Moderate Cytotoxic Effect Research Articles

Cytotoxicity Effect and Morphological Changes of Chrysanthemum Morifolium Methanolic Extract against Chronic Myeloid Leukaemia K-562 Cell Line

Chrysanthemum morifolium, also known as “Bunga kekwa” in Malaysia, has various benefits and widely used in Chinese herbal medicines. The plant extract was reported to have significant biological activities, such as anti-inflammation, anti-tumour, anti-oxidant, and anti-cancer. Nonetheless, its anti-cancer potential on chronic myeloid leukaemia has remained elusive. The main goal of this study is to evaluate the cytotoxic effect of C.morifolium buds and flowers in methanolic extracts on chronic myeloid leukaemia malignancy K-562 cell lines. The bud and flower of C.morifolium were macerated for 72 hours in 100% methanol then were concentrated under reduced pressure using a rotary evaporator and oven-dried to obtain crude extracts. K-562 cells were treated with six different concentrations 400, 200, 100, 50, 25, and 12.5 µg/ml and incubated for 24, 48 and 72 hours. The in vitro cytotoxic activity was measured using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) test and was quantified using a microplate reader at 570 nm. Acridine orange and propidium iodide (AO/PI) staining were used to assess morphological alterations. MTT assays results showed moderate toxicity of both extracts. The lowest maximal half inhibitory concentration (IC50) value were observed at 72 hours of incubation; 182 ± 4.04 ug/ml for BM and 161 ± 7.88 ug/ml for flower extract (FM). However, there was a significantly different IC50 value (p<0.05) between the incubation periods of both treatments where the IC50 value at 24 hours was 301.33 ± 8.51 ug/ml 301 µg/ml in BM, 216 ± 10.79 ug/ml 216 µg/ml in FM and at 48 hours was 227 ± 12.25 ug/ml 227 µg/ml in bud extract (BM), 174 ± 11.92 ug/ml 174 µg/ml in FM. The morphological changes evidence was shown in AO/PI staining by the appearance of a mixed population of cells; early apoptosis, late apoptosis and necrotic cells. These findings suggested that methanolic C.morifolium extracts showed moderate cytotoxic effect on chronic myeloid leukaemia K-562 cells. Further study needed to identify the mode and mechanism of cell death in K-562 cells treated with the C.morifolium extracts.

Cytotoxic Effect of Red Sandal Mediated Silver Nanoparticles Mouthwash Using Brine Shrimp Lethality Assay: An In-vitro Study

Background: Silver Nanoparticles (AgNP) plays a crucial role in nanoscience, nanotechnology and nanomedicine. AgNP has antibacterial, antifungal, antiviral, anti-inflammatory, anti-antigenic, anticancer and cytotoxic properties. Cytotoxic effects of mouthwashes on the gingival tissue have always been a priority. Pterocarpus santalinus, with the common name of red sandalwood. The aim of the study is to evaluate the cytotoxic effect of red sandal mediated silver nanoparticles mouthwash using brine shrimp lethality assay.
 Materials and Methods: The mouthwash was prepared using red sandal mediated silver nanoparticles, ethanol, distilled water, sucrose, sodium benzoate, clove oil, sodium dodecyl phosphate with 0.1% in concentration. The methodology includes green synthesis of Red sanders mediated Silver Nanoparticles synthesis followed by tests for Cytotoxic effect using mouthwash.
 Results: Red sanders mediated silver nanoparticles have high potent cytotoxic potential, it has been proved with the help of brine shrimps. LD50 concentration was obtained to be 80µL, with half the population of nauplii in the respective well surviving post incubation. 
 Conclusion: From the observed result, it has been concluded that Pterocarpus santalinus/red sandal mediated silver nanoparticles mouthwash has a considerably moderate cytotoxic effect. It is a rich source of various potential phytochemicals and is a simple, rapid, stable and cost effective method for nano based medical applications.

