Cancer Cell Line A549 Research Articles

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.

Seco-pimarane diterpenoids and androstane steroids from an endophytic Nodulisporium fungus derived from Cyclosorus parasiticus

Five previously undescribed specialized metabolites, including three 9,11-seco-pimarane diterpenoids, nodulisporenones A–C, and two androstane steroids, nodulisporisterones A and B, together with previously described ergosterol derivatives, dankasterone A and demethylincisterol A3, were isolated from solid cultures of the endophytic fungus Nodulisporium sp. SC-J597. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and theoretical calculations of electronic circular dichroism spectra. Among them, nodulisporenones A and B are the first examples of seco-pimarane diterpenoids that is cyclized to form an unprecedented diterpenoid lactone scaffold and nodulisporisterones A and B represent the first normal C19 androstane steroids of fungal origin. Nodulisporisterone B exhibited potent inhibitory effect on the production of NO in LPS-stimulated RAW264.7 macrophages (IC50 = 2.95 μM). This compound, together with the two known ergosterol derivatives, also displayed cytotoxicity against A549, HeLa, HepG2 and MCF-7 cancer cell lines with IC50 values of 5.2–16.9 μM.

Phytochemicals constituents, antioxidant activities and cytotoxicity assays of few wild edible fruits of North-East India

ABSTRACT Wild edible fruits are found globally and play multifarious functions. The present study was undertaken to study the antioxidants and anti-cancerous potential of six wild edible fruits from Mizoram viz. Garcinia lanceifolia, Embelia subcoriacea, Elaeocarpus tectorius, Elaeagnus caudata, Cissus obovata and Averrhoa carambola. The fruits were identified through ITS1 and ITS2 partial genes and the sequences were submitted to GenBank depository and NCBI databases. Physical and physico-chemical characteristics were assessed for their importance. The phytochemical content of the fruits was analyzed qualitatively and shown the presence of saponin, flavonoids, tannin, cardiac glycosides, alkaloids and terpenoids. The extracts were then subjected to quantification of secondary metabolites, such as gallic acid, rutin and quercetin. Further, secondary metabolites, such as gallic acid, rutin, quercetin, hesperidin and naringin were quantified by the HPLC method, which showed significantly high quantity from the extracts. The free radical scavenging activity performed using DPPH and ABTS cations revealed that the extracts possess high potency for scavenging properties, with IC50 ranging from 10.37 to 567.8 µg ml−1. The cytotoxicity of the extracts assessed against A549 cancer cell line showed potency, with IC50 value ranging from 18.2 to 203.2 µg ml−1. Therefore, the present study revealed that wild edible fruits could be a good resource for ethno-medicine as well as income generation for the local people of Mizoram, north-east India.

Overexpression of Pericentromeric HSAT2 DNA Increases Expression of EMT Markers in Human Epithelial Cancer Cell Lines.

Pericentromeric tandemly repeated DNA of human satellites 1, 2, and 3 (HS1, HS2, and HS3) is actively transcribed in some cells. However, the functionality of the transcription remains obscure. Studies in this area have been hampered by the absence of a gapless genome assembly. The aim of our study was to map a transcript that we have previously described as HS2/HS3 on chromosomes using a newly published gapless genome assembly T2T-CHM13, and create a plasmid overexpressing the transcript to assess the influence of HS2/HS3 transcription on cancer cells. We report here that the sequence of the transcript is tandemly repeated on nine chromosomes (1, 2, 7, 9, 10, 16, 17, 22, and Y). A detailed analysis of its genomic localization and annotation in the T2T-CHM13 assembly revealed that the sequence belonged to HSAT2 (HS2) but not to the HS3 family of tandemly repeated DNA. The transcript was found on both strands of HSAT2 arrays. The overexpression of the HSAT2 transcript increased the transcription of the genes encoding the proteins involved in the epithelial-to-mesenchymal transition, EMT (SNAI1, ZEB1, and SNAI2), and the genes that mark cancer-associated fibroblasts (VIM, COL1A1, COL11A1, and ACTA2) in cancer cell lines A549 and HeLa. Co-transfection of the overexpression plasmid and antisense nucleotides eliminated the transcription of EMT genes observed after HSAT2 overexpression. Antisense oligonucleotides also decreased transcription of the EMT genes induced by tumor growth factor beta 1 (TGFβ1). Thus, our study suggests HSAT2 lncRNA transcribed from the pericentromeric tandemly repeated DNA is involved in EMT regulation in cancer cells.

