in vitro A431 cell line anticancer efficacy of zirconia nanoflakes derived from Enicostemma littorale aqueous extract.

Biomedical applications of zirconia nanomaterials were limited in biological systems. In this research, 8-15 nm size zirconia nanoflakes (ZrNFs) were fabricated and their nature, morphology, and biocompatibility were evaluated. The synthesis was carried out using Enicostemma littorale plant extract as an effective reducing and capping agent. Physiochemical properties of prepared ZrNFs were characterized using diverse instrumental studies such as UV-vis spectrophotometer, Fourier-transform infrared, powder X-ray diffractometer, scanning electron microscope, transmission electron microscope (TEM), energy dispersive X-ray, and cyclic voltammetry (CV). The XRD pattern confirmed the tetragonal phases of ZrNFs and the highest crystallite size of Zr0.02, Zr0.02, and Zr0.06 was 56, 50, and 44 nm, respectively. The morphology of samples was assessed using TEM. Electrophysiological effects of ZrNFs in the cellular interaction process were revealed by the slower rate of electron transfer results in CV demonstration. Biocompatibility of synthesized ZrNFs was studied on A431 human epidermoid carcinoma epithelial cells. The cell viability was increased with an increasing the concentration of nanoflakes up to 6.50-100 μg/mL. The cell viability and observed IC50 values (44.25, 36.49, and 39.62 μg/mL) reveals that the synthesized ZrNFs using E. littorale extract is found to be efficient toxic to A431 cancer cell lines.

Phytochemical profiling, antimicrobial and anticancer potential of Rosmarinus officinalis growing in Kashmir Himalayan region

Currently, medicinal plants are gaining importance in pharmaceutical and scientific communities. Medicinal plants are the most abundant natural source of valuable phytochemicals, which can help treat human diseases. The present study aimed to do phytochemical profiling and assess the antimicrobial and anticancer activity of the methanolic leaf extract of Rosmarinus officinalis. The photochemical profiling of R. officinalis leaves was done by GC-MS analysis. Twenty-six compounds were identified from the leaf extracts with great significance in pharmaceutical science for therapeutically efficient formulations to combat various diseases. The antimicrobial activity was done by the well diffusion method, while the anticancer potential against the A549 lung cancer cell line by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The highest zone of inhibition was seen against Escherichia coli ATCC 11229 (21 ± 0.7 mm), Enterococcus faecalis ATCC 29212 (19 ± 0.8 mm), Candida albicans ATCC 10231 (18± 0.6 mm) followed by Staphylococcus aureus ATCC 25923 (18 ± 0.8 mm) and Pseudomonas aeruginosa (11 ± 0.5 mm) with MIC values ranging from 128 to 256 µg/mL. R. officinalis demonstrated significant (p ≤ 0.05) anticancer activity against the A549 cancer cell line with IC50 values of 39.70 and 33.60 µg/mL for 24 and 48 hours, respectively. The methanolic extract of R. officinalis can be a potential antimicrobial and anticancer agent and a vital resource for developing new drugs.

In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives.

This study demonstrates high drug-loading of novel pyridine derivatives (S1-S4) in lipid- and polymer-based core-shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation technique and characterized for particle size, surface morphology, and entrapment efficiency. The prepared nanocapsules exhibited a particle size ranging from 185.0 ± 17.4 to 223.0 ± 15.3 nm and a drug entrapment of >90%. The microscopic evaluation demonstrated spherical-shaped nanocapsules with distinct core-shell structures. The in vitro release study depicted a biphasic and sustained release pattern of test compounds from the nanocapsules. In addition, it was obvious from the cytotoxicity studies that the nanocapsules showed superior cytotoxicity against both MCF-7 and A549 cancer cell lines, as manifested by a significant decrease in the IC50 value compared to free test compounds. The in vivo antitumor efficacy of the optimized nanocapsule formulation (S4-loaded LPNCs) was investigated in an Ehrlich ascites carcinoma (EAC) solid tumor-bearing mice model. Interestingly, the entrapment of the test compound (S4) within LPNCs remarkably triggered superior tumor growth inhibition when compared with either free S4 or the standard anticancer drug 5-fluorouracil. Such enhanced in vivo antitumor activity was accompanied by a remarkable increase in animal life span. Furthermore, the S4-loaded LPNC formulation was tolerated well by treated animals, as evidenced by the absence of any signs of acute toxicity or alterations in biochemical markers of liver and kidney functions. Collectively, our findings clearly underscore the therapeutic potential of S4-loaded LPNCs over free S4 in conquering EAC solid tumors, presumably via granting efficient delivery of adequate concentrations of the entrapped drug to the target site.

