A marine Bacillus subtilis SDNS was isolated from sea water in Alexandria and identified using 16S rDNA sequence analysis. The bacterium produced a compound active against a number of gram negativeve bacteria. Moreover, the anticancer activity of this bacterium was tested against three different human cell lines (Hela S3, HepG2 and CaCo). The highest inhibition activity was recorded against Hela S3 cell line (77.2%), while almost no activity was recorded towards CaCo cell line. HPLC and TLC analyses supported evidence that Bacillus subtilis SDNS product is ε-poly-L-lysine. To achieve maximum production, Plackett-Burman experimental design was applied. A 1.5 fold increase was observed when Bacillus subtilis SDNS was grown in optimized medium composed of g/l: (NH(4))(2) SO(4), 15; K(2)HPO(4), 0.3; KH(2)PO(4), 2; MgSO(4) · 7 H(2)O, 1; ZnSO(4) · 7 H(2)O, 0; FeSO(4) · 7 H(2)O, 0.03; glucose, 25; yeast extract, 1, pH 6.8. Under optimized culture condition, a product value of 76.3 mg/l could be obtained. According to available literature, this is the first announcement for the production of ε-poly-L-lysine (ε-PL) by a member of genus Bacillus.

A total of 17 actinomycetes were isolated and screened against five bacterial pathogens. Forty-one per cent of the isolates were active against the tested pathogens. The most potent isolate was identified as Streptomyces parvus by using a 16S rRNA sequence analysis. S. parvus produced active compound(s) against a number of Gram negative and Gram positive bacteria. The obtained inhibition zones were 14, 19, 20 and 20 mm against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Aeromonas hydrophila, respectively. Moreover, the anticancer activity of S. parvus was tested against four different cell lines: human liver cancer cell line, mouse lymphoma cell line, breast cancer cell line and human colon cancer cell line. The inhibition activities were 53%, 56%, 57% and 42%, respectively. To achieve a maximum production of the bioactive compound, PlackettÀBurman design was applied. The productivity increased up to 1.3-fold, when S. parvus was grown in optimized medium composed of: 10 g, 2 mL (10 3 colony-forming units mL ¡1 ) inoculum size with pH 8 for 7 d of incubation. The main constitutes of S. parvus crude extract were determined by gasÀliquid chromatography mass spectrometry. They were found to be ethane, 1,1-diethoxy; di-n-octyl phthalate; ethanol, 2,2-diethoxy; 9,12-octadecadienoic acid; methyl ester (E,E) and benzoic acid.

In this study, synthesis and docking studies of a series of new benzimidazole derivatives linked to substituted pyrimidines either through the methylenethio linkage or its bioisosteric methylene amino bridge were carried out. All the synthesized compounds were evaluated for their hepatitis C virus (HCV) RNA replication-inhibitory activity. Compounds 4d, 4f, and 4h were found to be more potent than VX-950 (IC 50/ Key words synthesis; benzimidazole; pyrimidine; hepatitis C virus; viral RNA replication inhibitor As estimated by WHO, 170 million persons worldwide are infected with hepatitis C virus (HCV) which causes chronic liver disease. HCV is a positive stranded RNA virus and is a member of the Flaviviridae family of viruses.1,2) Combined therapy of HCV infections with pegylated alpha interferon (IFN-α) and ribavirin is only effective in 50-60% of infected individuals and is associated with serious side effects such as depression, flu-like symptoms, fatigue and hemolytic anemia caused by ribavirin. 3,4)There is an unmet need for potent and selective inhibitors of HCV replication. Significant research efforts are currently directed towards targeting viral enzymes especially NS3-4A serine protease [5][6][7][8] and NS5B RNA-dependent RNA polymerase which are both required for virus propagation. 9-11)The NS3-4A serine protease has been an attractive target in the development of new antivirals with activities against HCV since it is essential for viral replication.9-11) The serine protease activity of NS3 in complex with the NS4A cofactor is responsible for the proteolytic cleavage at four junctions of the HCV polyprotein precursor: NS3-NS4A (self cleavage), NS4A-NS4B, NS4B-NS5A, and NS5A-NS5B. 7,[12][13][14][15][16][17] Crystal structure of the serine protease domain of the NS3, with its essential cofactor NS4A, 18,19) revealed that the NS3-4A complex adopts a chymotrypsin/trypsin-like fold with structurally conserved regions typical of small chymotrypsin-like proteases. 20,21) The N-terminal region of NS3-4A (residues 1-93 of NS3 and residues 21-34 of NS4A) contains an eightstranded β-barrel motif, with one of the strands contributed by the NS4A cofactor.20) The C-terminal region (residues 94-175) contains a six-stranded-barrel that ends with a helix. The active site (His: 57, Asp: 81, and Ser: 139) is located between these two regions and is formed by a shallow solvent exposed pocket to which the inhibitors bind in an extended conformation. 18-21)Sofosbuvir (GS-7977), a uridine nucleotide analogue, and an inhibitor of HCV NS5B polymerase is effective against HCV genotypes 1, 2, 3, 4, and 6. Sofosbuvir, especially in interferon-free combinations, represents a very promising option in the treatment of chronic hepatitis C. 22)Currently, different anti-HCV treatments depend on the inhibition of HCV NS3-4A serine protease. Telaprevir (VX-950), boceprevir and BILN 2061 (Fig. 1) are examples of well known HCV NS3-4A serine protease inhibtors. 23,24) Telaprevir, a small molecule peptidomimetic, forms a covalent but revers...

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