Cytotoxic effects of the biflavonoids isolated from Selaginella trichoclada on MCF-7 cells and its potential mechanism

A new biflavonoid, (2′'S)-6′'-methyl-2′',3′'-dihydroochnaflavone (1), along with two known ochnaflavones (2, 3), four known amentoflavones (4–7) and two known robustaflavones (8, 9) were obtained from the 70% EtOH extract of Selaginella trichoclada. The chemical structures of isolated compounds were elucidated by extensive spectroscopic analyses. Overall, compounds 1–9 displayed moderate cytotoxic effects against human breast cancer MCF-7 cell lines. Among them, compounds 2 and 8 exhibited relatively strong cytotoxic effects against MCF-7 cells with an IC50 value of 7.7 and 6.9 μΜ, respectively. The results of RNA-sequencing and KEGG functional enrichment analysis showed that 8 could induce ferroptosis in MCF-7 cells by down-regulating the expression of ferroptosis-related genes including ACSL4, NOXO1, NOXA1, ACSL5, STEAP3, LPCAT3, ATG7 and TP53. Then 8 could inhibit the expression of ACSL4 proteins through molecule docking analysis, which showed a strong interaction of − 11.89 Kcal/mol binding energy. Those results indicate that 8 could be chemotherapy agents to fight drug resistance in breast cancer by down-regulating the expression level of ACSL4 proteins via ferroptosis, which needs to be further certified in vitro.

Two new steroidal alkaloids with cytotoxic activities from the roots of Veratrum grandiflorum Loes.

• Two new steroidal alkaloids were obtained from roots of Veratrum grandiflorum Loes. • Their structures were elucidated on the basis of extensive spectroscopic techniques. • Compounds 3 , 4 exhibited moderate cytotoxic effects against four cancer cell lines. Two new steroidal alkaloids, Grandivine A and B ( 1 and 3 ), together with eight known related compounds were obtained from the roots of Veratrum grandiflorum Loes. The structures of the compounds were elucidated though extensive spectroscopic techniques. Compounds 3 and 4 exhibited moderate cytotoxic effects against four cancer cell lines.

GC/MS Analysis of Essential Oil and Enzyme Inhibitory Activities of Syzygium cumini (Pamposia) Grown in Egypt: Chemical Characterization and Molecular Docking Studies.

Syzygium cumini (Pomposia) is a well-known aromatic plant belonging to the family Myrtaceae, and has been reported for its various traditional and pharmacological potentials, such as its antioxidant, antimicrobial, anti-inflammatory, and antidiarrheal properties. The chemical composition of the leaf essential oil via gas chromatography–mass spectrometry (GC/MS) analysis revealed the identification of fifty-three compounds representing about 91.22% of the total oil. The identified oil was predominated by α-pinene (21.09%), followed by β-(E)-ocimene (11.80%), D-limonene (8.08%), β-pinene (7.33%), and α-terpineol (5.38%). The tested oil revealed a moderate cytotoxic effect against human liver cancer cells (HepG2) with an IC50 value of 38.15 ± 2.09 µg/mL. In addition, it effectively inhibited acetylcholinesterase with an IC50 value of 32.9 ± 2.1 µg/mL. Furthermore, it showed inhibitory properties against α-amylase and α-glucosidase with IC50 values of 57.80 ± 3.30 and 274.03 ± 12.37 µg/mL, respectively. The molecular docking studies revealed that (E)-β-caryophyllene, one of the major compounds, achieved the best docking scores of −6.75, −5.61, and −7.75 for acetylcholinesterase, α-amylase, and α-glucosidase, respectively. Thus, it is concluded that S. cumini oil should be considered as a food supplement for the elderly to enhance memory performance and for diabetic patients to control blood glucose.