Exploring Pyrrolo-Fused Heterocycles as Promising Anticancer Agents: An Integrated Synthetic, Biological, and Computational Approach.

Five new series of pyrrolo-fused heterocycles were designed through a scaffold hybridization strategy as analogs of the well-known microtubule inhibitor phenstatin. Compounds were synthesized using the 1,3-dipolar cycloaddition of cycloimmonium N-ylides to ethyl propiolate as a key step. Selected compounds were then evaluated for anticancer activity and ability to inhibit tubulin polymerization in vitro. Notably, pyrrolo[1,2-a]quinoline 10a was active on most tested cell lines, performing better than control phenstatin in several cases, most notably on renal cancer cell line A498 (GI50 27 nM), while inhibiting tubulin polymerization in vitro. In addition, this compound was predicted to have a promising ADMET profile. The molecular details of the interaction between compound 10a and tubulin were investigated through in silico docking experiments, followed by molecular dynamics simulations and configurational entropy calculations. Of note, we found that some of the initially predicted interactions from docking experiments were not stable during molecular dynamics simulations, but that configurational entropy loss was similar in all three cases. Our results suggest that for compound 10a, docking experiments alone are not sufficient for the adequate description of interaction details in terms of target binding, which makes subsequent scaffold optimization more difficult and ultimately hinders drug design. Taken together, these results could help shape novel potent antiproliferative compounds with pyrrolo-fused heterocyclic cores, especially from an in silico methodological perspective.

Comparative Study on Biological Activities and Chemical Profiling of Mushroom (Pleurotus pulmonarius (Fr.) Quel.) Cultured on Lignocellulosic Agro Wastes.

The relevance of the lignocellulosic substrate in the cultivation of mushrooms has lent support to the exploration of several lignocellulosic agro wastes. This study was, thus, aimed at the evaluation of durian peel as an alternative substrate for more sustainable mushroom cultivation and climate change mitigation. The secondary metabolites and biological activities of both aqueous and organic mushroom (Pleurotus pulmonarius (Fr.) Quel.) extract cultured on durian peel and rubberwood sawdust substrate were compared using GCMS, LCMS as well as various biological assays (cytotoxicity, antimicrobial and antioxidant activities). Mushroom extracts from durian peel substrates possess remarkable biological activities. The results showed that the aqueous extracts had poor antimicrobial activities. The organic extracts were more active against cancer cells than the aqueous extracts, while the aqueous extracts were more potent as antioxidants than the organic extracts. Overall, the mushroom extract from the durian substrate was the most effective except against A549 and SW948, while the aqueous extract from the durian substrate was the most effective against the A549 cancer cell lines with 29.53±2.39 % inhibition. On the other hand, the organic mushroom extract from the sawdust substrate was the most effective against SW948 with 60.24±2.45 % inhibition. Further studies, however, are needed to elucidate the molecular mechanism of action of P. pulmonarius extracts against cancer cell proliferation and the effect of the substrates on the nutritional composition, secondary metabolites, and other biological activities of P. pulmonarius extracts.

Photocatalytic, antioxidant and biological activities of Alternantherasessilis (Linn.) leaf aqueous extract mediated ““Ag-Cu””bimetallic nanoparticles

