Amino acid and peptide derivatives as anti-allergic and anti-inflammatory agents

It was proved that current anti-allergic drugs comprise piperazine and acrylic acid segments. These compounds were structurally designed as 5-lipoxygenase inhibitors depending on two action mechanisms of the ready drugs used to treat allergy e.g.[Oxatomide], which contains piperzine moiety, its anti-allergic effects possess antagonist activities against chemical mediators such as histamine, serotonine and leukotrienes [which cause allergy]. Also, [Tranilast], which contains acrylic acid segment; its activity depends on inhibition of mediator release. In harmony with these findings new structures having anti-allergic properties are proposed in this manuscript. New products, [5a-u] with expected better biological activities and decreased side effects were synthesized by the addition of an amino acid conjugate of cinnamic acid to a piperazine segment. Their anti-allergic and anti-inflammatory activities were evaluated. Most of them show promising activities

Gradual monitoring the antioxidant and antineoplastic effects of soybean and Nigella sativa during hepatocarcinogenesis

Objectives: Trials are continually undertaken to investigate the antioxidant and the antitumor activities of a long list of promising natural and synthetic compounds. This study was designed to investigate, in a stepwise manner, the antioxidant and antihepatocarcinogenic effects of soybean [SB] and Nigella sativa [NS] in rats endogenously producing dibutylnitrosamine [DBN]

Materials and Methods: To establish this goal, rats were randomly divided into four groups, each containing 48 animals. Group I [control], group II [dibutylamine [DBA]+NaNO3], group IH [DBA/NaNO3 + SB treated] and group IV [DBA/NaNO3 + NS treated]. Markers of oxidative stress [reduced glutathione [GSH] and nitric oxide [NO]] and the levels of HER-2/neu, bcl-2 and p53 proteins were investigated in rat's liver after 2, 4, 6, 8, 10 and 12 months

Results: The obtained data revealed an improvement in the status of oxidative stress represented as the compensation of GSH levels after 2 and 4 months and reduction of NO levels after 2 months in rats protected by SB or NS, respectively. The data revealed a significant improvement in the levels of HER-2/neu protein after 6 anti 4 months in rats protected with SB and NS, respectively. Also, both SB and NS offered and simultaneous improvement in the levels of bcl-2 after 2 months in both groups. Although, the level of p53 protein was ameliorated compared with the carcinogen control rats, it was maintained in a lower levels compared with the time matched points of the normal controls until 12 months

Conclusion: The data suggested that sustainable oral feeding of SB and NS antagonized the oxidant and neoplastic effects in DBA/NaNO3-induced hepatotocarcinogenesis and required a vaxiable time to completely normalize the level of the investigated parameters

Synthesis of some F-heterocyclic compounds of potential anticancer activity using 8-fluoro-1- benzosuberone as a synthon

8-fluoro-1-benzosuberone I condensed with aromatic aldehydes in the presence of potassium hydroxide to yield the arylmethylene derrivatives II, which condensed with phenylhydrazinc and thiourea to give the corresponding pyrazol and pyrimidine derivatives III and IV, respectively Compound IV reacted with chloroctic acid, alpha - bromopropionic acid or beta-bromopropionic acid to afford the thiazolopy-rimidine, methylthiazolopyrimia and thiazinopyrimidine derivatives V, VI and VII, respectively. Compound V condensed with aromatic aldehydes to afford the arylmethycine derivativcs VIII. Also, the pyrano and pyridino-fluorobenzosubcronc derivatives IX and X were synthesized. The obtained products were preliminarily tested as anticancer agents and it was found that the products IIa, IIb, IXa, IXb and X showed promising activity against non-small cell lung cancer

Oncogenic effect of some environmental pollutants and some possible protective agents

Objective: to study the effects of some environmental pollutants [lead, nitrate, noise stress and tobacco smoke] as well as a chemical substance [estrogenic oral contraceptive pills] on the incidence of malignant transformation among offspring rats through transplacental transfer from mother to fetus. The protective effect of Nigella sativa and vitamin A against the possible cellular transformation in the offspring rats was also studied

Subjects and Methods: five groups of female Sprague-Dawley rats [30 rats /group] were fed standard commercial diet. The first four groups were exposed to noise [100 decibel] and tobacco smoke for half an hour, three times weekly and received contraceptive pills daily. Group I received low doses of lead and nitrate, group I1 and group I11 were treated as group I but they were protected by adding to the diet crushed N. sativa to group I1 and vitamin A to group 111, while group IV received normal diet mixed with high doses of lead and nitrate. The fifth group served as untreated control. After three months no more contraceptive pills were added to the diet to prepare the female rats for meeting. After labour, mothers and their offspring were no more exposed to noise or tobacco smoke. The rats were sacrificed 45 days after labour, sera and tissues were saved for the biochemical and histopathological investigations

Setting: National Cancer Institute [NCI], Cairo University

Results: results showed an increase in the levels of mutant p53 protein, alpha-fetoprotein [AFP], ferritin and gamma glutamyl transferase [GGT] in the sera of both mothers and their offspring rats in the unprotected groups [I and IV] compared to the control group. On the other hand, the addition of N.sativa and vitamin A to the diet, led to a decrease in the levels of mutant p53, AFP and ferritin. Histopathological changes ranging from mild to severe dysplasia were found in both the mothers and their offspring rats in the two unprotected groups, while mild and moderate dysplasia were found to a less degree in the vitamin A protected group and disappeared from those fed N. sativa

Conclusion: the combined effects of the tested pollutants caused liver cells injury, ranging from mild to severe dysplasia, and raised the levels of serum mutant p53 protein, AFP, ferritin and GGT in both mothers and their offspring rats, which may lead on the long-term exposure to malignant transformation. On the other hand, N. sativa and vitamin A have a good protective effect which decreased both abnormal biochemical and histopathological changes

Synthesis and antimicrobial activity of some new Chiral Bridged macrocyclic pyridines

The utilization of 2,6-pyridinedicarboxylic acid [dipicolinic acid] in the synthesis of some chiral pridged bicyclic pyridine tripeptides is described. The antimicrobial activity of these natural cyclic peptides was tested

Synthesis and antimicrobial activity of 3,5-bis- [1-3,4-oxadiazol-5-yl] -, [1,3-thiazolo] hydrazony1-and [7H] s-Triazolo- [3,4-b] -1,3,4 Thiadiazinyl] pyridine derivatives

Different 3, 5-bis [oxadiazolyl] pyridine derivatives 3-5 have been obtained from 1 depending on the reaction condition. Reaction of 5 with amines or alkylhalides afforded the corresponding Mannich bases 6 or s-alkyl derivatives 7. The latter derivatived were treated with ammonium acetate to give 9 and with hydrazine hydrate affording bis bicyclic pyridine derivatives 10. Preliminary antimicrobial tests showed products 6e and 8 to possess higher activity when compared with oxytetracycline