In vitro REGULATION OF THE EXPRESSION OF THE SARS-CoV-2 RECEPTOR ANGIOTENSIN-CONVERTING ENZYME (ACE2) IN LUNG CANCER CELLS BY NATURAL PRODUCTS

The COVID-19 pandemic continues infecting people causing deaths globally. Although various medicines have been tried to combat with COVID-19, there is no medicine or treatment that has been validated yet. People have been using natural products for centuries against bacterial and viral illnesses. This study aimed to test the effects of the biomolecule oleuropein, whey collected from industrial waste and soaproot extracts obtained from Gypsophila arrostii Guss. var. nebulosa Boiss. & Heldr. and Saponaria officinalis L. on the expression of the human ACE2 gene as SARS-CoV-2 receptor on the A549 adenocarcinoma cell-line by Real-Time Quantitative Polymerase Chain Reaction (qPCR). According to the cytotoxicity tests, G. arrostii var. nebulosa and S. officinalis extract treatments showed a dose dependent cytotoxic effect on the cells. The EC50 values of G. arrostii var. nebulosa and S. officinalis were found to be 54.3 μg/ml and 17.3 μg/ml, respectively. Oleuropein showed moderate cytotoxic effects with the EC50 value over 250 μg/ml. Whey (fermented and non-fermented) did not show any cytotoxic effect at the applied doses. The qPCR results showed that the ACE2 mRNA level decreased by 89.8% and 35.2% due to the fermented and non-fermented whey extracts, respectively. Similarly, G. arrostii var. nebulosa and S. officinalis downregulated ACE2 by 79.8% and 90.1%, respectively. In contrast, oleropein upregulated ACE2 (102.8%). Our results showed that the natural supporting products produced from soaproot extracts and fermented whey can be used against COVID-19 by both cancer patients and people in potential risk groups.

Supramolecular architectures in dihydropyridones: Synthesis, crystal structure, Hirshfeld analysis, cytotoxicity and in silico studies

In this study, a series of five non-aromatic dihydropyridones were synthesized, crystallized, and single-crystal X-ray diffraction was used to obtain their molecular geometries. The supramolecular assembly of the molecules through non-covalent interactions was then studied and demonstrated. The weak intermolecular interactions in the molecular packing of compounds were further validated through Hirshfeld surface analysis. The synthesized compounds were screened in vitro using lung adenocarcinoma (A549) cells to assess their cytotoxic effects. A molecular docking study has also been employed to gain insight into the binding mode of the synthesized compounds in the allosteric binding pocket of the Eg5 motor domain and survivin protein. The results showed that the title compounds have mild to moderate cytotoxic effects in these cells. Ethyl-5-cyano-4-(2,5-dimethoxyphenyl)-2-methyl-6-oxo-1,4,5,6-tetrahydropyridine-3-carb-oxylate has shown more significant cytotoxicity among all the synthesized compounds. This study has further demonstrated the importance of non-covalent intermolecular interactions of dihydropyridones for exhibiting diverse supramolecular architectures as well as for having a significant binding affinity towards the receptor.

Euphorfistrines A-G, cytotoxic and AChE inhibiting triterpenoids from the roots of Euphorbia fischeriana

Seven new triterpenoids including two cycloartanes (1–2), a lanostane (3), a tirucallane (4), a dammarane (5), an ursane (6), and an oleanane (7), along with nineteen known triterpenoids (8–26), have been obtained from the roots of Euphorbia fischeriana. Their structures were established by NMR, HRESIMS, single-crystal X-ray diffraction analysis, Mosher's method, NMR calculations, ECD analysis, and comparison with structurally related known analogues. Among them, compounds 1 and 8 were a pair of cycloartane-type triterpenoids epimers. Our bioassays have established that compounds 1–5 and 10 displayed moderate cytotoxic effects, and the structure–activity relationships of cycloartane-type triterpenoids (CTTs) were further examined. Notably, some triterpenoids displayed moderate inhibitory effects against AChE by an in vitro screened experiment. Triterpenoid 7 (Euphorfistrine G, ETG) displayed the potent inhibitory effect with IC50 = 2.45 and Ki = 2.30 μM (inhibition kinetic). And, in silico docking analyses have been performed to investigate the inhibitory mechanism of compound 7.

