Considerable Cytotoxic Activity Research Articles

Computational Study and Biological Evaluation of Isolated Saponins from the Fruits of Gleditsia aquatica and Gleditsia caspica

Phytochemical study of the ethanolic extract of the fruits of Gleditsia aquatica and Gleditsia caspica resulted in the isolation of the triterpene saponins; aquaticasaponin A (1), aquaticasaponin B (2), caspicaoside L (3) and caspicaoside M (4). Compound (1) showed good activity against methicillin resistant Staphylococcus aureus (MRSA) (IC50 =16.3 μg/mL) and Staphylococcus aureus (non-MRSA), (IC50 =12.2 μg/mL) and it expressed considerable cytotoxic activity against BT-549 (Human Ductal Carcinoma, Breast), KB (Human Epidermal Carcinoma, Oral) and SK-MEL (Human Malignant Melanoma) with IC50 values of 8.3, 10.0 and 3.3 μg/mL, respectively. Compounds (2) and (3) showed potent cytotoxicity against BT-549 with IC50 values of 5.3 and 7.3 μg/mL, and against SK-MEL with IC50 values of 4.3 and 3.1 μg/mL, respectively. Compound (4) showed good cytotoxicity against KB with IC50 value of 7.3 μg/mL. In consistent, the study of molecular determinates of cytotoxic activity of these new scaffolds showed close high docking scores to CD81 (Cluster of Differentiation 81) human antigen which could be of great importance for the development of new cytotoxic candidates. The structure identification of isolated metabolites was carried out using 1D and 2D NMR and mass spectra.

Study of the venom proteome of Vipera ammodytes ammodytes (Linnaeus, 1758): A qualitative overview, biochemical and biological profiling

Vipera ammodytes (Va), is the European venomous snake of the greatest medical importance. We analyzed whole venom proteome of the subspecies V. ammodytes ammodytes (Vaa) from Serbia for the first time using the shotgun proteomics approach and identified 99 proteins belonging to four enzymatic families: serine protease (SVSPs), L-amino acid oxidase (LAAOs), metalloproteinases (SVMPs), group II phospholipase (PLA2s), and five nonenzymatic families: cysteine-rich secretory proteins (CRISPs), C-type lectins (snaclecs), growth factors -nerve (NGFs) and vascular endothelium (VEGFs), and Kunitz-type protease inhibitors (SPIs). Considerable enzymatic activity of LAAO, SVSPs, and SVMPs and a high acidic PLA2 activity was measured implying potential of Vaa to produce haemotoxic, myotoxic, neuro and cardiotoxic effects. Moreover, significant antimicrobial activity of Vaa venom against Gram-negative (Klebsiella pneumoniae, Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus) was found. The crude venom shows considerable potential cytotoxic activity on the C6 and HL60 and a moderate level of potency on B16 cell lines. HeLa cells showed the same sensitivity, while DU 145 and PC-3 are less sensitive than as normal cell line. Our data demonstrated a high complexity of Vaa and considerable enzymatic, antibacterial and cytotoxic activity, implying a great medical potential of Vaa venom as a promising source for new antibacterial and cytostatic agents.

Targeted isolation of terpenoid indole alkaloids from Melodinus cochinchinensis (Lour.) Merr. using molecular networking and their biological activities

Melodinus cochinchinensis (Lour.) Merr. has been used in Traditional Chinese Medicine for the management of various ailments, yet its chemical constituents are rarely studied. This study was aimed to isolate terpenoid indole alkaloids (TIAs) from the aerial parts of M. cochinchinensis by the guidance of ultrahigh-performance liquid chromatography coupled with a tandem mass spectrometry (UHPLC-MS/MS), and to elucidate their cytotoxic, immunosuppressive and anti-inflammatory activities. Eight new TIAs (1 and 5-11) along with 21 previously described analogues were isolated with the basis of molecular networking developed by our previously reported TIAs from the species of Melodinus. The structures of new TIAs were elucidated by the analysis of extensive spectroscopic data. Among the tested isolates, 11-methoxytabersonine (25) exhibited considerable cytotoxic activity against human acute lymphoblastic leukemia (MOLT-4), breast adenocarcinoma (MCF-7), pro-myeloid leukemia (HL-60), lung adenocarcinoma (A-549), and hepatocelluar carcinoma (SMMC-7721) cell lines, which was more effective than the positive control, cisplatin. The 19β-hydroxyvenalstonidine (21) displayed moderate immunosuppressive effect against Con A-induced splenocyte proliferation at 40 μM, while 16,17-dehydro-19S-vindolinine (1) showed potent inhibitory activity on nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expressions in LPS-induced RAW 264.7 macrophages.