Synthesis and Characterization of 8-Amino-6-Methoxy Quinolinium 2,4-Dinitrophenolate: DFT, Molecular Docking, Antimicrobial, and In Vitro Cytotoxicity Evaluation Studies

Quinoline and its derivatives are well recognized for their anticancer activities and pharmacological properties. In this work, the compound 8-Amino-6-methoxyquinolinium 2,4-dinitrophenolate (8A6MQDNP) was synthesized and characterized using FT-IR, FT-Raman, and UV–Vis spectroscopic techniques. The optimized molecular structure, structural properties, and harmonic vibrational frequencies of the molecule were calculated using the DFT/B3LYP method with a cc-pVTZ basis set using the Gaussian 09 software. The observed and calculated vibrational wavenumbers were assigned and correlated well each other. The UV–Vis spectral analysis reveals the π to π* and n to π* electronic transitions of the molecule. The title molecule’s bioactivity is confirmed by frontier molecular orbital (FMOs) analysis; also the intramolecular charge transfer occurred from the quinoline ring to the dinitrophenol. Molecular electrostatic potential surface analysis verifies the FMOs results. The bioactivity of the molecule was confirmed by the natural bond orbital analysis. The Mulliken atomic charge distribution indicates the molecule’s chemical reactivity. Furthermore, the antibacterial results show that the 8A6MQDNP compound can inhibit the development of the tested bacterial strains, most notably the staphylococcus aureus bacterial strain. In vitro cytotoxicity test demonstrates that the 8A6MQDNP compound suppresses the development of A549 cancer cell lines more than HeLa cancer cell lines. Molecular docking investigation confirms that the title molecule inhibits the function of the epidermal growth factor receptor, which has been associated with lung cancer. As a result, the current study paves the way for the development of novel drugs for the treatment of lung cancer.

Abstract 1428: Luminescent immunoassays for homogeneous determination of cell proliferation and senescence

Abstract We have developed homogeneous, luminescent immunoassays for simple and rapid determination of Ki-67 and uPAR levels in 96-well format, thereby enabling efficient and quantitative assessment of proliferation and senescence in mammalian cell culture. Assessment of proliferative capacity is of key importance in numerous research areas, including cancer and various proliferative disorders, assessment of cell fitness (e.g., T cell fitness, stem cell characterization), and evaluation of test compound or drug effects. Cell senescence, characterized in part by loss of proliferative capacity, is an altered, proinflammatory state of cells induced in response to developmental ques, aging, disease, or acute stressors typically involving DNA damage. Ki-67 is a nuclear protein widely used as a marker of proliferation due to its pervasive expression in cycling cells but absence from non-dividing (G0) cells, whether quiescent, senescent, or terminally differentiated. In contrast, urokinase plasminogen activator receptor (uPAR) is a cell-surface protein whose expression was recently reported to increase significantly with the induction of senescence. Of note, commonly used assays of Ki-67 and uPAR levels typically rely upon non-homogeneous methods, including imaging, flow cytometry, or western blotting. Application of Lumit™ technology enabled our development of no-transfer, no-wash immunoassays for Ki-67 (lytic) and uPAR (nonlytic) determinations directly in cell wells. Treatment of human CD8+ T cells with CD3/CD28 T cell activator produced more than a 10-fold upregulation of Ki-67 levels, consistent with induction of T cell proliferation. In contrast, treatment of HCT116 colorectal cancer cells for 48 h with the antiproliferative compounds doxorubicin (100 nM) and nutlin-3A (10 μM) produced 65% and 90% reductions, respectively, in Ki-67 levels normalized to a measure of viable cell number, consistent with their relative antiproliferative activities. Dose-dependent treatment of HCT116 cells with nutlin-3A for 24 and 48 h produced 69% and 93% reduction, respectively, in normalized Ki-67 levels with a potency of ~2.5 μM. Treatment of HCT116 and A549 cancer cell lines for 72 h with 10-20 μM nutlin-3A, in addition to causing profound reduction in Ki-67 levels and loss of proliferative capacity, produced 2.3- to 4-fold increases in cell-surface uPAR levels, reflective of the emergence of the senescence phenotype. These luminescent, homogeneous Ki-67 and uPAR immunoassays provide an efficient means to quantitatively assess changes in cell proliferation and senescence in cell culture models for basic research and drug discovery applications. Citation Format: Dan F. Lazar, Kevin R. Kupcho, Andrew L. Niles, James J. Cali. Luminescent immunoassays for homogeneous determination of cell proliferation and senescence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1428.

