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A new series of urea and thiourea derivatives containing benzimidazole group as potential anticancer agents have been designed and synthesized. The structures of the synthesized compounds were characterized and confirmed by spectroscopic techniques such as 1H NMR, 13C NMR, and mass spectrometry. In vitro anticancer assay against two breast cancer (BC) cell lines, MDA-MB-231ER(−)/PR(−) and MCF-7ER(+)/PR(+), revealed that the cytotoxicity of 1-(2-(1H-benzo[d]imidazol-2-ylamino)ethyl)-3-p-tolylthiourea (7b) and 4-(1H-benzo[d]imidazol-2-yl)-N-(3-chlorophenyl)piperazine-1-carboxamide (5d) were higher in MCF-7 with IC50 values of 25.8 and 48.3 µM, respectively, as compared with MDA-MB-231 cells. Furthermore, 7b and 5d were assessed for their apoptotic potential using 4′,6-diamidino-2-phenylindole, acridine orange/ethidium bromide staining, and Caspase-3/7. After incubation with MCF-7, the compounds 7b and 5d induced apoptosis through caspase-3/7 activation. In conclusion, the compounds 7b and 5d are potential candidates for inducing apoptosis in different genotypic BC cell lines.

Liver diseases are particularly severe health problems, but the options available for preventing and treating them remain limited. Accumulating evidence has shown that there is altered expression of individual histone deacetylase (HDAC) family members in hepatocellular carcinoma cells. In a previous study, we have identified a set of proteins which interact with histone deacetylase 1 and 3 (HDAC1/3) in hepatocellular carcinoma cell lines HepG2 by proteomic approach. This study was designed to investigate the therapeutic potential and expression of HDAC1/3-interacting genes in a human hepatocellular carcinoma cell line (HepG2). Pharmacological and transcriptional inhibition of HDAC1/3 resulted in the suppression of cancer cell proliferation, change of cell morphology, and downregulation of HDAC1/3 genes in HepG2 cells. The pharmacological inhibition also resulted in inhibition of liver cancer cell migration by wound scratch assay. Taken together, the results from this study show that the upregulation of HDAC1/3 in hepatocellular carcinoma resulted in the overexpression of CNOT1, PFDN2/6, and HMG20B, and that these genes could serve as novel molecular targets in liver cancer.

Natural antiangiogenic products interact with multiple molecular angiogenic pathways and possesses comparably less toxicities then chemically synthesized anti-angiogenic compounds. There is a need to screen varieties of medicinal plants to identify more sources of antiangiogenic compounds, as anticancer drugs with less side effects. This study was designed to explore the antiangiogenic property and cytotoxicity of Moricandia sinaica (Boiss.) in zebrafish embryos, as well as its anti-migratory potential in human umbilical vein endothelial cells (HUVECs). Gas chromatography coupled with mass spectrophotometry was performed in order to identify bioactive molecules present in the stem and leaves part of Moricandia sinaica.The methanol extract of the stem and leaves inhibited the formation of the inter-segmental, sub-intestinal vein, and dorsal longitudinal anastomotic veins formation in zebrafish embryos in a dose- dependent manner. It did not show cytotoxicity at lower concentration in HUVECs; however, it significantly (p

Von Willebrand A domain-containing protein 8 (VWA8), also named KIAA0564, is a poorly characterized, mitochondrial matrix-targeted protein having a putative ATPase activity. VWA8 is comprising of ATPase-associated domains and a VWFA domain associated with ATPase activity inside the cell. In the present study, we describe a large consanguineous family of Saudi origin segregating a complex developmental syndrome in an autosomal recessive fashion. All the affected individuals exhibited severe developmental disorders. DNA from three patients was subjected to whole-exome sequencing followed by Sanger sequencing. VWA8 knock-down zebrafish morpholinos were used to study the phenotypic effect of this gene on zebrafish development. A homozygous missense variant [c.947A > G; p.(Asp316Gly)] was identified in exon 8 of the VWA8 gene, which perfectly segregated with the disease phenotype. Using zebrafish morpholino, we observed delayed development at an early stage, lack of movement, light sensitivity, severe skeletal deformity such as scoliosis, and facial dysmorphism. This is the first homozygous variant identified in the VWA8 gene underlying global developmental delay, microcephaly, scoliosis, limbs, and cardiovascular malformations in humans. We provide genetic and molecular evidence using zebrafish morpholino for a homozygous variant in the VWA8 gene, associated with such a complex developmental syndrome in humans.