Two New Taxane Diterpenoids From Taxus baccata

Two new diterpenoids named 13-oxo-wollifoliane-10,15-olide (1) and 19-acetoxy-7,9,10-deacetyl-baccatin VI (2), along with 14 known taxanes (3-16), were isolated from Taxus baccata. The structures of these compounds were elucidated by 1-dimensional and 2-dimensional nuclear magnetic resonance spectra, high-resolution electrospray ionization-mass spectrometry, and infrared spectroscopy. Structurally, 13-oxo-wollifoliane-10,15-olide (1) is the first taxane diterpenoid possessing an unusual carbonyl group at the C-13 position of the 11(15→1),11(10→9)bis- abeo-taxane structure (5/6/6/6/4 skeleton), and 19-acetoxy-7,9,10-deacetyl-baccatin VI (2) is a new compound containing an acetoxy group at the C-19 position of 6/8/6/4-taxane. Among the 14 known taxane compounds 3-16, compounds 7 and 9 were first isolated and reported from T. baccata. Several compounds (3-16) were evaluated for cytotoxicity against MCF-7 and HCT116 human cancer cell lines, but none of them showed considerable cytotoxic activity.

Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy.

SummaryIn some malignant tumor, especially for pancreatic tumor, poor solid-tumor penetration of nanotherapeutics impedes their treatment efficacy. Herein, we develop a polymer-peptide conjugate with the deep tissue penetration ability, which undergoes a cascade process under ultrasound (US), including (1) the singlet oxygen 1O2 is generated by P18, (2) the thioketal bond is cleaved by the 1O2, (3) the departure of PEG chains leads to the in situ self-assembly, and (4) the resultant self-assembled PK nanoparticles show considerable cellular internalization. Owing to the synergistic effect of US on increasing the membrane permeability, the endocytosis and lysosome escape of PK nanoparticles are further enhanced effectively, resulting in the improved therapeutic efficacy. Thanks to the high tissue-penetrating depth and spatial precision of US, PTPK presents enhanced tumor inhibition in an orthotopic pancreatic tumor model. Therefore, the US-activated cascade effect offers a novel perspective for precision medicine and disease theranostics.

Cytotoxic and Antiradical Activities of Extracts of Rhizopora apiculata (L)

The petroleum ether and methanol crude extracts of Rhizopora apiculata (L) (Rhizoporaceae) were screened for cytotoxicity by MTT bioassay and antioxidant activity using three different methods. The active constituents of the plant Rhizopora apiculata (L) were extracted using petroleum ether and methanol. Both extracts were tested for cytotoxicity by MTT assay at a concentration range of 18.75, 37.5, 100, 150 and 300μg/ml. The percentage cell viability shown in Pet ether extract for human cervical adenocarcinoma cell lines (HeLa), human osteosarcoma cell lines (MG 63) and Breast adenocarcinoma (MC 67) were in the range of 102-91%, 100-84% and 101-78% respectively shows that pet ether extract does not have considerable cytotoxic activity. On the other hand, Petroleum ether and methanol crude extracts of Rhizopora apiculata (L) showed mild antioxidant activity with compared to ascorbic acid.

Synthesis, cytotoxic evaluation, and molecular docking studies of some new 1, 3, 4-oxadiazole-based compounds.