Biosynthesis and evaluation of a novel highly water-soluble quercetin glycoside derivative

Quercetin (1) was converted into quercetin 7-O-succinyl glucoside (2) by used Bacillus amyloliquefaciens FJ18 as a solvent-resistant whole-cell biocatalyst. The structure of the new compound was confirmed by LC-MS analysis and NMR spectroscopy. The water-solubility of this novel quercetin 7-O-succinyl glucoside (2) was approximately 1000 times higher than that of native quercetin (2). Quercetin (1) and quercetin 7-O-succinyl glucoside (2) exhibited significant DPPH scavenging capacity with IC50 values of 23.55 and 36.05 µM, respectively. Both compounds showed moderate cytotoxic effects against the two human cancer cell lines (MCF-7 and HepG2) with IC50 values ranging from 39.45-63.38 µM.

Cytotoxic and anti-inflammatory effects of chitosan and hemostatic gelatin in oral cell culture.

Chitosan is a biopolymer with bactericidal/bacteriostatic effect, biocompatible and biodegradable. It has been used in tissue engineering to replace tissues partially or completely by releasing bioactive materials or influencing cell growth, usually in regenerative medicine and dentistry. The aim of this study was to evaluate the cytotoxic and anti-inflammatory effect of chitosan alone or with hemostatic gelatin (Spongostand®) in cultures of human pulp cells (HPC), human gingival fibroblasts (HGF) and mouse pre-osteoblasts (MC3T3-E1, ATCC). HPC and HGF were isolated from patients. Cells were subcultured in DMEM. Chitosan was inoculated at different concentrations (0-0.5%) and hemostatic gelatins impregnated with chitosan (0.19%) were placed directly in the presence of cells and incubated for 24 hours. Cell viability was determined by MTT method and mean cytotoxic concentration (CC50) was calculated from the dose-response curve. Anti-inflammatory effect was calculated from the in vitro gingivitis model induced with interleukin 1beta (IL-1β) in HGF and protein detection. The data were subjected to Shapiro-Wilk, Kruskal-Wallis and Mann-Whitney tests. Experiments were performed in triplicate of three independent assays. Cell viability of HPC, HGF and MC3T3-E1 in contact with chitosan decreased significantly (p<0.05). The HPC were the most sensitive (CC50= 0.18%), followed by HGF (CC50= 0.18%) and MC3T3-E1 (CC50= 0.19%). The cytotoxicity of gelatins impregnated with chitosan decreased cell viability of HGF and HPC by 11% and 5%, respectively. The proinflammatory effect was reduced significantly in the gingivitis model. To conclude, chitosan induces moderate cytotoxic effects alone or with hemostatic gelatin at 0.19%, in dose-dependent manner, with anti-inflammatory effects on human gingival fibroblasts. The use of chitosan as a biomaterial can be an excellent choice for use in regenerative dentistry.

Stelleranoids A–M, guaiane-type sesquiterpenoids based on [5,7] bicyclic system from Stellera chamaejasme and their cytotoxic activity

Thirteen previously undescribed guaiane-type sesquiterpenoids based on [5,7] bicyclic system, stelleranoids A–M (1–13), along with six known analogues (14–20), were isolated from the roots of Stellera chamaejasme with chromatographic techniques. Their structures including absolute configurations were determined by HRESIMS and spectroscopic data, quantum chemical calculations, as well as X-ray crystallographic analysis. Cytotoxicity test in three cell lines indicated that compound 14 had relatively stronger cytotoxic effect against MKN-45, SKOV3, and Du145 cell lines with IC50 of 9.8, 17.4 and 7.3 μM, respectively; compounds 3 and 8 displayed moderate cytotoxic effect against MKN-45 and Du145 cell lines with IC50 ranged from 14.5 to 18.8 μM, comparable to those of the positive control. As determined by fluorescent microscopy and flow cytometry in Du145 cell line, compound 14 could promote cell apoptosis and cause cell cycle arrest at the G0/G1 phase, leading to the inhibition of cell proliferation. Further Western blot analysis revealed that this inhibitory effect was accompanied by upregulating pro-apoptosis proteins cleaved-PARP, cleaved-Caspase-9 and tumor suppressor protein p53 while downregulating anti-apoptotic protein Bcl-2 in 14-treated Du145 cells.