Synthesis, crystal structure, computational investigation, molecular docking analysis and anti-lung cancer activity of novel (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one

Ever since the disease of cancer was discovered, man has been mystified by both its mysterious origin and the even more mystifying mechanisms by which it spreads. Although advances in surgery and radiotherapy have significantly impacted cancer treatment, the idea of systemic chemotherapy which is targeted specifically at cancer cells and has minimal side effects remains a strategic goal for the future. A novel thiazolidin-4-one analogue was synthesized by the reaction of 1,2,4,5-tetraazaspiro[5.5]undecane-3-thione with chloroacetic acid. The newly synthesized compound was investigated theoretically as well as experimentally by FT-IR, 1H, 13C NMR and UV–Vis spectra and biologically screened in vitro for its anti-lung cancer activity against A549 cancer cell line. The crystal structure of (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one has been determined by single crystal X-ray diffraction and revealed that it belongs to monoclinic system with cell dimensions: a = 18.9393 (16) Å, b = 5.2747 (4) Å, c = 10.9518 (9) Å, α = 90°, β = 90.214 (3), γ = 90° and V = 1082.85 (15) Å3. Hirshfeld surface analysis was performed to study the nature of intermolecular interactions within the crystal structure via 3D and 2D fingerprint surfaces and to demonstrate H-bonding with close contacts in crystal via dnorm surface. A descriptive study of (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one was done by using density functional theory at DFT/B3LYP/6–311 ++G (d,p) basis set. Results of NLO analysis, ELF, LOL, NCI, AIM, HOMO-LUMO, first hyperpolarizability and molecular electrostatic potential were reported. Theoretical calculation of ADMET properties suggested that the synthesized compounds have a good pharmacokinetic profile. The results of cytotoxic evaluation indicated that (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one has broad-spectrum cytotoxic activity with IC50 values of 240 μM against Human lung carcinoma cell line (A549).

Platinum(IV)-Loaded Degraded Glycol Chitosan as Efficient Platinum(IV) Drug Delivery Platform.

A new class of anticancer prodrugs was designed by combining the cytotoxicity of platinum(IV) complexes and the drug carrier properties of glycol chitosan polymers: Unsymmetrically carboxylated platinum(IV) analogues of cisplatin, carboplatin and oxaliplatin, namely (OC-6-44)-acetatodiammine(3-carboxypropanoato)dichloridoplatinum(IV), (OC-6-44)-acetaodiammine(3-carboxypropanoato)(cyclobutane-1,1-dicarboxylato)platinum(IV) and (OC-6-44)-acetato(3-carboxypropanoato)(1R,2R-cyclohexane-1,2-diamine)oxalatoplatinum(IV) were synthesised and conjugated via amide bonding to degraded glycol chitosan (dGC) polymers with different chain lengths (5, 10, 18 kDa). The 15 conjugates were investigated with 1H and 195Pt NMR spectroscopy, and average amounts of platinum(IV) units per dGC polymer molecule with ICP-MS, revealing a range of 1.3-22.8 platinum(IV) units per dGC molecule. Cytotoxicity was tested with MTT assays in the cancer cell lines A549, CH1/PA-1, SW480 (human) and 4T1 (murine). IC50 values in the low micromolar to nanomolar range were obtained, and higher antiproliferative activity (up to 72 times) was detected with dGC-platinum(IV) conjugates in comparison to platinum(IV) counterparts. The highest cytotoxicity (IC50 of 0.036 ± 0.005 µM) was determined in CH1/PA-1 ovarian teratocarcinoma cells with a cisplatin(IV)-dGC conjugate, which is hence 33 times more potent than the corresponding platinum(IV) complex and twice more potent than cisplatin. Biodistribution studies of an oxaliplatin(IV)-dGC conjugate in non-tumour-bearing Balb/C mice showed an increased accumulation in the lung compared to the unloaded oxaliplatin(IV) analogue, arguing for further activity studies.