The new asperorlactone (1), along with the known illudalane sesquiterpene echinolactone D (2), two known pyrones, 4-(hydroxymethyl)-5-hydroxy-2H-pyran-2-one (3) and its acetate 4, and 4-hydroxybenzaldehyde (5), were isolated from a culture of Aspergillus oryzae, collected from Red Sea marine sediments. The structure of asperorlactone (1) was elucidated by HR-ESIMS, 1D, and 2D NMR, and a comparison between experimental and DFT calculated electronic circular dichroism (ECD) spectra. This is the first report of illudalane sesquiterpenoids from Aspergillus fungi and, more in general, from ascomycetes. Asperorlactone (1) exhibited antiproliferative activity against human lung, liver, and breast carcinoma cell lines, with IC50 values &lt, 100 µM. All the isolated compounds were also evaluated for their toxicity using the zebrafish embryo model.

Background Bitter gourd (Momordica charantia) has attracted the focus of researchers owing to its excellent anti-diabetic action. The beneficial effect of Momordica charantia on heart has been reported by in vitro and in vivo studies. However the developmental toxicity or potential risk of M. charantia on fetus heart development is largely unknown. Hence this study was designed to find out the developmental toxicity of M. charantia using zebrafish (Danio rerio) embryos. Methods The crude extracts were prepared from fruit and seeds of M. charantia. The Zebrafish embryos were exposed to serial dilution of each of the crude extract. The biologically active fractions were fractionated by C18 column using high pressure liquid chromatography. Fourier-transform infrared spectroscopy and gas chromatography coupled with mass spectrophotometry was done to identify chemical constituents in fruit and seed extract of M. charantia. Results The seed extract of M. charantia was lethal with LD50 values of 50 μg/ml to zebrafish embryos and multiple anomalies were observed in zebrafish embryos at sub-lethal concentration. However, the fruit extract was much safe and exposing the zebrafish embryos even to 200 μg/ml did not result any lethality. The fruit extract induced severe cardiac hypertrophy in treated embryos. The time window treatment showed that M. charantia perturbed the cardiac myoblast specification process in treated zebrafish embryos. The Fourier-transform infrared spectroscopy analyses revealed diverse chemical group in the active fruit fraction and five new type of compounds were identified in the crude seeds extract of M. charantia by gas chromatography and mass spectrophotometry. Conclusion The teratogenicity of seeds extract and cardiac toxicity by the fruit extract of M. charantia warned that the supplementation made from the fruit and seeds of M. charantia should be used with much care in pregnant diabetic patients to avoid possible damage to developing fetus. Electronic supplementary material The online version of this article (10.1186/s12906-019-2599-0) contains supplementary material, which is available to authorized users.

s-Triazine is considered a privileged structure, as it is found in several FDA-approved drugs. In the framework of our ongoing medicinal chemistry project based on the use of s-triazine as a scaffold, we synthesized a series of mono- and di-pyrazolyl-s-triazine derivatives and tested them against four human cancer cell lines, namely Human breast carcinoma (MCF 7 and MDA-MB-231), hepatocellular carcinoma (HepG2), colorectal carcinoma (LoVo), and leukemia (K562). The cell viability assay revealed that most of the s-triazine compounds induced cytotoxicity in all four types of human cancer cell lines, however, compounds 4a, and 6g, both of them have a piperidine moiety in their structure were most effective. These two compounds affected the cell viability of cancer cells, with IC50 values within the range between 5 to 9 µM. The cell cycle analysis showed that 4a and 6g induced S and G2/M phase cell cycle arrest in K562 cells. This could be the mechanism by which these molecules induced cytotoxicity in tested cancer cells. The prepared compounds were tested in zebrafish embryos to evaluate in vivo and developmental toxicity of the pyrazolyl-s-triazine derivatives in animals. None of the derivatives were lethal in the concentration range tested.