Bioactivity evaluation for volatiles and water extract of commercialized star anise

BackgroundUsually, it takes about a year since the harvested fresh star anise fruit (SAF) reaches the market for consumer usage, all this time with different handling processes and different storage circumstances greatly affect its quality as well as its chemical composition and biological activity. AimThis study investigated the chemical constituents for volatiles and water extracts of commercialized SAF, as well as, their bioactivities. ResultsThe chemical constituents were dominated by Trans-Anethole (47.16 %), estragole (14.4 %), and foeniculin (8.86 %) in the essential oils. Meanwhile, Coumarin, Apigenin, and Rosmarinic were the predominant phenolics of water extract. The result reflects a distinction of water extract to minimize mycotoxin secretion in liquid media. The SAF-volatiles were more effective in inhibiting microbial growth of the investigated bacterial and fungal strains. ConclusionAlthough samples were commercially collected from markets, their extracts were still capable to inhibit up to 55 % of fungal growth. The SAF water extract exhibited a moderate and selective cytotoxic effect (IC50 = 114.9 μg/ml) against HepG2 cell lines compared to the low impact of essential oil (IC50 = 513.8 μg/ml). Which led to the conclusion that despite the long-time span for SAF till it reaches the market, aqueous extract maintained a good ability for reducing mycotoxins-secretion from fungi grown in liquid media. This result emphasizes the role of the phenolics of water extracts' as an anti-mycotoxigenic agent.

Impact of toxicity effects of zinc oxide nanoparticles in rats within acute and subacute experiments

Introduction. Occupational air is contaminated with zinc oxide nanoparticles in the copper smelting industry, especially in the smelting of brass and copper. A wide range of toxic effects with varied clinical symptomatology is observed in zinc and its compounds. Competitive relations with many other metals, including calcium, copper, and iron, are the foundation of most cases of zinc intoxication. Long-term administration of zinc or its compounds to laboratory rodents affects enzymes, carbohydrates and mineral metabolism. Materials and methods. Subchronic intoxication with repeated intraperitoneal injections and acute low respiratory tract reaction to a single intratracheal injection of zinc nanoparticles were simulated in outbred white rats. Water suspensions of zinc oxide nanoparticles with a 30-80 nm diameter were applied in both experimental models. Upon completion of the exposure, the condition of the rats in all groups was evaluated in many generally accepted criteria for toxicity. The student’s t-test was applied for statistical analysis of the obtained data. Results. Moderate intoxication development in a subchronic experiment is demonstrated. Homogeneous ultrastructural changes in the spleen tissue were revealed. Mitochondrial damage with partial or complete loss of crista is the most common. The fragmentation ratio of DNA was found by a statistically significant increase. A single intratracheal injection of zinc oxide nanoparticles revealed the increase in the attraction of cells capable of their phagocytosis (mainly neutrophils) into the low respiratory tract. This shows their cytotoxicity. Conclusion. Moderate general toxic and cytotoxic effects of zinc oxide nanoparticles on the rat body were identified.

Combinations of indole based alkaloids from Mitragyna speciosa (Kratom) and cisplatin inhibit cell proliferation and migration of nasopharyngeal carcinoma cell lines