Structural and Biological Properties of Heteroligand Copper Complexes with Diethylnicotinamide and Various Fenamates: Preparation, Structure, Spectral Properties and Hirshfeld Surface Analysis

Herein, we discuss the synthesis, structural and spectroscopic characterization, and biological activity of five heteroligand copper(II) complexes with diethylnicotinamide and various fenamates, as follows: flufenamate (fluf), niflumate (nifl), tolfenamate (tolf), clonixinate (clon), mefenamate (mef) and N, N-diethylnicotinamide (dena). The complexes of composition: [Cu(fluf)2(dena)2(H2O)2] (1), [Cu(nifl)2(dena)2] (2), [Cu(tolf)2(dena)2(H2O)2] (3), [Cu(clon)2(dena)2] (4) and [Cu(mef)2(dena)2(H2O)2] (5), were synthesized, structurally (single-crystal X-ray diffraction) and spectroscopically characterized (IR, EA, UV-Vis and EPR). The studied complexes are monomeric, forming a distorted tetragonal bipyramidal stereochemistry around the central copper ion. The crystal structures of all five complexes were determined and refined with an aspheric model using the Hirshfeld atom refinement method. Hirshfeld surface analysis and fingerprint plots were used to investigate the intermolecular interactions in the crystalline state. The redox properties of the complexes were studied and evaluated via cyclic voltammetry. The complexes exhibited good superoxide scavenging activity as determined by an NBT assay along with a copper-based redox-cycling mechanism, resulting in the formation of ROS, which, in turn, predisposed the studied complexes for their anticancer activity. The ability of complexes 1–4 to interact with calf thymus DNA was investigated using absorption titrations, viscosity measurements and an ethidium-bromide-displacement-fluorescence-based method, suggesting mainly the intercalative binding of the complexes to DNA. The affinity of complexes 1–4 for bovine serum albumin was determined via fluorescence emission spectroscopy and was quantitatively characterized with the corresponding binding constants. The cytotoxic properties of complexes 1–4 were studied using the cancer cell lines A549, MCF-7 and U-118MG, as well as healthy MRC-5 cells. Complex 4 exhibited moderate anticancer activity on the MCF-7 cancer cells with IC50 = 57 μM.

The flavonoid hesperidin methyl chalcone as a potential therapeutic agent for cancer therapy: Molecular docking, in vitro cytotoxicity, and in vivo antitumor activity

Hesperidin methyl chalcone (HMC) is a methylation product of the flavanone hesperidin, a flavonoid derived from citrus fruits. Many reports have emphasized the analgesic, anti-inflammatory and antioxidant properties of HMC. However, the anticancer potential of HMC has not been fully elucidated. The objective of this study was to assess the possible anticancer potential of HMC. MTT assay was carried out to assess the in vitro cytotoxicity of HMC against using A549 cancer cell line. In addition, the in vivo antitumor activity of HMC was screened against murine Ehrlich ascites carcinoma (EAC) model, in terms of tumor volume, tumor weight, life span, hematological and biochemical parameters, and compared with that of the anticancer agent, hesperetin. HMC was efficient to suppress the cell viability of A549 cancer cells with an IC50 value of 51.12 µM, which was comparable to that of the anticancer agent hesperetin (IC50 = 49.12 µM). Similarly, in Ehrlich ascites carcinoma model, HMC significantly inhibited the growth of Ehrlich ascites carcinoma with mutual increase in the life span of HMC-treated mice, compared to EAC control. Most importantly, HMC showed a good safety profile as evidenced by restoring hematological profile count of RBCs, WBCs, and hemoglobin to the normal levels. HMC also efficiently reduced the oxidative stress in EAC-bearing mice via increasing the levels of GSH, SOD and Catalase. Collectively, HMC exerted a potent anticancer activity and data presented in this work suggest the usefulness of HMC as a promising candidate in cancer therapy.

Preparation and Characterization of Rutin-Encapsulated Polymeric Micelles and Studies of Synergism with Bioactive Benzoic Acids and Triazolofluoroquinolones as Anticancer Nanomedicines.