In this study, “Ag-Cu” Nano composite (Bimetallic Nanoparticles) were synthesized using an aqueous extract of Alternanthera sessilis(Linn.) leaf. Biological synthesis of Bimetallic Nanoparticles has gained popularity due to its eco-friendly, cost-effective, and safe characteristics. FTIR and EDX analysis confirmed that phytochemicals present in the leaf extract played a crucial role in reducing and stabilizing the “Ag-Cu”Bimetallic Nanoparticles, which was supported by the observed zeta potential value of −31 mV, indicating the formation of stable Bimetallic Nanoparticles. XRD analysis revealed that the biogenic “Ag-Cu”Bimetallic Nanoparticles possessed a crystalline face-centered cubic (FCC) structure. TEM analysis displayed spherical Bimetallic Nanoparticles with an average size of approximately 30 nm. The “Ag-Cu”Bimetallic Nanoparticles exhibited significant photocatalytic activity against various dyes, including Eosin Y, Crystal Violet, Methylene Blue, Rhodamine B, and Methyl Orange, with degradation percentages of 98%, 94%, 97%, 93.6%, and 95% respectively after 60 min. Moreover, the biogenic “Ag-Cu”Bimetallic Nanoparticles demonstrated intriguing dose-dependent antioxidant activity, with an ABTS IC50% value of 123.86 μg/mL and the highest activity recorded at 200 μg/mL, as 70.02%. Furthermore, the “Ag-Cu”Bimetallic Nanoparticles displayed enhanced efficacy against Gram-negative bacteria compared to Gram-positive bacteria, resulting in a Zone of Inhibition against E. coli, K. pneumoniae, B. subtilis, and S. aureus, measuring 14 mm, 19 mm, 21 mm, and 15 mm respectively. Additionally, the Bimetallic Nanoparticles exhibited the highest anticancer activity at a concentration of 100 µg/mL against HeLacancer cells and A549cancer cell lines, resulting in cell viability percentages of 90% and 92% respectively.

In vitro effects of undifferentiated callus extracts from Plantago major L, Rhodiola rosea L and Silybum marianum L in normal and malignant human skin cells

Background and objectivesThe occurrence of non-melanoma and melanoma skin cancers is currently increasing rapidly with one in every three cancers diagnosed as a skin cancer. A useful strategy to control the progression of skin cancer could be the use of plant flavonoids that suppress pro-inflammatory cytokines involved in tumor initiation and progression. In this study, the anti-inflammatory and antioxidant activity of undifferentiated callus extracts from Plantago major L, Silybum marianum L and Rhodiola rosea L was investigated both in normal and malignant skin cells. MethodsAntioxidant activity of the extracts was analyzed by using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. High-Performance Thin-Layer Chromatography (HPTLC) was performed to demonstrate the phytochemical profile, and the total flavonoid content was analyzed with an aluminum chloride colorimetric method. The anti-inflammatory effect was investigated by cell treatments using the plant extracts. Thereafter, the possible suppression of induced IL-6 response was measured from the cultured skin cancer cell lines A2058 and A431, and normal primary keratinocytes with Enzyme-Linked Immunosorbent Assay (ELISA). ResultsThe HPTLC analysis assessed that the extracts contained a complex phytochemical profile that was rich in phenolic and flavonoid compounds. Dose response assays showed that concentrations between 15 and 125 μg/mL of all three plant extracts could be used to investigate an effect on the IL-6 production. The S. marianum extract had the most pronounced anti-inflammatory effect, which significantly inhibited induced IL-6 production in both normal keratinocytes and skin cells derived from epidermal carcinoma. The extract from S. marianum also had the highest flavonoid content and showed the highest antioxidant activity of the three extracts tested. ConclusionAll in all, we have confirmed that undifferentiated callus extracts of S. marianum possess properties such as antioxidant and anti-inflammatory activities in both normal and malignant keratinocytes, and thus could be a promising agent controlling the pro-inflammatory IL-6 production.

Synthesis, characterizations, antitumor and antimicrobial evaluations of novel Mn(II) and Cu(II) complexes with NNN-tridentate s-Triazine-Schiff base ligand