Ethnopharmacological relevanceMitragyna speciosa (Korth.) or kratom is a medicinal plant indigenous to Southeast Asia. The leaf of M. speciosa is used as a remedy in pain management including cancer related pain, in a similar way as opioids and cannabis. Despite its well-known analgesic effect, there is a scarce of information on the cancer-suppressing potential of M. speciosa and its active constituents. Aim of the studyTo assess the potential applicability of M. speciosa alkaloids (mitragynine, speciociliatine or paynantheine) as chemosensitizers for cisplatin in Nasopharyngeal carcinoma (NPC) cell lines. Materials and methodsThe cytotoxic effects of the extracts, fractions and compounds were determined by conducting in vitro cytotoxicity assays. Based on the cytotoxic screening, the alkaloid extract of M. speciosa exhibited potent inhibitory effect on the NPC cell line NPC/HK1, and therefore, was chosen for further fractionation and purification. NPC cell lines NPC/HK1 and C666-1 were treated with combinations of cisplatin and M. speciosa alkaloids combinations in 2D monolayer culture. The effect of cisplatin and mitragynine as a combination on cell migration was tested using in vitro wound healing and spheroid invasion assays. ResultsIn our bioassay guided isolation, both methanolic and alkaloid extracts showed mild to moderate cytotoxic effect against the NPC/HK1 cell line. Both NPC cell lines (NPC/HK1 and C666-1) were insensitive to single agent and combination treatments of the M. speciosa alkaloids. However, mitragynine and speciociliatine sensitized the NPC/HK1 and C666-1 cells to cisplatin at ~4- and >5-fold, respectively in 2D monolayer culture. The combination of mitragynine and cisplatin also significantly inhibited cell migration of the NPC cell lines. Similarly, the combination also of mitragynine and cisplatin inhibited growth and invasion of NPC/HK1 spheroids in a dose-dependent manner. In addition, the spheroids did not rapidly develop resistance to the drug combinations at higher concentrations over 10 days. ConclusionOur data indicate that both mitragynine and speciociliatine could be potential chemosensitizers for cisplatin. Further elucidation focusing on the drug mechanistic studies and in vivo studies are necessary to support delineate the therapeutic applicability of M. speciosa alkaloids for NPC treatment.

Idelalisib Interferes with the Crosstalk of Follicular Lymphoma and Its Immune Microenvironment and Potentiates the Activity of ABT-199

Background:The PI3K pathway is crucial in B-cell non-Hodgkin lymphoma (NHL) cell survival by regulation of cell cycle, apoptosis, proliferation, differentiation, homing, and retention. Idelalisib (IDELA/GS-1101/CAL-101) is a first-in-class PI3Kδ selective inhibitor that is approved for the treatment of relapsed chronic lymphocytic leukemia and follicular lymphoma (FL). The mechanisms of IDELA sensitivity and resistance remain to be fully elucidated.We aimed to characterize the cellular and molecular effects of IDELA in an in vitro model utilizing a primary FL cell co-culture system with follicular dendritic cells (FDC) or M2-polarized macrophages (M2), both subpopulations related to poor prognosis, in order to explore possible combinatorial regimens.Methods: FL primary cells from lymph node biopsies were co-cultured (or not) (24-72h) with FDC cells or M2 macrophages. Viability of FL cells was assessed by flow cytometry (AnnexinV/7-AAD). B cells were isolated using CD20 magnetic beads, RNA extracted and subjected to gene expression profiling (GEP), and data analyzed by Gene Set Enrichment Analysis (GSEA).Results: In the absence of accompanying cells, IDELA (100-500nM) induced a moderate cytotoxic effect on FL cells (n=10) that was maintained in FL-FDC and FL-M2 co-cultures. GEP analysis indicated that IDELA (500nM, 48h) induced a downregulation of genes related to germinal center (GC) program, CD40L, and NF-kB pathways, together with other pathways related to B cell-T cell crosstalk. In this sense, IDELA treatment reduced the expression on B-cells of key molecules such as ICOSL (TFH activation) and CCL22 (Treg activation).In the context of FL-FDC co-culture, FDC induced the transcription of genes related to B-cell receptor-, CD40- and NF-kB-signaling pathways, GC program, mechanistic target of rapamycin (mTOR), angiogenesis, extracellular matrix remodeling, and migration, among others. IDELA blocks the activation of the mTOR pathway in all FL samples analyzed (n=4), but displayed differential activity on the rest of the pathways. We are currently investigating the molecular basis of these selective molecular responses to IDELA in vitro and its possible correlation with the presence of somatic mutations in FL (CREBBP, EP300, EPHA7, EZH2, KMT2D, MEF2B, RRAGC, TNFAIP3 and TNFRSF14).We have also explored the combination of IDELA with the B-cell lymphoma 2 (BCL2) inhibitor ABT-199/Venetoclax and have uncovered a synergistic interaction between the two drugs that is maintained in FL-FDC/M2 co-cultures (n=9). This synergy may be linked to the downregulation of the anti-apoptotic proteins Mcl-1, Bcl-XL, and BFL-1 induced by IDELA, together with the induction of the pro-apoptotic BH3-only HRK and BIM. We are currently performing BH3 profiling of FL primary cellswith FDC-M2 co-cultures to identify which patients may be more susceptible to this drug combination.Conclusions: Our results suggest a differential role of IDELA in the context of FL-FDC/FL-T cell crosstalk that may be linked to the mutational patient profile. IDELA ABT-199 combination treatment is highly efficacious in FL-FDC/M2 co-cultures. DisclosuresYahiaoui:Gilead Sciences, Inc.: Employment, Equity Ownership. Lopez-Guillermo:Janssen: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Roche: Consultancy, Other: Research grant; Novartis: Consultancy. Roue:Gilead Sciences, Inc.: Research Funding. Tannheimer:Gilead Sciences, Inc.: Employment. Pérez-Galán:Gilead Sciences, Inc.: Research Funding.

