New antimicrobial 9-[p-heterocyclo-substituted anilino]-tetrahydroacridines

The chemistry of tetrahydroacridines is of continuous interest, as they are associated with pharmacological activities[1-9]. Some members of this class of compounds are used as memory-enhancing agents for treating Alzheimer disease [1, 2] acetylcholine esterase inhibitors[3-5], DNA-binding agents[6], antimicrobial agents[7] and as amoebicides[7-9]. The present work deals with the synthesis of a new series of 9-[p-[4-aryl- 3-cyano-2-iminopyridin-6-yl] anilino]-1, 2, 3, 4-tetrahydroacridines [3] and their 2-oxo-[or thioxo]-pyridinylanilino derivatives 4 and 5, besides other related products 7-12 to be evaluated against bacteria and fungi. Synthesis was achieved by allowing 9-chloro-1, 2, 3, 4-tetrahydroacridine [1][10] to react with p-aminoacetophenone to give the 9-[p-acetylanilino] derivative 2. The one pot reaction of 2 with malononitrile, ammonium acetate and the appropriate aromatic aldehyde afforded the corresponding 9-[p-[4-aryl-3-cyano-2-iminopyridin-6-yl]-anilino]-1, 2, 3, 4-tetrahydroacridines [3a-e], respectively [Route a]. Similarly, reaction of 2 with ethyl cyanoacetate, ammonium acetate and the appropriate aromatic aldehyde in n-butanol afforded the corresponding 9-[p-[4-aryl-3-cyano-2[1H]-oxo-pyridin-6-yl] anilino]-1, 2, 3, 4-tetrahydroacridines [4a-d], respectively. On the other hand, the reaction of an ethanolic mixture of 2 with substituted arylmethylene cyanothioacetanilides [5][11, 12] in the presence of ammonium acetate gave the corresponding 3-cyano-4-arylpyridin-2[1H]-thiones [6a-d], respectively [Route a]. Also reaction of 1 with ethyl-p-aminobenzoate gave the corresponding ethyl-p-[1, 2, 3, 4-tetra-hydroacridin-9-yl] aminobenzoate [7] which upon reaction with hydrazine hydrate afforded the corresponding acid hydrazide 8. [Route b]. In addition, acetylation of 2 was accomplished by heating it with ethyl acetate in the presence of sodium metal to give p-[[1, 2, 3, 4-tetrahydroacridin-9-yl]amino]acetylacetophenone [9]. Bromination of 2 afforded 9-[p-bromo-acetyl anilino]-1, 2, 3, 4-tetrahydroacridine [10] which upon reaction with thiourea gave the corresponding 9-[p-[2-aminothiazol-4-yl]aniline-1, 2, 3, 4-tetrahydroacridine [11] was hydrobromide salt, while reaction of 10 with malononitrile afforded p-[1, 2, 3, 4-tetrahydroacridin-9-yl]amino-benzoylmethyl malononitrile [12] [Route c]

Nutritional outcome of appropriate feeding during and after acute diarrhoea in children

A sample of 120 children with acute diarrhoea was divided into two equal study groups. There was no difference between groups in pre-intervention and post-intervention findings during the acute phase of diarrhoea. Upon discharge, Group A patients were supplied weekly with sufficient milk formula and cereal together with adequate nutritional advice while Group B patients were supplied with food or nutritional advice only if requested by the mothers. Forty nine patients from each group were followed each week for four weeks. Group B infants showed a higher incidence of recurrent diarrhoeal attacks and a significantly longer duration of recurrent diarrhoea than Group A infants. Moreover, Group A infants scored a significantly higher weight increment than Group B ones after four weeks of follow up

Histological and histochemical changes of the skin with aging

This study comprised skin biopsies from the upper back of 30 healthy males at different ages. They were divided into 3 groups of 10 males each, group I aged [20 - 40 years], group II aged [40 - 60 years] and group III aged over 60 years. The results of the present study showed marked histological and histochemical skin changes occurring with aging. The epidermis was reduced in thickness with flattening of the dermoepidermal junction with age. The thickeness of the epidermis was 67. 5 microm to 189 microm in the first group, 54 microm to 108 microm in the second group, 40. 5 microm to 81 microm in the third group. The basal cell layers of the epidermis showed areas of heterogenicity with variations in the shape, size and staining characters of their cells. The dermis of old subjects showed elastosis with more randomness in the arrangement of the elastic fibres. An overall decrease in the collagenous fibre content of the dermis was also demonstrated with aging. Both alkaline phosphatase and succinic dehydrogenase enzyme activity decreased with aging

Effect of the voltaren on the structure of male Albino rat liver

The present work dealt with the histological and histochemical changes in adult and senile rat's liver following the injection of a daily therapeutic dose of Voltaren [Ciba-Geigy] for three weeks. The main structural changes observed in the liver, in response to Voltaren administration, were the cytoplasmic vacuolation of most of hepatocytes. This effect gradually increased as the hepatocytes were traced peripherally within a hepatic lobule, so the peripherally situated cells were the most vacuolated ones. The vacuolations affected the hepatocytes of the adult rats more than those of the senile ones. The vacuoles were neither lipid nor glycogen in nature but were most probably due to water accumulation. Voltaren administration led to the accumulation of glycogen granules in the centrilobular hepatocytes of adult and senile rats. Only in senile rats an increase in the thickness of the collagenous fibers was observed in the connective tissue capsule and the connective tissue surrounding the central veins and the portal tracts. Voltaren administration to adult and senile rats resulted in a marked increase in the alkaline phosphatase activity of the cytoplasm and nuclei of most of hepatocytes. The drug also increased the acid phosphatase activity in the cytoplasm of the hepatocytes in the adult and senile animal groups

Histological and histochemical changes in the testis of Albino rat following zinc deficient diet

The present study showed that severe zinc deficiency [one part per million = 1- PPM] led to disorganization of the germinal epithelium which was accompanied by severe reduction in the germinal layers to the extent that some tubules were lined only by two layers of cells. The contents of D.N.A. and R.N.A. decreased in the spermatogenic cells and in Leydig cells while fat was accumulated in these cells. The activity of succinic dehydrogenase was increased in proportion to the magnitude of zinc deficiency

Bencard skin test in chronic urticaria

Bencard pitch skin tests with different allergens were performed on 127 patients with chronic urticaria. 100 [78.7%] patients were reactive while 27 [21.3%] patients were non reactive. No significant correlation was found between prick skin test results and either the age or the sex of the patients. Highest percentages of positivity were found with inhalant allergens e.g. house dust [44/127 i.e. 34.6%]; house dust mite [30/127 i.e. 23.6%] and feathers [26/124 i.e. 20.4%]. Atopy however, does not seem to play an important role in chronic urticaria. Prick tests with food allergens showed positive reactions in 15.7% [20/127] of patients. Most of the patients with penicillin allergy were recommended to be on a diet free from milk and milk products. In 50% this was successful. The value of these findings is discussed. Desensitization was performed for 47 patients. 21 [44.7%] only reported improvement. The frequent recurrence and the life long treatment limit its value. Desensitization is thus recommended in the routine treatment of chronic urticaria