Background and purpose:Oxadiazole-derived compounds have been shown to have a wide range of pharmacological activities. 2, 5-Disubstituted 1, 3, 4-oxadiazole derivatives have occupied a specific place in the design of anti-proliferative agents. In the present work a series of 2, 5-disubstituted 1, 3, 4-oxadiazoles derivatives containing amide group has been synthesized via a two-step reaction.Experimental approach:A mixture of substituted carboxylic acid derivatives, semicarbazide, and phosphorus oxychloride in reflux condition yielded 2-amino-5-aryl-1, 3, 4-oxadiazole derivatives. Acylation of the amino group of the resultant oxadiazole with 6-chloronicotinoyl chloride in dry tetrahydrofuran/pyridine afforded the final products. The synthesized molecules were docked in the active sites of the epidermal growth factor receptor tyrosine kinase domain (PDB: 1M17) crystal structure to study the possible interactions with the active site. Cytotoxic activities of final products against HeLa and MCF-7 cells were also assessed by MTT assay.Findings/Results:Compounds IIb, IIc, and IIe had a considerable cytotoxic activity with IC50 values of 19.9, 35, and 25.1 μM, respectively against HeLa cells. The highest docking score was -7.89 kcal/mol for compound IIe.Conclusion and implications:Compound IIe exhibited remarkable cytotoxic activity against the two tested cell lines particularly HeLa cells which was in accordance with the in silico ΔG bind result but further evaluations are necessary to prove these findings.

Isolation, Absolute Configuration and Cytotoxic Activities of Alkaloids from Hippeastrum goianum (Ravenna) Meerow (Amaryllidaceae)

The phytochemical study of Hippeastrum goianum led to the identification of 13 compounds by means of gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR). Compounds 7-demethoxy-9-O-methylhostasine (1) and 7-deoxi-trans-dihydronarciclasine (2) had their absolute configurations determined by vibrational circular dichroism (VCD). This is the first time that compound 1 is described in the Amaryllidaceae family. The cytotoxicity of all isolated compounds was tested against colorectal carcinoma (HCT 116), breast carcinoma (MCF-7), and non-tumor human retinal pigment epithelium (RPE) cell lines. The half-maximum inhibitory concentration (IC50) of compound 2 against each cell line was equivalent to the positive control (doxorubicin), indicating a considerable cytotoxic activity.

1,3-Benzoxatiol-2-onas e 1,3-Benzotiazóis como Potenciais Agentes Anticâncer e Antimicrobianos

Over the years, cancer and infectious diseases appear among the leading causes of death worldwide. These data highlight the need for new prototypes to design more potent and selective chemotherapeutics as well as new and non-traditional antimicrobial agents. The main goal of this work was to evaluate some 1,3-benzoxathiol-2-one and 1,3-benzothiazole derivatives for their anticancer, antibacterial and antifungal activities. Derivatives were screened for in vitro anticancer activity against melanoma (SKMEL-19), ascitic fluid (AGP-01) and breast (MCF-7) cancer cell lines by MTT assay. The toxicity profile against erythrocytes and normal cells human fibroblast (MRC-5) was also evaluated. Besides that, in vitro Antimicrobial Screening Test (AST), Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC) assays were performed against Gram-positive and Gram-negative bacteria as well as against Candida species. All tests were performed according to CLSI protocols, using vancomycin, ciprofloxacin and ketoconazole as reference drugs. Derivative 6-methoxy-benzo[d][1,3]oxathiol-2-one ( 7 ) exhibited considerable cytotoxic activity (IC 50 = 3.3 μM) against SKMEL-19 and compound ( E )-4-((2-(benzo[d]thiazol-2-yl)hydrazono)methyl)benzene-1,2,3-triol) ( 16m ) showed good activity against all Candida species (MIC 8-32 µg mL -1 ). The ratio MBC/MIC of 16l and 16m derivatives classified them as bactericidal agents against Gram-positive bacteria. Compound 16 m presented fungistatic profile against Candida albicans and non- albicans species evaluated. Overall, the in vitro results pointed to the potential of derivatives 7 and 16m as new anticancer and antifungal prototypes, respectively, to be further explored as they also presented low toxicity profile.