Bioactive indole alkaloids from insect derived endophytic Aspergillus lentulus

As part of our program to discover new bioactive agents from endophytic fungi, three new indole alkaloids (1–2, 4) along with twelve known compounds were isolated from an inset derived endophytic strain Aspergillus lentulus. Their structures were determined by comprehensive spectroscopic analyses of 1D/2D NMR and HR-ESI-MS data. The absolute configurations were confirmed by ECD calculation using Time-dependent Density functional theory (TD-DFT) at the B3LYP/6–31 + g (d, p) level and Rh2(OCOCF3)4-induced ECD experiments. Compounds 2, 4, 5, 13 and 15 exhibited moderate cytotoxic effects on A549 cell line with IC50 in the range of 17.92–48.29 μM. Compounds 1, 2 and 13–15 displayed the anti-bacterial activity against Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola with MIC values ranging from 25 to 100 μg/mL.

1H-benzimidazole-2-yl hydrazones as tubulin-targeting agents: Synthesis, structural characterization, anthelmintic activity and antiproliferative activity against MCF-7 breast carcinoma cells and molecular docking studies

In the present study, fifteen benzimidazolyl-2-hydrazones 7a-7o of fluoro-, hydroxy- and methoxy-substituted benzaldehydes and 1,3-benzodioxole-5-carbaldehyde were synthesized and their structure was identified by IR, NMR, and elemental analysis. The compounds 7j 2-(3-hydroxybenzylidene)-1-(5(6)-methyl-1H-benzimidazol-2-yl)hydrazone and 7i 2-(3-hydroxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazone have exerted the strongest anthelmintic activity (100% after 24 h incubation period at 37 °C) against isolated muscle larvae of Trichinella spiralis in an in vitro experiment. The in vitro cytotoxicity assay towards MCF-7 breast cancer cells and mouse embryo fibroblasts 3T3 showed that the studied benzimidazolyl-2-hydrazones exhibit low to moderate cytotoxic effects. The ability of the studied benzimidazolyl-2-hydrazones to modulate microtubule polymerization was confirmed and suggested that their anthelmintic action is mediated through inhibition of the tubulin polymerization likewise the other known benzimidazole anthelmitics. It was also shown that the four most promising benzimidazolyl-2-hydrazones do not affect significantly the AChE activity even at high tested concentration, thus indicating that they do not have the potential for neurotoxic effects. The binding mode of compounds 7j and 7n in the colchicine-binding site of tubulin were clarified by molecular docking simulations. Taken together, these results demonstrate that for the synthesized benzimidazole derivatives the anthelmintic activity against T. spiralis and the inhibition of tubulin polymerization are closely related.

