Molecular design, synthesis and cell based HCV replicon assay of novel benzoxazole derivatives.

Hepatitis C virus inhibitors based on benzoxazole scaffold were designed based on molecular modeling simulation study including docking into the NS5B polymerase active site. Several compounds showed significant high simulation docking scores relative to the assigned benzimidazole lead compound. The designed compounds were synthesized, structurally elucidated and their antiviral activity was evaluated through cell-based replicon in cultured Huh 5-2 cells. A number of the synthesized compounds showed significant inhibitory activity ranging from (52.2% inhibition up to 98% at<50 µg/mL). N-Benzyl-2-phenylbenzo[1,3]oxazole-5-carboxamide (8b) and N-Phenethyl-2-phenylbenzo[1,3] oxazole-5-carboxamide (8c) demonstrated genuine HCV inhibitory activity with EC50 values of 41.6 and 24.5 µg/mL respectively.

Palladacycles as antimicrobial agents.

This review article deals with the structure activity relationship (SAR) for a variety of palladacycles in biomedical applications. Moreover, the types of antibacterial, antifungal, antimycobacterial and antiprotozoal (antiamoebic and antitrypanosomal) activities will vary considerably from one country to another. Therefore, all efforts will be required to face such a vast diversity of problems. This study gives an up to date overview of the antibacterial, antifungal, antimycobacterial and antiprotozoal chemistry of the palladium group elements with an emphasis on the new strategies used in the development of new antibacterial agents. Methodologies for application of bulky aromatic or aliphatic nitrogen ligands, chiral organic moieties, chelates containing other donor atoms than nitrogen, and biologically active ligands in the design of agents analogous to palladacycles are presented. Therefore, the use of palladacycles in medicinal chemistry is interesting as potential application in the biological properties with less toxic drugs compounds..

Synthesis, docking studies and anti-inflammatory activity of some 2-amino-5,6,7,8-tetrahydroquinoline-3-carbonitriles and related compounds.

A series of 2-amino-5,6,7,8-tetrahydroquinoline-3-carbonitriles 4a-c has been synthesized and reacted with various reagents. Docking studies into the catalytic site of p38 mitogen activated protein kinase (MAPK) were used to identify potential anti-inflammatory lead compounds. The anticipated lead derivative 2-(pyridin-3-yl)-5-(4-methoxyphenyl)-6,7,8,9-tetrahydropyrimido[4,5-b]quinolin-4-amine 9b was endowed with good binding energy. Also, the obtained products were evaluated for their in vivo antiinflammatory activity as prostaglandin inhibitiors (% inhibition of edema and % inhibition of plasma PGE2 at the two dose levels were determined). The tested compounds exhibited significant anti-inflammatory activity and minor ulcerogenic effects, when compared to the reference standard indomethacin, with product 9b being of particular interest.

Activation-induced apoptosis in peripheral blood mononuclear cells during hepatosplenic Schistosoma mansoni infections.

It is well established that programmed cell death (apoptosis) is an important regulator of host responses during infection with a variety of intra- and extra-cellular pathogens. The present work aimed at assessment of in vitro spontaneous and phytohemagglutinin (PHA)-induced apoptosis in mononuclear cells isolated from patients with hepatosplenic form of S. mansoni infections. Cell death data were correlated to the degree of lymphoproliferative responses to PHA as well as to the serum anti-schistosomal antibody titers. A markedly significant increase in PHA-induced apoptosis in lymphocytes isolated from S. mansoni-infected patients was seen when compared to the corresponding healthy controls. However, a slight difference was recorded between the two studied groups regarding the spontaneous apoptosis. This was accompanied with a significant impairment of in vitro PHA-induced lymphoproliferation of T cells from S. mansoni patients. Data of the present study supports the hypothesis that activation-induced cell death (AICD) is a potentially contributing factor in T helper (Th) cell regulation during chronic stages of schistosomiasis, which represents a critically determinant factor in the host-parasite interaction and might influence the destiny of parasitic infections either towards establishment of chronic infection or towards host death.

A longifurcate distome cercaria from Bulinus truncatus snails in the Jordan Valley, Jordan.

Bulinus truncatus snails collected from water bodies of the South Shuna region, north of the Dead Sea, were found infected with a pharyngeal longifurcate distome cercaria. This new form of cercaria is named Cercaria bulini I. It has three pairs of penetration glands, 12 pairs of flame cells, and lacks the intestinal cecae. This cercaria is an active swimmer and develops within an elongated sporocyst. Other details on the morphology, behavior, and development of C. bulini I are presented.

Development, growth, and migration of Philophthalmus gralli (Trematoda) from Jordan in the eyes of chicks.

The growth of Philophthalmus gralli from Jordan was studied experimentally by inoculating 10 excysted metacercariae around the right eye of 47 day-old chicks. The growth rate was slow in the first three days during which flukes did not exceed 0.30 mm long. Then growth became rapid reaching 2.70 mm long on day 24. This was followed by a low growth rate during which the flukes grew from 2.70 mm to 2.90 mm on day 40. The flukes started to appear in the left eye on day 12 post-inoculation of metacercariae in the right eye. The recovery of flukes in the left eye increased from 5% on day 12 to 30% on day 32. The development of P. gralli from Jordan was the same as of other species of Philophthalmus. However, a sixth stage, post-maturation stage, is suggested in addition to the 5 developmental stages of Philophthalmus. The ratio of the transverse diameter of the ovary to that of testes in the post-maturation stage was 1:1.1-1:1.2.

Serodiagnosis of Toxoplasma gondii in habitually aborting women and other adults from North Jordan.

The prevalence of anti-Toxoplasma gondii antibodies in serum samples of 55 habitually aborting women, 46 women with normal pregnancies, 92 outpatient adults, and 150 University students from North Jordan was studied using the enzyme linked immunosorbent assay (ELISA). Sera from the habitually aborting group were also tested by the indirect immunofluorescent (IIF) test. No significant difference was found between the overall prevalence rates in University students, outpatient adults and women with normal pregnancies (25.3%, 22.8% and 26.1% respectively). The prevalence in habitually aborting women exceeded two times that in women with normal pregnancies or in outpatient females (58.2%, 26.1% and 25.0% respectively), and was approximately three times that in female University students (18.3%). The greatest difference in the prevalence rate between habitually aborting women and those with normal pregnancies or outpatient females was found in groups having the highest antibody level (greater than or equal to 100% of standard positive controls). A positive correlation between the results of the ELISA and those of the IIF test occurred at titres of greater than or equal to 1:40 of the latter test in habitually aborting women.