The new s-triazine hydrazone, 2,4-bis(morpholin-4-yl)-6-[(E)-2-[1-(pyridin-2-yl)ethylidene]hydrazin-1-yl]-1,3,5-triazine, (L) ligand was used to synthesize three new metal complexes. Single-crystal X-ray diffraction analysis indicated that the [MnLCl2] (1) and [CuLCl2].H2O (2) complexes exhibit distorted trigonal bipyramidal coordination geometry with one NNN-tridentate ligand L and two chloride ions. The trigonality index (τ5) was calculated to be 0.332 and 0.235 Ǻ for complexes 1 and 2, respectively. In case of the [CuL(NO3)2] complex (3), the Cu(II) ion is hexa-coordinated with one NNN-tridentate ligand L, one bidentate nitrate and one monodentate nitrate. The supramolecular structure of complexes 1 and 3 was analyzed using Hirshfeld calculations; hydrogen bonding-based interactions have the largest contribution in their molecular packing. The anticancer and antimicrobial activities of the ligand and its complexes (1–3) were examined. The three complexes have higher anticancer activity against colon HCT-116 and lung A-549 cancer cell lines than the free ligand (L). The only exception is complex 1 which has less cytotoxic activity against lung A-549 cancer cell line than L. Interestingly, the Cu(II) complexes have higher cytotoxic activity than the Mn(II) complex, where complex 3 has the best anticancer activity against HCT-116 (IC50 = 7.78 ± 0.27 μg/mL) and A-549 (12.40 ± 0.54 μg/mL) cell lines. In addition, the three complexes showed greater activity against gram-positive bacteria (S. aureus and B. subtilis) than gram-negative bacteria (E. coli and P. vulgaris) where 3 has best antibacterial activity.

Effects of the PARP inhibitor Niraparib on the radiosensitivity of human lung and cervical cancer cells

ObjectiveTo investigate the effect of Niraparib, a clinically approved PARP inhibitor on the radiosensitivity of human lung and cervical cancer cells, and preliminarily explore the underlying mechanism. MethodsThe human lung cancer cell line A549 and human cervical cancer cell line Siha were both treated with Niraparib for 1 ​h, or X-ray irradiation with 4 ​Gy, or Niraparib for 1 ​h combined with X-ray irradiation with 4 ​Gy. The effect was examined via measurements of cell proliferation by the cell counting kit-8 assay, and cell viability was detected by clone formation assays. Cell apoptosis and cell cycle distribution were investigated by flow cytometry. ResultsIn human lung and cervical cancer cell lines, Niraparib combined with radiation therapy significantly inhibited cell proliferation. The proportion of apoptotic cells in cell lines treated with Niraparib plus radiation (the combination group) was significantly higher compared with control, radiation, and Niraparib groups (P ​< ​0.05). Additionally, the proportion of A549 ​cells in the G2/M phase was significantly increased in the combination group compared with the radiation group (P ​< ​0.05). ConclusionPARP inhibitor Niraparib increases the radiosensitivity of tumorcells, promotes their apoptosis, and induces cell cycle redistribution. The possible mechanism is associated with the inhibition of radiation-induced DNA damage repair.

A strategy for the treatment of non-small-cell lung cancer by Ag nanoparticles

This work describes an eco-friendly approach for the green formulation of Ag nanoparticles by Allium ampeloprasum extract, without using any toxic reducing and capping agents. The morphology, structure, and physicochemical properties were characterized by several analytical techniques such as fourier transformed infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and Ultraviolet–visible spectroscopy (UV–Vis). The nanoparticles were explored biologically in the anticancer assays. Exposure of the nanoparticles samples to non-small-cell lung cancer cells resulted in cell death, which was mostly due to necrosis but slightly due to late apoptosis. The viability of malignant cell lines reduced dose-dependently in the presence of nanoparticles. The IC50 of nanoparticles were 301, 266, 255, and 250 µg/mL against EKVX, HOP-62, A549 and NCI-H460 cancer cell lines, respectively. The green-synthesized nanoparticles induced cell death, suggesting anticancer prospects that may offer new insight into the development of an anticancer nanomedicine.

Role of Extracted Nano-metal Oxides From Factory Wastes In Medical Applications

Nanometal oxides were extracted from cement factories wastes and were employed to proliferate skin cancer cells using MTT (Methyl Thiazolyl Tetraolium) assay. MTT assay results for skin cancer cell line A375,for CaO NPs the best concentration was 200 μg/mL,The viability was reduced to 57.28% while the IC50 was (69.66) g/mL for A375 and normal cell WRL68 was significantly higher (231.2 g/mL). The cytotoxicity results of CaO: MgO: Fe2O3 NPs, at higher concentrations (200 and 400) μg/mL showed a significant difference. The IC50 was (106.4) μg/mL for A375and normal cell WRL68 was significantly higher (173.3) μg/ml CaO:MgO:Fe2O3 NPs. The nanometal oxides, calcium oxide (CaO) and the mixture (CaO:MgO: Fe2O3) were extracted from wastes of cement factory, and then they were oxidized at a temperature of 400C° for (5) hours. The structural and surface properties of the prepared oxides were characterized by X-ray diffraction patterns,FE-SEM and FTIR. The X-ray data reflected that all the oxides have a polycrystalline cubic structure, with a preferred orientation along (111) for calcium oxide, with a preferred orientation along (002) for calcium oxide: magnesium oxide: iron oxide.