Baicalin-induced Cytotoxicity and Apoptosis in Multidrug-resistant MC3/5FU Mucoepidermoid Carcinoma Cell Line

Background: Multidrug Resistance (MDR) is a serious hindrance to cancer chemotherapy and profoundly influences the clinical findings. Many Traditional Chinese Medicines (TCM) have been tested with the aim of developing effective resistance modulators or anticancer drugs to overcome the MDR of human cancers. Methods: The anticancer effect of baicalin on multidrug-resistant MC3/5FU (5-fluorouracil) cells was investigated by MTT test and xenografts in nude mice. Cell apoptosis was studied by transmission electron microscopy, Hoechst-33342 staining, DNA fragmentation detection, and flow cytometry. RT-PCR and Rhodamine 123 efflux assay was also used to detect its effect on ABC drug transporter proteins, ABCB1 (P-glycoprotein, P-gp) and ABCC1 (multidrug resistance protein 1, MRP1). Results: The results indicate that there was no significant effect of baicalin on ABC transporters expression or efflux function, although it induced potent growth inhibition in MC3/5FU cells. Flow cytometry, Hoechst 33342 staining and transmission electron microscope revealed that baicalin caused MC3/5FU cell death through the induction of apoptosis. It is demonstrated that baicalininduced apoptosis could be mediated by up-regulation of Bax and caspase-3 protein levels and downregulation of Bcl-2 protein levels. In addition, daily intraperitoneal injection of baicalin (100 and 200 mg/kg) for 2 weeks significantly inhibited the growth of MC3/5FU cells xenografts in nude mice. Conclusion: Our results suggest that baicalin possesses considerable cytotoxic activity in multidrug resistance MC3/5FU cells in vitro and in vivo.

Design, synthesis of novel (Z)-2-(3-(4-((3-benzyl-2,4-dioxothiazolidin-5-ylidene)methyl)-1-phenyl-1H-pyrazol-3-yl)phenoxy)-N-arylacetamide derivatives: Evaluation of cytotoxic activity and molecular docking studies

Abstract In an attempt to discover potential cytotoxic agents, a series of novel (Z)-2-(3-(4-((3-benzyl-2,4-dioxothiazolidin-5-ylidene)methyl)-1-phenyl-1H-pyrazol-3-yl) phenoxy)-N-arylacetamide derivatives 11a-n were synthesized in varied steps with acceptable reaction procedures with good yields and characterized by 1H NMR, 13C NMR, IR and ESI-MS spectra. All the novel synthesized derivatives were assessed for their cytotoxic activity against human breast cell line (MCF-7) with different concentration of 0.625 μM, 1.25 μM, 2.5 μM, 5 μM and 10 μM respectively. Biological evaluation assay results were displayed in terms of percentage of cell viability reduction and IC50 values. Most of the screened derivatives demonstrated moderate to promising cytotoxic activity. Some of the derivatives, particularly compound 11d and 11n have shown promising cytotoxic activity with IC50 values 0.604 μM and 0.665 μM compared to standard drug cisplatin and compounds 11a, 11e and 11g also have shown considerable cytotoxic activity and the rest of the derivatives have shown moderate activity. Furthermore, molecular docking calculations and ADME properties of the synthesized molecules are in effective compliance with the cytotoxic evaluation results.

Synthesis and Antiproliferative Activity of Isolongifolanone Pyrazoline Derivatives Inducing Intracellular ROS Accumulation

A series of new isolongifolanone pyrazoline derivatives were synthesized and characterized by 1H NMR and HRMS methods. The compounds were assessed for their antiproliferative activity against three cancer cell lines (MDA-MB-231, Hela, and HepG2 cells) in vitro. Most of the derivatives showed considerable cytotoxic activity to all three cancer cell lines. Among them, compound 400 exhibited excellent antiproliferative activity with IC50 values of 15.45, 18.52, and 34.4 μM for MDA-MB-231, Hela, and HepG2 cells, respectively. Further mechanistic studies indicated that compound 400 induced apoptosis in HepG2 cells by enhancing the accumulation of intracellular reactive oxygen species (ROS). In summary, we report the synthesis of a new pyrazoline derivative of isolongifolanone (compound 400) that potently induces apoptosis in HepG2 cells by enhancing intracellular ROS production.

Synthesis and antitumor activity of 2-isocamphanyl thiosemicarbazone derivatives via ROS-enhanced mitochondrial damage.