The study aimed to examine rutin micelles of advanced superlative dual cytotoxicity-antiinflammtion bioefficacies in substantially novel submicro-nanoaffinities vs. both the raw rutin and reference proapoptotic cisplatin. Antiproliferative capabilities of rutin, benzoic acid (BA) and triazolofluoroqunolone (TFQ) derivatives were reported; hence chemosensitizing effects of rutin or its polymeric micelles (of improved solubility and bioavailability via direct dissolution using the amphiphilic copolymer Pluronic P123) in co-incubations with 5 BAs or 3 TFQ derivatives in a panel of 6 cancer cell lines were verified. Rutin loading in micelles was achieved with a loading efficiency of 59.5 ± 2.9%. The particle size of the micelles was found to be 18 ± 2 nm. Though Rutin loaded nanomicelles were of minimal DPPH radical scavenging activity; they had nitrogen oxide (NO) radical scavenging activity in lipopolysaccharide-induced RAW264.7 macrophages with equipotency to indomethacin (IC50 values (µM) 73.03 vs. 60.88; p=0.057). Remarkably nano-micelle formulation of rutin was proved of significantly more potent antineoplastic bioactivity with submicro-nanomolar affinities in the 6 cancer cell lines vs. both free rutin's and cisplatin's (except A549 lung cancer cell line). Rrutin nanomicelles chemo-sensitized all selected 8 cotreatments with BA derivatives and TFQs and, thus reducing the dose used against breast cancer MCF7 cells to submicro-nanomolar affinities of greater potencies than cisplatin's. Except for Triazolo-4-anisidine cipro butyl acid in PANC1, 2-Amino-3,5-Di iodo BA in A375 and 4-Nitrophenol in A549 incubations; rutin loaded nanomicelles chemosensitized 7/8 cotreating selected benzoic acid (BAs) derivatives and TFQs and chemosensitized pancreatic PANC1, skin A375 and lung A549 cancer cell lines, thus reducing the dose to submicro-nanomolar affinities of greater potencies than cisplatin's. Rutin loaded nanomicelles chemosensitize 6/8 cotreating selected benzoic acid (BA) derivatives and TFQs (except for 2-Amino-5-Bromo Benzoic Acid and Triazolo-4-anisidine cipro butyl acid), thus reducing the dose used against resistant CACO2 colorectal cancer cells.

7,8-Diacetoxy-3-(4-methylsulfonylphenyl)-4-phenylcoumarin Induces ROS-dependent Cell Death in the A549 Human Lung Cancer Cell Line.

Coumarins comprise of a very large class of naturally occurring compounds with growing interest in their synthesis and possible applications in the treatment of various diseases. We herein report the in-vitro cytotoxic activity of 3,4-Diarylcoumarins (4a-i) in A549 (lung) and PC-3 (prostate) cancer cell lines. The cytotoxic activity was evaluated using crystal violet dye-binding. The most active compound effect on the cell-cycle phases, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production and apoptosis were also evaluated. Among the synthesized compounds that were evaluated, 7,8-Diacetoxy-3-(4-(methylsulfonyl)phenyl)-4-phenylcoumrin (4f) showed highest cytotoxicity (CC50=13.5%±0.15μM) in A549 cancer cell line. The mechanism of its cytotoxic action indicated significant cell arrest in G1/G0, S and G2 phases of the cell cycle, loss of mitochondrial membrane potential (MMP), increase in reactive oxygen species (ROS) production and induction of apoptotic cell death. The cell viability result of pretreated A549 cells with antioxidant N-acetylcysteine (NAC), followed by compound 4f treatment confirmed ROS-dependent cell death. The presence of 3-4-methylsulfonyl and 7,8-diacetoxy groups on 3,4-Diarylcoumarin is critical in modulating higher cytotoxic activity and could serve as a valuable template for the development of novel synthetic compounds as potential anticancer agents for lung cancer treatment.

Cytotoxic Effect of Prunus Divaricata Ledeb. Extract on Lung Cancer Cells and Determination of Expression Profiles of Genes in the MAP-Kinase Pathway

