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Marine derived fungi are considered as a promising source of novel drugs due to their biodiversity and consequent chemo-diversity. Although marine microorganisms especially fungi are not well defined taxonomically, making this a promising frontier for the discovery of new medicines. This study focused on marine derived fungi as a model for bioactive exploration for new entities with anti-inflammatory and antioxidant capacity. Three in-vitro assays were used to investigate the bioactive antioxidant potentiality of fungal extracts. Thiobarbituric acid (TBARS), α,α-Diphenyl-ßpicrylhydrazyl (DPPH) and NO assay are based on their total phenolic and flavonoid content of each extract group. Ch. globosum recorded the highest antioxidant activity (92.82%) in TBARS assay, while G. dankaliensis came first by recording 59.28% in DPPH assay in comparison with ascorbic acid (61.83%). In NO inhibition assay, N. oryzae showed 49.3% comparing with ascorbic acid (73.12%). From the preliminary result of our extracts, we can consider the marine derived fungi extracts as promising antioxidant and anti-inflammatory drug candidate.

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Reaction of pyridin-2(1H)-one 1 with 4-bromobutylacetate (2), (2-acetoxyethoxy)methyl bromide (3) gave the corresponding nicotinonitrile O-acyclonucleosides, 4 and 5, respectively. Deacetylation of 4 and 5 gave the corresponding deprotected acyclonucleosides 6 and 7, respectively. Treatment of pyridin-2(1H)-one 1 with 1,3-dichloropropan-2-ol (8), epichlorohydrin (10) and allyl bromide (12) gave the corresponding nicotinonitrile O-acyclonucleosides 9, 11, and 13, respectively. Furthermore, reaction of pyridin-2(1H)-one 1 with the propargyl bromide (14) gave the corresponding 2-O-propargyl derivative 15, which was reacted via [3+2] cycloaddition with 4-azidobutyl acetate (16) and [(2-acetoxyethoxy)methyl]azide (17) to give the corresponding 1,2,3-triazole derivatives 18 and 19, respectively. The structures of the new synthesized compounds were characterized by using IR, (1)H, (13)C NMR spectra, and microanalysis. Selected members of these compounds were screened for antibacterial activity.

Novel quinuclidinone derivatives have been previously reported by our laboratory. In this study, we investigated the impact of two novel quinuclidinone derivatives 4 and 6 on apoptotic signaling in breast cancer cells (MCF-7) and their normal counterparts (MCF-12a). Our data revealed that derivatives 4 and 6 reduced proliferation and induced apoptosis in breast cancer cells. However, derivative 6 was less cytotoxic to normal breast epithelial cells than breast cancer cells; therefore, we focused on derivative 6 for further investigation. Flow cytometric analysis showed that quinuclidinone derivative 6 reduced the percentage of MCF-7 cells in G(2)/M which is confirmed by increased expression levels of cyclin B, while it arrests MCF12a in G1 phase judging from increased p21. Quinuclidinone derivative 6 increased expression levels of p53 and Bax at both protein and mRNA levels and reduced expression level of Mdm2, Bcl2, Akt and Bcl-XL It also increased mitochondrial apoptotic pathways by activating release of cytochrome c which is consistent with activation of caspase-9 as confirmed by caspase-9 inhibitor LEHD-CHO. Finally, it increased sphingomyelinase signaling and ceramide formation as well as its downstream targets ERK1/2, p38, and JNK. Inhibition of ERK1/2 with PD98059 exerted little effect on the derivative 6-induced apoptosis and p38 inhibition with SB203580 slightly lessened apoptosis, whereas inhibition of JNK with SP600125 markedly suppressed derivative 6-induced apoptosis. These results indicate that derivative-6 induced the activation of sphingomyelinase signaling and that JNK played a pivotal role in induction of apoptosis in human breast cancer cells. In vivo studies and molecular docking experiments are now in progress for further anticancer investigations.

Nucleic acids U 0700Novel Regioselective Hydroxyl-Alkylation of 4,5-Diphenylimidazole-2-thione and a Competitive Intramolecular Ring Closure of the S-Hydroxyalkyl-imidazoles to Imidazo[2,1-b]thiazines and Thiazoles. Role of Catalyst, Microwave Irradiation, and Solid Support. -For the preparation of acyclonucleoside analogues, the alkylation of imidazole derivatives (I) with alkanols (II) is carried out. The reaction proceeds regioselectively and under microwave irradiation in short time. The use of bentonite as solid support leads to similar results.Excess (II) leads to bisalkylated products. In the case of (Ic) imidazothiazine (IVc) is also formed which is obtained via ring closure of monoalkylated product (IIIc). -(EL ASHRY*, E. S. H.; RASHED, N.; AWAD, L. F.; RAMADAN, E.; ABDEL-MAGGEED, S. M.; REZKI, N.; Nucleosides, Nucleotides Nucleic Acids 26 (2007) 5, 423-435; Dep. Chem., Fac. Sci., Alexandria Univ., Alexandria 21321, Egypt; Eng.) -Schulze 47-199

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