A series of novel 2-isocamphanyl thiosemicarbazone derivatives were synthesized and characterized by 1 H NMR, 13 C NMR, and HRMS. In in vitro anticancer activity, most derivatives showed considerable cytotoxic activity against four cancer cell lines (RPMI-8226, A549, MDA-MB-231, and HepG2 cancer cells) and showed low toxicity against human gastric mucosal cells (GES-1). Among them, compound 4h exhibited excellent antitumor activity against the tested cancer cells with IC50 values of 0.4, 1.1, 1.6, and 1.7μM for MDA-MB-231, RPMI-8226, A549, and HepG2, respectively. Further, mechanism studies indicated that compound 4h induced apoptosis in MDA-MB-231 cells through enhancing reactive oxygen species levels, inducing mitochondrial membrane potential decrease, and influencing the expression of Bax, Bcl-2, caspase-3, and caspase-9.

Synthesis and biological evaluation of thiolate gold(i) complexes as thioredoxin reductase (TrxR) and glutathione reductase (GR) inhibitors

Au(i) complexes with PPh2py and thiolate ligands are prepared. The complexes are shown considerable cytotoxic activities and those efficiently inhibit the TrxRs and GR.

Antimicrobial, antidermatophytic, and cytotoxic activities from Streptomyces sp. MER4 isolated from Egyptian local environment

BackgroundRecently, actinomycetes have attracted the attention of researchers worldwide. They can produce secondary metabolites with antibacterial, antifungal, antiviral, and antitumoral properties.ResultsStreptomyces sp. MER4 (accession no. KM099241) was isolated from the pyramid region, Giza, Egypt. This strain was previously mentioned for its ability to produce antidermatophytic bioactive metabolites. Scale-up fermentation and fractionation of the extract has been established using different solvents. The ethanol fraction exhibited a considerable antidermatophytic effect (19.8, 21.2, and 20.3 mm for Trichophyton mentagrophyes, Microsporum canis, and Microsporum gypseum, respectively), antimicrobial (10, 8, 7, 9, and 9 mm for Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, Bacillus subtilis, and Aspergillus niger, respectively), and cytotoxic activity (inhibition of 78.48%). Further purification of the ethanol fraction was done, and one promising compound was produced. This compound was intensely characterized and elucidated by studying its spectral date including nuclear magnetic resonance (NMR) and liquid chromatography mass spectroscopy (LC/MS). The produced compound was identified as JBIR-58 (salicylamide) derivative compound.ConclusionsStreptomyces sp. MER4 has been identified genetically and screened for its ability to produce bioactive compound with antibacterial antitumor and antidermatophytic agent. The scale-up fermentation, purification, and structure elucidation led to pure compound named salicylamide derivatives JBIR-58 from the fermentation broth of Streptomyces sp. MER4.

Five New Diterpenoids from the Seeds of Euphorbia lathyris

A new premyrsinane-type diterpenoid, premylanin (1), and four new lathyrane-type diterpenoids named Euphorbia Factors L30 -L33 (2-5) were isolated from the seeds of Euphorbia lathyris, together with thirteen known ones (6-18). Their structures were elucidated through spectroscopic analyses, including IR, UV, HR-ESI-MS, 1D- and 2D-NMR. The cytotoxicities of compounds 1-4 and 6-18 against HCT116, MCF-7, 786-0, HepG2 cell lines were evaluated, and compound 13 exhibited considerable cytotoxic activities with an IC50 values of 6.44, 8.43, 15.3, 9.32 μm, respectively.

Abstract 1675: Design and synthesis of novel tyrosine kinase enzyme inhibitors and evaluating their anti-colorectal cancer activity