Chemical Profiling, Pharmacological Insights and In Silico Studies of Methanol Seed Extract of Sterculia foetida.

Sterculia foetida, also known as jangli badam in Bangladesh, is a traditionally used plant that has pharmacological activities. A qualitative phytochemical analysis was performed to assess the metabolites in a methanolic extract of S. foetida seeds (MESF), and the cytotoxic, thrombolytic, anti-arthritics, analgesic, and antipyretic activities were examined using in vitro, in vivo, and in silico experiments. Quantitative studies were performed through gas chromatography-mass spectroscopy (GC-MS) analysis. The brine shrimp lethality bioassays and clot lysis were performed to investigate the cytotoxic and thrombolytic activities, respectively. The anti-arthritics activity was assessed using the albumin denaturation assay. Analgesic activity was determined using the acetic acid-induced writhing test and the formalin-induced paw-licking test. A molecular docking study was performed, and an online tool was used to perform ADME/T (absorption, distribution, metabolism, and excretion/toxicity) and PASS (Prediction of Activity Spectra for Substances). GC-MS analysis identified 29 compounds in MESF, consisting primarily of phenols, terpenoids, esters, and other organic compounds. MESF showed moderate cytotoxic activity against brine shrimp and significant thrombolytic and anti-arthritics activities compared with the relative standards. The extract also showed a dose-dependent and significant analgesic and antipyretic activities. Docking studies showed that 1-azuleneethanol, acetate returned the best scores for the tested enzymes. These findings suggested that MESF represents a potent source of thrombolytic, anti-arthritic, analgesic, antipyretic agents with moderate cytotoxic effects.

Antimicrobial and cytotoxic potential of an endophytic fungus Alternaria tenuissima AUMC14342 isolated from Artemisia judaica L. growing in Saudi Arabia

In this study, 19 endophytic fungal isolates associated with Artemisia judaicaL. were isolatedfrom Al-Shihiyah, Haʾil, Saudi Arabia. Those isolates represented five genera, including: Alternaria sp., (predominantly), Aspergillus sp., Chaetomium sp., Cladosporium sp., and Fusarium sp. All isolates (6 species) were grown on a solid rice medium and their ethyl acetate crude extracts, beside A. judaica L. extract, were tested for their antimicrobial activity. One endophytic fungal isolate demonstrated the highest activity and was chosen for further investigation. Based on its phenotypic, ITS ribosomal gene sequences, and phylogenetic characterization, this isolate was identified as Alternaria tenuissima AUMC14342 with accession number (MT468650). Ethyl acetate (EtOAc) extract from the isolated strain, AUMC14342, was fractioned using VLC. The active fraction of the EtOAc exhibited good antimicrobial effect against P. aeruginosa, S.aureus, F. solani, and A. niger at conc. 30 µ/mL using disc diffusion assay. A moderate cytotoxic effect was reported against a Hepatocellular carcinoma cell line (HepG2), with the lowest inhibitory concentration (IC50) of 0.52 µM. The active fraction was characterized by the presence of different chemically terpene, ester, volatile, and other organic compounds, determined by GC–MS. Conclusively, the endophytic fungus, A. tenuissima, derived from A .judaicaL.,is an ideal candidate for the potential industrial production of antimicrobial agents with a variety of applications.

Structurally diverse polyprenylated acylphloroglucinols from Hypericum uralum Buch.-Ham. ex D. Don

Uralins A − D, four undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) featuring an unprecedented fused hexacyclic architecture, a unique monocyclic tetra-seco-tetranor-b-PPAP, an oxidative b-PPAP and a rare norspiroindane-type m-PPAP, respectively, were isolated from the aerial parts of Hypericum uralum, along with ten known PPAPs. Their structures and absolute configurations were elucidated by extensive spectroscopic techniques (MS, NMR, [α]D, CD), conceivable biogenetic pathways and time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations. Biological assays showed three b-PPAPs had moderate antioxidative damage activities, while spiroindanes exhibited moderate cytotoxic effects.