Several derivatives containing morpholine/piperidine, anilines, and dipeptides as pending moieties were prepared using s-triazine as a scaffold. These compounds were evaluated for their anticancer activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231), a colon cancer cell line (HCT-116), and a non-tumorigenic cell line (HEK 293). Tamoxifen was used as a reference. Animal toxicity tests were carried out in zebrafish embryos. Most of these compounds showed a higher activity against breast cancer than colon cancer. Compound 3a—which contains morpholine, aniline, and glycylglycinate methyl ester—showed a high level of cytotoxicity against MCF-7 cells with IC50 values of less than 1 µM. This compound showed a much lower level of toxicity against the non-tumorigenic HEK-293 cell line, and in the in vivo studies using zebrafish embryos. Furthermore, it induced cell cycle arrest at the G2/M phase, and apoptosis in MCF-7 cells. On the basis of our results, 3a emerges as a potential candidate for further development as a therapeutic drug to treat hormone receptor-positive breast cancer., The work was funded in part by the National Research Foundation (NRF) (# 105892 and Blue Sky’s Research Programme # 120386). This study was funded by the Deanship of Scientific Research, King Saud University, through the Vice Deanship of Scientific Research Chairs.

The present protocol describes the synthesis of di and tri-substituted s-triazine derivatives•s-Triazine undergoes sequential nucleophilic substitution reaction but order of nucleophile is very crucial.•It is very difficult to substitute any nucleophile except amine once amine is incorporated onto s-triazine.•During the synthesis of O,N-type substituted s-triazine, always O-type should be incorporated first., Graphical abstract Image, graphical abstract

Background: Medicinal plants have been used in traditional medicine for the treatment of numerous diseases worldwide. There is a dire need for new anticancer agents and plants used in traditional medicine are a particularly useful source. Materials and methods: In this study, extracts of five different plants that grow in the desert of Saudi Arabia were evaluated to assess their cytotoxicity against the MDA-MB-231 breast cancer cell line. Soxhlet extraction was carried out on the leaves and stems using different solvents. The cytotoxicity of these extracts against MDA-MB-231 breast cancer cells was assessed using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. The apoptotic cellular morphological changes were observed using inverted and fluorescence microscopes. Results: Our results showed that two of the five different medicinal plants (Rumex vesicarius and Malva parviflora) exhibited strong anticancer activity against the breast cancer cells. Specifically, 2 of the 40 extracts (from the five studied plants) showed promising activity. The chloroform extract of the stem of R. vesicarius (RSV CHCL3) exhibited moderate anticancer activity with a half-maximal inhibitory concentration (IC50) of 230 µg/mL while that of the hexane extract of M. parviflora stems (MPS Hex) was 248 µg/mL. Loss of cell integrity, shrinkage of the cytoplasm, and cell detachment were observed in the extract-treated MDA-MB-231 cells. Conclusion: R. vesicarius and M. parviflora chloroform and n-hexane stem extracts showed significant cytotoxicity against MDA-MB-231 human breast carcinoma cells.

This study aimed to isolate and identify moulds from rotten Citrus sinensis post-harvests and to investigate the activity of antagonist and biocontrol activity moulds that cause citrus fruit rotting. A total of 12 mould isolates were obtained. Following the pathogenicity test, two representative mould isolates were selected and identified based on the sequence analyses of internal transcribed spacer (ITS) regions of the rDNA. Methods used in this study include isolation of fungal postharvest diseases, pathogenicity assay, antagonism assay, growth curve analysis, in vitro biocontrol assay, and molecular phylogenetic analysis. Two isolates of fungal postharvest diseases were determined as the most destructive pathogens. The biocontrol assay showed that isolates of Y1 and Y10 were capable to reduce the growth of fungal isolates K6 and K9 and mitigate up to 100% of the damage of sweet citrus fruits after 7 days of incubation. The moulds were identified as K6 (Aspergillus flavus sensu lato) and K9 (Aspergillus niger sensu lato). Phylogenetic analysis showed that the Y10 yeast isolate was identified as Candida orthopsilosis, whereas the Y1 isolate had a close genetic relationship with Aureobasidium pullulans and possibly belongs to a new species. Further analysis is necessary to confirm this finding.