Cherry plum (Prunus divaricata Ledeb.) is a diploid fruit tree that belongs to the Rosaceae family. Anticarcinogenic activity of Prunus divaricata Ledeb. methanol extract was examined in lung cancer cell lines A549 and H1299 as well as in healthy cell line Beas-2b in this study. The changes in the expression levels of the most frequently mutated oncogenes in lung cancer, KRAS, EGFR, BRAF, and PIK3CA were investigated as well. In vitro cytotoxicity assays of P. divaricata Ledeb. fruit methanol extract was conducted by measuring the percentage of viable cells spectrophotometrically using the cell viability identification kit (CVDK) based on the colorimetric method. The AB 7500 Fast RT-PCR device with Sybr Green Master Mix was used to create gene expression profiles, and the Ct values of all genes were assessed by normalizing the Ct value of the housekeeping gene. The methanol extract of P. divaricata Ledeb. fruit was found to have a cytotoxic effect on A549 and H1299 cancer cell lines at 20 mg/ml, but not on the Beas-2b cell line at these concentrations. By reducing proliferation, low KRAS and PIK3CA gene expression caused the cells to undergo apoptosis. The methanol extract of P. divaricata Ledeb. fruit has been found to inhibit the development of cancerous cells while promoting the proliferation of healthy cells. We believe it does this through the apoptotic pathway by regulating gene expression levels in oncogenes via the MAP-Kinase pathway.

Aculeaxanthones A-E, new xanthones from the marine-derived fungus Aspergillus aculeatinus WHUF0198.

Dimeric natural products are widespread in plants and microorganisms, which usually have complex structures and exhibit greater bioactivities than their corresponding monomers. In this study, we report five new dimeric tetrahydroxanthones, aculeaxanthones A-E (4-8), along with the homodimeric tetrahydroxanthone secalonic acid D (1), chrysoxanthones B and C (2 and 3), and 4-4'-secalonic acid D (9), from different fermentation batches of the title fungus. A part of the culture was added to a total of 60 flasks containing 300 ml each of number II fungus liquid medium and culture 4 weeks in a static state at 28˚C. The liquid phase (18 L) and mycelia was separated from the fungal culture by filtering. A crude extract was obtained from the mycelia by ultrasound using acetone. To obtain a dry extract (18 g), the liquid phase combined with the crude extract were further extracted by EtOAc and concentrated in vacuo. The MIC of anaerobic bacteria was examined by a broth microdilution assay. To obtain MICs for aerobic bacteria, the agar dilution streak method recommended in Clinical and Laboratory Standards Institute document (CLSI) M07-A10 was used. Compounds 1-9 was tested against the Bel-7402, A-549 and HCT-116 cell lines according to MTT assay. The structures of these compounds were elucidated on the base of 1D and 2D NMR and HR-ESIMS data, and the absolute configurations of the new xanthones 4-8 were determined by conformational analysis and time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations. Compounds 1-9 were tested for cytotoxicity against the Bel-7402, A549, and HCT-116 cancer cell lines. Of the dimeric tetrahydroxanthone derivatives, only compound 6 provided cytotoxicity effect against Bel-7402 cell line (IC50, 1.96 µM). Additionally, antimicrobial activity was evaluated for all dimeric tetrahydroxanthones, including four Gram-positive bacteria including Enterococcus faecium ATCC 19434, Bacillus subtilis 168, Staphylococcus aureus ATCC 25923 and MRSA USA300; four Gram-negative bacteria, including Helicobacter pylori 129, G27, as well as 26,695, and multi drug-resistant strain H. pylori 159, and one Mycobacterium M. smegmatis ATCC 607. However, only compound 1 performed activities against H. pylori G27, H. pylori 26695, H. pylori 129, H. pylori 159, S. aureus USA300, and B. subtilis 168 with MIC values of 4.0, 4.0, 2.0, 2.0, 2.0 and 1.0 μg/mL, respectively.

Phytogenic fabrication of iron oxide nanoparticles and evaluation of their in vitro antibacterial and cytotoxic activity

Several metal-based nanoparticles (NPs) have been found to be toxic and are known to exert adverse health outcomes with irreversible side effects. This highlights the need to discover effective,stable, and biocompatibletherapeutic components using natural sources.Here, a hexane extract ofNigella sativa seeds was used to synthesize iron oxide NPs (NS-IONPs) embedded with N. sativa phytoconstituents.The extract acted as a reducing agent that restricted the size of the NS-IONPs to 5–6 nm, signifying the potential to be cleared through the renal system.The fabricated NS-IONPs had a prominent effect on pathogenic gram-negative bacteria, E. coli (19.3 mm) and Salmonella typhi (14.2 mm) and lung cancer cells (lowest IC50of 18.75 µg/mL) mainly by binding to the phospholipid components of the cell membrane. This resulted in cell shrinkage and further inhibited cell growth. Transmission electron microscopy analyses revealed that themechanisms of cellular NP uptake varied depending on the celltype. Accumulation of NS-IONPs inside the cell increased BAX expression and arrested the cells at the G0/G1 phase, thereby conspicuously extending the G0 phase to initiate necrosis. Thus, these finding suggest that the synthesized NS-IONPs exhibited high antibacterial activity and effective cytotoxicity against cancer cell lines A549 and HCT116 compared to IONPs. The innovation of the current study is that the biogenic fabrication of IONPs is simple and cost effective results in stable nanomaterial, NS-IONPs with potential antibacterial and anticancer activity, which can be explored furthermore for various biomedical applications.