Abstract Targeting tyrosine kinases is attracting considerable attention for cancer therapeutics, nonetheless colorectal cancer. Herein we rationally designed and synthesized a group of 4-(3-methoxy-5-methylphenyl)-5-(pyridine-4-yl)pyrimidine-2-amine derivatives as potential inhibitors for tyrosine kinase. Synthesized compounds share a general structure and vary in substituents at position-2 of the terminal pyridine ring. The hydroxy-analogue of each methoxy derivative was also prepared to evaluate the effect of the methoxy group, at the phenyl ring in position-4 of the pyrimidine moiety, on activity. Compounds 1 (2-chloropyridyl and methoxyphenyl), 2 (2-chloropyridyl and hydroxyphenyl), 3 (2-(pyridine-3-yl)pyridyl and methoxyphenyl), 4 (2-(pyridine-3-yl)pyridyl and hydroxyphenyl), 5 (2-phenylpyridyl and hydroxyphenyl), 6 (2-(4-cyanophenyl)pyridyl and hydroxyphenyl) and 7 (2-(4-acetylphenyl)pyridyl and hydroxyphenyl) showed 29% to 79% tyrosine kinase inhibitory activity. Yet, cytotoxicity of all compounds were assessed against colorectal cancer cells (HT29 and HCT116) using SRB assay. Any compound (at 10 μM concentration) induced considerable viability drop was further assessed using detailed dose response curve and its cytotoxic parameters were calculated. Compounds 8 (2-(4-(N,N-dimethylamino)phenyl)pyridyl and hydroxyphenyl), 5, 6 and 7 showed considerable cytotoxic activities against HCT116 cells with IC50's of 9.18, 10.37, 9.47 and 16.60 μM, respectively. In addition, compounds 9 (2-chloropyridyl, methoxyphenyl and free 2-amino), 2, 3, 4, 5 and 6 showed considerable cytotoxicity against HT29 cells with IC50's of 9.31, 7.48, 11.26, 6.37, 9.89 and 7.14 μM, respectively. The mechanisms of cell killing effect of compounds with considerable anti-proliferative/cytotoxic activity were further assessed using cell cycle analysis (DNA content flowcytometry) and Annexin-V/FITC apoptosis assessment. Compound 2 induced antiproliferative effect which might be attributed to induction of cell cycle arrest at the G0/G1 phase; cell population in G0/G1 phase after treatment with compound 2 was 59.7±0.7% compared to 53.4±1.6% for control untreated cells. Compounds 4, 5, 6 and 7 induced significant cell cycle arrest at G2/M phase with cell populations equals 25.1±0.6%, 24.8±0.4%, 24.0±0.7% and 25.9±0.1%, respectively, compared to 19.3±1.6% for control untreated cells. Cell cycle arrest induced by compounds 1, 2, 3, 4, 6 and 7 resulted in significant apoptosis in colorectal cancer cells. In conclusion, this group of tyrosine kinase inhibitors showed promising anti-proliferative/cytotoxic effects in colorectal cancer cell lines attributed to cell cycle arrest. Further studies for the different cell cycle check point proteins and kinases are undergoing to clarify the exact underlying mechanism of cell killing attributed to each one of these compounds. Citation Format: Hanan A. Assiri, Hawazen A. BinMahfouz, Fahad A. Alabbasi, Marc Devocelle, Ibrahim M. El-deeb, Ahmed M. Al-Abd. Design and synthesis of novel tyrosine kinase enzyme inhibitors and evaluating their anti-colorectal cancer activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1675.

Inhibitory Effects of Silica Nanoparticles Loaded with Hematoporphyrin on Breast Cancer Cell Line

Background: Cancer is one of the main causes of death in the world. In recent years, many studies have been conducted on the usage of nanomaterials in cancer treatment. In previous studies, the anti-tumor effects of mesoporous silica nanoparticles (MSN) on cancer cells have been shown. The aim of this study was to evaluate the effect of MSN loaded with Hematoporphyrin (HpD) on the cell proliferation and invasion of MCF7 (Michigan Cancer Foundation-7) breast cancer cell line. The antioxidant effects of MSN loaded with HpD were also investigated. Methods: In this study, using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, the proliferation and viability of cancer cells were studied after exposure to MSN loaded with HpD. The wound healing assay technique (migration test) was used for the assessment of cancer cells’ invasion. The antioxidant effects of MSN loaded with HpD were studied by DPPH (2,2-diphenyl-1-picrylhydrazyl) assay and FRAP (ferric reducing/antioxidant power) assay techniques. Results: Our results showed that the viability and proliferation of breast cancer cell line MCF7 in the presence of silica nanoparticles loaded with hematoporphyrin (HpD) significantly declined (P = 0.02). After exposure to mesoporous silica nanoparticles (MSN) loaded with hematoporphyrin (HpD), the cancer cell invasion decreased (P = 0.025). Silica nanoparticles alone and loaded with hematoporphyrin (HpD) showed considerable cytotoxic activities against cancer cell lines (IC50 = 20 - 30 μg.mL-1). The most promising result was achieved for MSN loaded with hematoporphyrin (HpD) with the minimum IC50 value. It was found that the proliferation rate of MCF7 cells decreased after treatment with this compound in a dose-dependent manner. The assessments with DPPH assay and FRAP assay techniques showed that MSN and MSN loaded with HpD have antioxidant activities. Conclusions: MSN loaded with HpD have an inhibitory effect on the growth of the MCF7 cell line. MSN alone and in combination with HpD have an inhibitory effect on cell invasion in the MCF7 cell line. MSN alone and loaded with HpD have antioxidant effects. These results indicate that MSN has the potential to be used in cancer treatment as a carrier for anticancer drugs. Keywords: Silica Nanoparticles; Hematoporphyrin; Cell Viability; Invasion; Antioxidant; Breast Cancer; Cell Line