Background Rhazya stricta Decne. is a medicinal plant that is widespread in Saudi Arabia and desert areas of the Arabian Peninsula. Its extract contains alkaloids, tannins, and flavonoids that are involved in different biological activities. The study aim was to evaluate the effects of Rhazya stricta plant extracts on the proliferation and differentiation of NTERA-2 (NT2) pluripotent embryonal carcinoma cells. Methods Soxhlet extraction was carried out using different solvents to extract stems, leaves and fruit parts of this plant. Cytotoxicity was evaluated by an MTS cell viability assay. The ability of the plant extract to induce cell differentiation was examined phenotypically using an inverted light microscope. The expression of pluripotency markers was investigated by reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry. Phytochemical screening of chloroform stem extracts was carried out and a chromatographic fingerprint was generated using gas chromatography – mass spectrometry (GC-MS). Results Chloroform stem extract induced differentiation of NT2 cells at 5 μg/ml, and the differentiated cells exhibited neurite formation. Following induction of differentiation, there was significant down-regulation of the pluripotency marker genes Oct4 and Sox2. In addition, the surface antigen pluripotency marker, TRA-1-60, was strongly down-regulated. Phytochemical analysis of the extract showed the presence of alkaloids and saponins. The chromatogram revealed the presence of fifteen compounds with different retention times. Conclusion Our results demonstrate for the first time that chloroform stem extract of R. stricta can induce neuronal differentiation of stem cells at an early stage and may contain potential therapeutic agent that can be used in neurodegenerative diseases.

Recent trends in anticancer therapy is to use therapeutic agents which not only kill the cancer cell, but are less toxic to surrounding normal cells/tissue. One approach is to cut the nutrient supply to growing tumor cells, by blocking the formation of new blood vessels around the tumor. As the phytochemicals and botanical crude extracts have proven their efficacy as natural antiangiogenic agents with minimum toxicities, there is need to explore varieties of medicinal plants for novel antiangiogenic compounds.Rumex vesicarius L. (Humeidh), is an annual herbal plant with proven medicinal values. The antiangiogenic potential, and developmental toxicity of humeidh in experimental animal models has never been studied before. The crude extracts were prepared from the roots, stems, leaves and flowers of Rumex vesicarius L. in methanol, chloroform, ethyl acetate and n-hexane. The developmental toxicity screening in zebrafish embryos, has revealed that Rumex vesicarius was not toxic to zebrafish embryos. The chloroform stem extract showed significant level of antiangiogenic activity in zebrafish angiogenic assay on a dose dependent manner. Thirty five (35) bioactive compounds were identified by gas chromatography mass spectrophotometry (GC–MS) analysis in the stem extract of Rumex vesicarius. Propanoic acid, 2-[(trimethylsilyl)oxy]-, trimethylsilyl ester, Butane, 1,2,3-tris(trimethylsiloxy), and Butanedioic acid, bis(trimethylsilyl) ester were identified as major compound present in the stem of R. vasicarius.The anticancer activity of roots, stem, leaves and flowers crude extract was evaluated in human breast cancer (MCF7), human colon carcinoma (Lovo, and Caco-2), human hepatocellular carcinoma (HepG2) cell lines. Most of the crude extracts did not show significant level of cytotoxicity in tested cancer cells line, except, chloroform extract of stem which exhibited strong anticancer activity in all tested cancer cells with IC50 values in micro molar range.Based on these results, it is recommended that formulation prepared from R. vesicarius can further be tested in clinical trials in order to explore its therapeutic potential as an effective and safe natural anticancer product. Keywords: Rumex vasicarius L., Angiogenesis, Phytochemical screening, Developmental toxicity, Zebrafish embryos

Here we report on a small library based on a 4-aminobenzonitile-s-triazine moiety. We used a straightforward orthogonal synthetic pathway to prepare di- and tri-substituted s-triazine derivatives, whose basic structure was modified. The newly synthesized compounds were fully characterized by 1H NMR, 13C NMR and elemental analysis. They showed strong anticancer activity against two human breast cancer cell lines (MIDA-MB-231 and MCF-7), with IC50 values less than 1 µM. These s-triazine compounds were generally more selective towards hormone receptor-positive breast cancer cell line MCF-7 than the triple negative MDA-MB-231 cell line. Zebrafish embryos were used to test the developmental toxicity of the target compounds in vivo. The phenotype of embryos treated with the derivatives resembled that of those treated with estrogen disruptors. This observation strongly supports the notion that that these compounds induce their anticancer activity in human breast cancer cells via targeting the estrogen and progesterone receptors.