Low-dimensional compounds containing bioactive ligands. Part XXI: Crystal structures, cytotoxic, antimicrobial activities and BSA binding of zinc complexes with 5-chloro-7-nitro-8-hydroxyquinoline

Four new zinc(II) complexes containing molecules of 5-chloro-7-nitro-8-hydroxyquinoline (HClNQ), NH2(CH3)2[Zn(ClNQ)3]·DMF (1), K[Zn(ClNQ)3]·2DMF (2), {Na[Zn(ClNQ)(SO4)(H2O)]}n (3) and [Zn(ClNQ)2(H2O)2] (4), were prepared and characterized by IR and NMR spectroscopy, elemental analysis and single crystal X-ray analysis. Ionic complexes 1 and 2 have similar structures, in which Zn(II) atoms are coordinated by three chelate molecules of ClNQ via oxygen and nitrogen donor atoms forming rare fac isomers. The negative charge of the complex anions is balanced by uncoordinated NH2(CH3)2+ (1) and K+ cations (2). Complex 3 has a polymeric structure in which Zn(II) atom is penta-coordinated by one chelate molecule of ClNQ, one molecule of water and a pair of crystallographically equivalent sulfato ligands, which interconnect adjacent zinc atoms to form a zig-zag chain. The negative charge of the chain is balanced by sodium cations. In a molecular complex 4, equatorial plane is occupied by two chelate ClNQ molecules with nitrogen and oxygen atoms of the two ligands in an infrequent cis-arrangement and axial positions of a distorted octahedron occupy two aqua ligands. HClNQ and complexes 1, 3 and 4 were tested for their antiproliferative activity against HeLa, A549, MCF-7, MDA-MB-231, HCT-116 and Caco-2 cancer cell lines and their selectivity was verified using Cos-7 non-cancerous cell line. The results showed that the complexes exhibited poor nonselective antiproliferative activity. Antibacterial activity of HClNQ and complexes 1, 3 and 4 were tested, too. RIZD (relative inhibition zone diameter) and MIC (minimal inhibitory concentration) showed that complexes 1, 4 and HClNQ inhibited gram-positive bacteria S. aureus. Against gram-negative bacteria E. coli, only HClNQ and 1 were effective in tested concentration. Finally, BSA binding activity of complexes 1 – 4 was investigated by fluorescence quenching measurements.

Ent-Pimarane Diterpenes from the Aerial Parts of Siegesbeckia pubescens.

Five new ent-pimarane diterpenes (1-5) and five known analogs (6-10) were isolated from the aerial parts of Siegesbeckia pubescens. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially 1D and 2D NMR and quantum chemical electronic circular dichroism calculations. All the isolated compounds were evaluated for their cytotoxicity against human BT549, A549 and H157 cancer cell lines. Among them, compounds 1 and 2 showed mild cytotoxicity against lung cancer cell lines H157 with IC50 values of 16.35±2.59 and 18.86±4.83 μM, respectively.

Guided Isolation of An Uncommon Cembranoid Orthoester, Sarcotortin A, and Three Skeletal Diverse Terpenoids from the Hainan Soft Coral Sarcophyton tortuosum Based on Molecular Networking Strategy.