Diketopiperazine and isoindolinone alkaloids from the endophytic fungus Aspergillus sp. HAB10R12

Four previously undescribed alkaloids, aspergillinine A–D, and four known diterpene pyrones were isolated from the potato dextrose agar (PDA) culture of Aspergillus sp. HAB10R12. The chemical structures of the isolated compounds were elucidated based on a detailed analysis of their NMR and MS data. The absolute configuration of the isolated compounds was determined by Electronic Circular Dichroism analysis coupled with computational methods. Aspergillinine A represents the first example of a diketopiperazine dipeptide containing the unnatural amino acid N-methyl kynurenine. Its absolute configuration revealed that it adopts a rather unusual conformation. Aspergillinine B represents a previously unencountered skeleton containing an isoindolinone ring. Aspergillinine C and D were similar to previously isolated diketopiperazine alkaloids, namely, lumpidin and brevianamide F, respectively. The diterpene pyrones were isolated twice previously, once from a soil-derived Aspergillus species, and once from the liquid culture of Aspergillus sp. HAB10R12. The alkaloids isolated in this study showed no antiproliferative activity when tested against HepG2 and A549 cancer cell lines.

Evolution of Gold and Iron Oxide Nanoparticles in Conjugates with Methotrexate: Synthesis and Anticancer Effects.

Au and Fe nanoparticles and their conjugates with the drug methotrexate were obtained by an environmentally safe method of metal-vapor synthesis (MVS). The materials were characterized by transmission and scanning electron microscopy (TEM, SEM), X-ray photoelectron spectroscopy (XPS), and small-angle X-ray scattering using synchrotron radiation (SAXS). The use of acetone as an organic reagent in the MVS makes it possible to obtain Au and Fe particles with an average size of 8.3 and 1.8 nm, respectively, which was established by TEM. It was found that Au, both in the NPs and the composite with methotrexate, was in the Au0, Au+ and Au3+ states. The Au 4f spectra for Au-containing systems are very close. The effect of methotrexate was manifested in a slight decrease in the proportion of the Au0 state-from 0.81 to 0.76. In the Fe NPs, the main state is the Fe3+ state, and the Fe2+ state is also present in a small amount. The analysis of samples by SAXS registered highly heterogeneous populations of metal nanoparticles coexisting with a wide proportion of large aggregates, the number of which increased significantly in the presence of methotrexate. For Au conjugates with methotrexate, a very wide asymmetric fraction with sizes up to 60 nm and a maximum of ~4 nm has been registered. In the case of Fe, the main fraction consists of particles with a radius of 4.6 nm. The main fraction consists of aggregates up to 10 nm. The size of the aggregates varies in the range of 20-50 nm. In the presence of methotrexate, the number of aggregates increases. The cytotoxicity and anticancer activity of the obtained nanomaterials were determined by MTT and NR assays. Fe conjugates with methotrexate showed the highest toxicity against the lung adenocarcinoma cell line and Au nanoparticles loaded with methotrexate affected the human colon adenocarcinoma cell line. Both conjugates displayed lysosome-specific toxicity against the A549 cancer cell line after 120 h of culture. The obtained materials may be promising for the creation of improved agents for cancer treatment.