Resistance to chemotherapy and recurrence are major hurdles to treating hormone receptor-negative breast cancer. The crude extract and natural products obtained from medicinal plants are believed to be multitargeted and possess less toxicity as compared to synthetic compounds. The aerial parts and roots of Moricandia sinaica (Boiss.) Boiss were used to prepare the crude extracts in solvents of different polarities. Human breast cancer cell lines (MCF7 and MDA-MB-231), liver carcinoma (HepG2), and nontumorigenic cells of human origin (human umbilical vein endothelial cells (HUVEC)) were treated with a serial dilution of crude extracts obtained from the aerial and roots of Moricandia sinaica (Boiss.) Boiss. The methanol extract of the shoots exhibited a higher level of cytotoxicity against MDA-MB-231 cells than against any other cancer and nontumorigenic cells lines. Six new compounds were identified by gas chromatography–mass spectrophotometry analysis in the shoots extract of Moricandia sinaica (Boiss.) Boiss, and 2-Tridecen-1-ol was one of the major compounds that represent more than 35% of the extract. M-phase inducer phosphases 1 and 2 (CDC 25A and B) were identified as the specific protein target for 2-Tridecen-1-ol by the Swiss protein target prediction tool. In silico molecular docking showed the binding of 2-Tridecen-1-ol with CDC 25 B with a higher binding energy as compared to CDC 25A. The possible molecular mechanism of anticancer activity of Moricandia sinaica (Boiss.) Boiss in MDA-MB-231 breast cancer is through inhibition of M-phase inducer phosphatases 1 and 2 via 2-Tridecen-1-ol. Further investigations in breast cancer models are needed to explore the therapeutic potential of Moricandia sinaica (Boiss.) Boiss and 2-Tridecen-1-ol as an efficient remedy with a possibly less toxic approach to treat triple-negative breast cancer.

Eight novel N'-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a-h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32-50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC50 value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.

A first example of 5-component 5-center reactions with isonitriles [Ugi-5CRs] is described. The extended Ugi type reactions involve selenoaldehydes as well as ammonia, both challenging reactants in multicomponent (MCR) systems, to generate methionine and Se-methionine moieties and derivatives as protected building blocks or for direct ligation in peptides or peptoids. The peptoid/peptide building blocks proved to be non-cytotoxic but increased the expression of genes encoding for stress protective selenoproteins (Gpx1).

Background: Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. However, design and synthesis of chemical derivatives with improved antiangiogenic and anticancer activities are still necessary. In this study a library of novel derivatives of VPA was synthesized and tested. Methods: A human liver cancer cell line (HepG2) and a human normal embryonic kidney cell line (HEK 293) were exposed to various concentrations of VPA derivatives for 24 hours and cell viability was checked by MTT colorimetric assay. Anti-angiogenic properties were evaluated in transgenic zebrafish embryos. Results: N-valproylglycine derivatives suppressed survival almost 70% (p value 0.001) in HepG2 cells but only 10-12% in HEK 293 cells (p value 0.133). They also suppressed angiogenic blood vessel formation by 80% when used between 2-20 µM in zebrafish embryos. Valproic acid hydrazides showed moderate level of anticancer activity by affecting 30-50% (p value 0.001) of cell viability in HepG2 cells and 8-10% in HEK293 cells (p value 0.034). Conclusion: The majority of compounds in this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat hepatocellular carcinoma.