Applying the emerging molecular networking strategy, an uncommon cembranoid orthoester, sarcotortin A (1), featuring a 3/14/8/5-fused scaffold, an unusual eunicellane-type diterpenoid, sarcotorolide A (2), and two new biscembranoids, ximaolides M and N (7 and 8), along with nine known terpenoids 3-6 and 9-13 were isolated from the Hainan soft coral Sarcophyton tortuosum. The structure and absolute configuration of all new compounds were established by a combination of spectroscopic data, X-ray diffraction analysis, and/or quantum chemical computational approaches. The plausible biogenetic relationship among these skeletally different terpenoids was proposed and discussed. In in vitro bioassay, new compound 7 exhibited a remarkable inhibitory activity against protein tyrosine phosphatases 1B (PTP1B) with the IC50 value of 8.06 μM. In addition, compounds 4 and 10 displayed significant inhibitory effects on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophages cells with the IC50 values of 19.13 and 16.45 μM, respectively. Compound 9 showed interesting cytotoxicity against H1975, MDA-MB231, A549, and H1299 cancer cell lines with IC50 values of 31.59, 34.96, 43.87, and 27.93 μM, respectively.

ANTICANCER PROPERTY OF AN AYURVEDIC POLYHERBAL PREPARATION CHIEFLY CONTAINING ARECA NUT AND BETEL LEAF

Background: Areca nut, the nut of the areca palm (Areca catechu L.) and the leaf of betel vine (Piper betle L.) are the two inevitable ingredients of the common chewing mixture popularly known as betel quid. Both traditional and modern research findings proved that these two plant products have many medicinal values, including anticancer properties. With this information, we formulated a polyherbal preparation chiefly containing these two plant products and evaluated its anticancer efficacy on the specific cancer cell line. Methods: The polyherbal preparation called ‘Pugasaram’ was prepared using 12 different plant products, including areca nut and betel leaf, in different proportions. It was screened for its anticancer properties against A549 cancer cell lines. Results: The study showed a dose-dependent cytotoxicity of ‘Pugasaram’ on cultured A549 cancer cells with the IC50 value of 109.32 µg/ml. Conclusion: The present study reveals great potential for ‘Pugasaram’ to develop as an effective anticancer drug. This information could be the basis for further studies in this field.

GC/MS Analysis, Cytotoxicity, and Antiviral Activities of Annona glabra Hexane Extract Supported by In Silico Study.

Annona glabra Linn is employed in conventional medicine to treat a number of human disorders, including cancer and viruses. In the present investigation, the significant phytochemical components of Annona glabra hexane extract were identified using gas chromatography-mass spectrometry (GC-MS) analysis. Three major compounds were identified in the hexane extract: tritriacontane (30.23%), 13, 17-dimethyl-tritriacontane (22.44%), and limonene (18.97%). MTT assay was used to assess the cytotoxicity of the extract on six human cancer cell lines including liver (HepG-2), pancreas (PANC-1), lung (A-549), breast (MCF-7, HTB-22), prostate (PC-3), and colon (CACO-2, ATB-37). The extract exhibited significant cytotoxic activity against both CACO-2 and A-549 cancer cell lines (IC50 = 47 ± 0.74 μg/mL and 56.82 ± 0.92 μg/mL) in comparison with doxorubicin (IC50 = 31.91 ± 0.81 μg/mL and 23.39 ± 0.43 μg/mL) and of SI of 3.8 and 3.1, respectively. It also induced moderate-to-weak activities against the other cancerous cell lines: PC-3, PANC-1, MCF-7, and HepG-2 (IC50 = 81.86 ± 3.26, 57.34 ± 0.77, 80.31 ± 4.13, and 57.01 ± 0.85 μg/mL) in comparison to doxorubicin (IC50 = 32.9 ± 1.74, 19.07 ± 0.2, 15.48 ± 0.84 and 5.4 ± 0.22 μg/mL, respectively) and SI of 2.2, 3.1, 2.2, and 3.1, respectively. In vitro anti-HSV1 (Herpes simplex 1 virus) and HAV (Hepatitis A virus) activity was evaluated using MTT colorimetric assay with three different protocols to test protective, anti-replicative, and anti-infective antiviral activities, and three separate replications of each experiment were conducted. The plant extract showed promising protective and virucidal activity against HSV1 with no significant difference with acyclovir (79.55 ± 1.67 vs. 68.44 ± 7.62 and 70.91 ± 7.02 vs. 83.76 ± 5.67), while it showed mild protective antiviral activity against HAV (48.08 ±3.46) with no significant difference vs. acyclovir (36.89 ± 6.61). The selected main compounds were examined for their bioactivity through in silico molecular docking, which exhibited that limonene could possess the strongest antiviral properties. These findings support Annona glabra's conventional use, which is an effective source of antiviral and anticancer substances that could be used in pharmaceuticals.