Design, synthesis and antitumor activity of new naproxen based 1,2,4-triazole-Schiff base derivatives

In the present work, new Naproxen based 1,2,4-triazole-Schiff base derivatives have been synthesized and screened for in vitro antitumor activity and in silico pharmacokinetic studies. The structure of the newly synthesized compounds (5–12) was elucidated by IR, NMR and mass spectrometry. All the compounds were tested against breast MCF-7, hepatocellular Huh-7 and lung A-549 cancer cell lines using MTT assay. Compound 7 was better in killing A549 cells with IC50 3.71 µM (1.48 fold), compared with Doxorubicin (IC50 5.50 µM). Also, compound 7 was found to be non toxic on MRC-5 normal cells as it depicts IC50 more than 500 μM. Besides, compound 12 also revealed promising activity with IC50 6.94 and 3.33 µM against MCF-7 and Huh-7 respectively. The in silico studies displayed that the synthesized compounds favors the desired pharmacokinetic profile and drug likeness properties. It can be concluded that these new Naproxen based 1,2,4-triazole-Schiff base derivative (7) has the potential to be further investigated as lead molecule in the development of new chemotherapeutic agent.

Determination of Some Isoquinoline Alkaloids in Extracts Obtained from Selected Plants of the Ranunculaceae, Papaveraceae and Fumarioideae Families by Liquid Chromatography and In Vitro and In Vivo Investigations of Their Cytotoxic Activity.

Alkaloids are heterocyclic bases with widespread occurrence in nature. Plants are rich and easily accessible sources of them. Most isoquinoline alkaloids have cytotoxic activity for different types of cancer, including malignant melanoma, the most aggressive type of skin cancer. The morbidity of melanoma has increased worldwide every year. For that reason, developing new candidates for anti-melanoma drugs is highly needed. The aim of this study was to investigate the alkaloid compositions of plant extracts obtained from Macleaya cordata root, stem and leaves, Pseudofumaria lutea root and herb, Lamprocapnos spectabilis root and herb, Fumaria officinalis whole plant, Thalictrum foetidum root and herb, and Meconopsis cambrica root and herb by HPLC-DAD and LC-MS/MS. For determination of cytotoxic properties, human malignant melanoma cell line A375, human Caucasian malignant melanoma cell line G-361, and human malignant melanoma cell line SK-MEL-3 were exposed in vitro to the tested plant extracts. Based on the in vitro experiments, Lamprocapnos spectabilis herb extract was selected for further, in vivo research. The toxicity of the extract obtained from Lamprocapnos spectabilis herb was tested using an animal zebrafish model in the fish embryo toxicity test (FET) for determination of the LC50 value and non-toxic doses. Determination of the influence of the investigated extract on the number of cancer cells in a living organism was performed using a zebrafish xenograft model. Determination of the contents of selected alkaloids in different plant extracts was performed using high performance liquid chromatography (HPLC) in a reverse-phase system (RP) on a Polar RP column with a mobile phase containing acetonitrile, water and ionic liquid. The presence of these alkaloids in plant extracts was confirmed by LC-MS/MS. Preliminary cytotoxic activity of all prepared plant extracts and selected alkaloid standards was examined using human skin cancer cell lines A375, G-361, and SK-MEL-3. The cytotoxicity of the investigated extract was determined in vitro by cell viability assays (MTT). For in vivo determination of investigated extract cytotoxicity, a Danio rerio larvae xenograft model was used. All investigated plant extracts in in vitro experiments exhibited high cytotoxic activity against the tested cancer cell lines. The results obtained using the Danio rerio larvae xenograft model confirmed the anticancer activity of the extract obtained from Lamprocapnos spectabilis herb. The conducted research provides a basis for future investigations of these plant extracts for potential use in the treatment of malignant melanoma.

Novel Vulgarin Derivatives: Chemical Transformation, In Silico and In Vitro Studies.

Vulgarin, an eudesmanolide sesquiterpene isolated from Artemisia judaica, was refluxed with iodine to produce two derivatives (1 and 2), which were purified and spectroscopically identified as naproxen methyl ester analogs. The reaction mechanism by which 1 and 2 were formed is explained using a sigmatropic reaction with a 1,3 shift. The scaffold hopping via lactone ring opening enabled the new derivatives of vulgarin (1 and 2) to fit well inside the COX-2 active site with ΔG of -7.73 and -7.58 kcal/mol, respectively, which was better than that of naproxen (ΔG of -7.04 kcal/mol). Moreover, molecular dynamic simulations showed that 1 was able to achieve a faster steady-state equilibrium than naproxen. The novel derivative 1 showed promising cytotoxic activities against HepG-2, HCT-116, MCF-7, and A-549 cancer cell lines compared to those of vulgarin and naproxen.