Aims: The study was designed to find out the protein complex(s) associated with HDAC3 in liver cancer using a modified form of affinity purification coupled with a mass spectrometry technique in HepG2 cells. The organ-specific requirement for HDAC1 and HDAC3 during liver formation in zebrafish and their altered expression in liver cancer tissues indicates they are indispensible for hepato-organogenesis and hepatocarcinogenesis. However, how they exert their function is unknown. Material & methods: HepG2 cells were transfected with either mock or construct-containing HDAC3 using a C-terminal strepIII–HA tag as bait. The bait proteins were purified by double affinity columns and were analyzed on a Thermo LTQ Orbitrap™ (Thermo Scientific, MA, USA) chromatography system. Results: Affinity purification coupled with mass spectrometry resulted in the identification of 24 putative binders of HDAC3 in HepG2 cells. The majority (83%) of these are novel interactions are reported for the first time in this study. Conclusion: This is the first study reporting the affinity purification and identification of protein complexes with two closely related proteins in one cell line. The novel HDAC1 and HDAC3 complexes identified in HepG2 cells could serve as a platform for the design of future therapeutic medicine for the treatment of liver cancer.

Background: Hepatocellular carcinoma is one of the leading causes of mortalities worldwide. The search for new therapeutic targets is of utmost importance for improved treatment. Altered expression of HDAC1 in hepatocellular carcinoma (HCC) and its requirement for liver formation in zebrafish, suggest that it may regulate key events in liver carcinogenesis and organogenesis. However, molecular mechanisms of HDAC1 action in liver carcinogenesis are largely unknown. The present study was conducted to identify HDAC1 interacting proteins in HepG2 cells using modified SH-double-affinity purification coupled with liquid mass spectrophotemetery. Materials and Methods: HepG2 cells were transfected with a construct containing HDAC1 with a C-terminal strepIII-HA tag as bait. Bait proteins were confirmed to be expressed in HepG2 cells by western blotting and purified by double affinity columns and protein complexes for analysis on a Thermo LTQ Orbitrap XL using a C18 nano flow ESI liquid chromatography system. Results: There were 27 proteins which showed novel interactions with HDAC1 identified only in this study, while 14 were among the established interactors. Various subunits of T complex proteins (TCP1) and prefoldin proteins (PFDN) were identified as interacting partners that showed high affinity with HDAC1 in HepG2 cells. Conclusions: The double affinity purification method adopted in this study was very successful in terms of specificity and reproducibility. The novel HDAC1 complex identified in this study could be better therapeutic target for treatment of hepatocellular carcinoma.

Human gastrointestinal microbiota (HGIM) incorporate a large number of microbes from different species. Anaerobic bacteria are the dominant organisms in this microbial consortium and play a crucial role in human health. In addition to their functional role as the main source of many essential metabolites for human health, they are considered as biotherapeutic agents in the regulation of different human metabolites. They are also important in the prevention and in the treatment of different physical and mental diseases. Bifidobacteria are the dominant anaerobic bacteria in HGIM and are widely used in the development of probiotic products for infants, children and adults. To develop bifidobacteria-based bioproducts, therefore, it is necessary to develop a large-scale biomass production platform based on a good understanding of the ideal medium and bioprocessing parameters for their growth and viability. In addition, high cell viability should be maintained during downstream processing and storage of probiotic cell powder or the final formulated product. In this work we review the latest information about the biology, therapeutic activities, cultivation and industrial production of bifidobacteria.

Three series of isatin derivatives [3-hydrazino, 3-thiosemicarbazino, and 3-imino carboxylic acid derivatives] were synthesized employing microwave irradiation. The prepared compounds were characterized by FT-IR, NMR, elemental analysis, and X-ray crystallography for derivatives5b. The synthesized compounds were screened for antimicrobial activity against selected bacteria and fungi. The results revealed that theN-alkyl isatin derivatives were biologically active with different spectrums activity. Most of the 3-hydrazino and 3-thiosemicarbazino isatin derivatives were biologically inactive and generally the active derivatives showed weak to moderate activity mainly against Gram-positive bacteria. The imino isatin carboxylic acid derivatives (2-[4-(1-benzyl-5-bromo-2-oxoindolin-3-ylideneamino) phenyl]acetic acid,5d) showed promising activity against all tested Gram-positive bacteria and against fungal pathogens.