Four New Diterpenoid Alkaloids from the Roots of Aconitum carmichaelii

Aconitum carmichaelii Debeaux is a widely used traditional Chinese medicine and an important source of clinical drugs, of which the parent and lateral roots are known as 'Chuanwu' and 'Fuzi', respectively. Four new C19 -diterpenoid alkaloids, carmichasines A - D (1 - 4), were isolated from the roots of Aconitum carmichaelii, together with twelve known compounds (5 - 16). Their structures were elucidated via spectroscopic analyses, including HR-ESI-MS, IR, and NMR. Carmichasine A (1) is the first natural C19 -diterpenoid alkaloid possessing a cyano group. Most of the diterpenoid alkaloids isolated were C19 -category, which might provide further clues for understanding the chemotaxonomic significance of this plant. The cytotoxicity of the new compounds was also investigated against several human cancer cell lines, including MCF-7, HCT116, A549, and 786-0, and none of them showed considerable cytotoxic activity.

L-Amino acid oxidase from Cerastes vipera snake venom: Isolation, characterization and biological effects on bacteria and tumor cell lines

A homodimeric l-amino acid oxidase enzyme (Cv-LAAOI) was isolated from the venom of Cerastes vipera (Egyptian Sand viper) using gel filtration followed by anion exchange chromatography. The molecular mass of Cv-LAAO is 120 kDa in its native form and 60 kDa in its monomeric form. The optimum enzyme activity was achieved on l-Leucine as a substrate in 50 mM buffer pH 7.5 at 50 °C. The Cv-LAAOI activity was significantly reduced by increasing the temperature over 40 °C, lost 75% of its activity at 60 °C and inhibited completely at 80 °C. The Cv-LAAOI attains the highest substrate specificity towards L-Met. The results have also indicated that Mn2+ enhances the enzyme activity by 10%, while Cu2+, Hg2+, Ni2+, Co2+ have suppressive effects on the Cv-LAAOI activity. On the other hand, EDTA has no significant effect on the enzyme activity. The kinetic parameters of Cv-LAAOI activity (Km, Kcat and Vmax) estimated on l-Leucine at pH 8 and 37 °C were found to be 2 mM, 12 S−1 and 16.7 μmol/min/ml, respectively. In addition, the results have shown that Cv-LAAOI exhibits a significant bactericidal activity against gram-positive and gram-negative bacteria, particularly Staphylococcus aureus and Escherichia coli with MIC values of 20 μg/ml. Moreover, Cv-LAAOI has exhibited a considerable cytotoxic activity against breast cancer cell line (MCF-7) with IC50 value 2.75 ± 0.38 μg/ml compared with different tumor cell lines (liver HepG2, lung A549, colon HCT116 and prostate PC3). Furthermore, Cv-LAAOI has triggered antiproliferative activity via extensive H2O2 generation as indicated by the increase in H2O2 and TBARS levels accompanied by the depletion in the catalase activity (CAT) in MCF-7 treated cells compared to the untreated ones. Thus, these findings clearly indicate that Cv-LAAOI has a selective cytotoxic effect on breast cancer cell line, demonstrating a great prospective for future use in cancer therapy.