Status epilepticus (SE) is a recurrent generalized convulsion condition and is regarded as a medical emergency with around 50% of the cases occurring in children. Besides neurobehavioral and motor deficits, SE is reportedly associated with imbalance in a number of neurochemicals in several areas of the brain. Furthermore, neuronal hyperactivity and/or excitotoxicity in such brain areas have been associated with excessive generation of free radicals. Proglumide (Pgm) is a known cholecystokinin (CCK) antagonist and any changes in the level of CCK and in the number of CCK receptors has been linked with SE. The present study was designed to investigate the possible neuroprotective effects of Pgm (0, 250, 500 and 750mg/ml/kg i.p.) on epileptic seizure activities, some neurobehavioral tests, and on some oxidative stress related parameters like lipid peroxides measured as thiobarbituric acid-reactive substance (TBARS) and total glutathione (GSH) in brain (hippocampus and striatum) of young rats that were experimentally induced with SE by lithium (Li) in 3mEq/ml/kg dose, i.p. followed 20h later by pilocarpine (Pc) in 20mg/ml/kg dose, s.c.). Besides significant anti-epileptic effect, Pgm significantly ameliorated SE-induced deterioration in cognitive behavior (in water-maze), motor performance (on rotarod), and biochemical changes in brain. It is concluded from the present study that Pgm has significant neuroprotective effects against SE and this effect may probably be due to its antioxidant activity. Pgm may prove to be a potentially effective antiepileptic drug, however, further studies are needed to ascertain this possibility.

For centuries, macrofungi have been used as food and medicine in different parts of the world. This is mainly attributed to their nutritional value as a potential source of carbohydrates, proteins, amino acids, and minerals. In addition, they also include many bioactive metabolites which make mushrooms and truffles common components in folk medicine, especially in Africa, the Middle East, China, and Japan. The reported medicinal effects of mushrooms include anti-inflammatory effects, with anti-inflammatory compounds of mushrooms comprising a highly diversified group in terms of their chemical structure. They include polysaccharides, terpenoids, phenolic compounds, and many other low molecular weight molecules. The aims of this review are to report the different types of bioactive metabolites and their relevant producers, as well as the different mechanisms of action of mushroom compounds as potent anti-inflammatory agents.

Background Monoclonal antibodies (Mabs) have been recently used for the treatment of virtually every debilitating disease. Packed-bed bioreactors have been used for the cultivation and production of a wide range of cell lines and biologics including MAbs. The principle behind a Packed-bed bioreactor is that the cells are being immobilized within a suitable stationary matrix which is represented by the bed. Packed-bed bioreactors also have the advantage of being capable of generating high cell densities with a low concentration of free cells in suspension; hence, simplifying downstream processing. The present work was designed to compare between the cultivation of hybridoma cells as well as the production of OKT3 MAb in free and immobilized culture conditions.

The present study was undertaken to assess the long-term consumption of the seeds of Nigella sativa L., also known as black seed and garlic by the female rats on the fecundity and gender ratio of their male and female offspring for two consecutive pregnancies, locomotory behavioural activities of offspring and on some important blood chemistry parameters of the offspring at adolescent age. The dose of black seed oil or garlic oil (0.8 ml per day) was administered orally and daily through gavage to the females until the weaning age offspring of second pregnancy. The offspring (at PD28 age) were subjected to the locomotory test and subsequently their serum analysis was done to measure the level of glutamic oxaloacetic transaminase (GOT or AST), glutamic pyruvic transaminase (GPT or ALT), cholesterol (HDLP), triglycerides (TG), and glucose (GLU). It was observed that black seed consumption increased the fecundity (total number of offspring) in both pregnancies. The number of male offspring increased significantly whereas the number of female offspring remained unaffected in both pregnancies. On the contrary, garlic showed no change in the sex ratio of offspring. Male offspring of the mothers consuming black seed oil were comparatively more active than the offspring of mothers consuming garlic oil. However, female offspring of mothers consuming both black seed and garlic oils were significantly active as compared to the controls. Black seed and garlic oil consumption by the mothers had a lowering effect on the level of TG, GOT, GPT and GLU in the serum of the offspring of both pregnancies, whereas no change was observed on the level of serum HDLP. Thus it is concluded that these two indigenous plant sources of herbal therapies may prove beneficial to the offspring if consumed by their mothers before and during pregnancies. However, further similar studies on larger sample of animals are warranted.