الفهرس 
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Abstract
In order to reduce protein deficiency in nutrition or to terminate it, thorough and significant research is being carried out throughout the world. One of the most obvious ways to achieve this objective is the use of additives to nutrients and feed which improve the utilization of the nutrients. In animal husbandry, these additives result in higher body-weight.
Pyrimidine derivatives (quinazolinones) have been subjected to a detailed investigation from the aspect of their body weight increasing effect. These compounds are rather widespread in nucleic acids of DNA and RNA and some vitamins.
This work illustrates that the benzoxazinone 1 was allowed to react with hydrazine hydrate in EtOH at as boiling point in presence of drops of piperidine to give 3-amino-2-phenylquinazolin-4(3H)-one 2. When the same reaction was conducted in absence of piperidine, the corresponding acyclic product 2-benzamido-benzohydrazide 3 was isolated. [cf. Scheme I].
Schiff’s base was prepared by the condensation of 3-amino-2-phenylquinazolin-4(3H)-one 2 with 4-oxo-4H-chromene-3-carbaldehyde 4 in presence of MeOH/ AcOH to afford 3-(((4-oxo-4H-chromen-3-yl)methylene)amino)-2-phenylquinazolin-4(3H)-one 5. Whereas, 2-benzamidobenzo-hydrazide 3 was condensed with the same aldehyde 4 in EtOH to yield Schiff ‘s base compound (N-{2-[2-(4-oxo-4H-chromen-3-yl) acetyl] phenyl} benzamide) 6 [cf. Scheme I].
Scheme I
Pharmacological Activities:
Calculation of Acute Toxicity (LD50):
The LD50 value was calculated as the geometric mean of the highest non-lethal and the lowest lethal doses mathematically according to Kerber method (Pershin) using the following formula:
LD50 = LD100 - ∑ (z x d) / m
where z is the half of sum of animal quantity died from two next doses; d is the interval between two next doses and m is the number of animals/ group. LD100 is the largest dose which kills all animals.
Biological Activities:
The present study was carried out to investigate the changes in body weight, some heamatological and biochemical parameters in blood of growing rabbits during the oral administration and after withdrawal of pyrimidine derivatives (quinazolinone).
Fifty healthy New Zealand White rabbits (45±6 day old) were classified into five groups, 10 rabbits per group, control group and 4 treated groups.
group I: Control, rabbits were oral administrated with similar volume of distilled water and Tween 80; (1%).
group II: Q1 rabbits were oral administrated with compound 3 (2-benzamidobenzohydrazide) [LD50 (70 mg/kg b.w.)] suspended in distilled water and tween 80; 1%.
group III: Q2 rabbits were oral administrated with compound 2 (3-amino-2-phenylquinazolin-4(3H)-one) [LD50 (80 mg/kg b.w.)] suspended in distilled water and tween 80; 1%.
group IV: C1 rabbits were oral administrated with compound 6 N-(2-(2-((4-oxo-4H-chromen-3-yl) methylene) hydrazine-1-carbonyl)-phenyl)benzamide [LD50 (200 mg/kg b.w)] suspended in distilled water and tween 80; 1%.
group V: C2 rabbits were oral administrated with compound 5 3-(((4-oxo-4H-chromen-3-yl)methylene)amino)-2-phenylquinazolin-4(3H)-one [LD50 (250 mg/kg b.w)] suspended in distilled water and tween 80; 1%.
Rabbits fed rabbit pellets ad libitum and were weighed every two weeks. Blood samples were collected (every 2 weeks) from the cardiac puncture of rabbit for a period two month (one month during treatment and other month after withdrawal) in two vacutainer tubes; one contains lithium heparin for analysis of hematological parameters [hemoglobin concentration, red blood cell count, white blood cell count and thrombocyte count then the separated plasma for determination concentration of glucose] and other tubes with no anticoagulant. Serum sample were used to determine total protein, albumin, globulin, (A/G) ratio, total cholesterol, triglycerides, high-density lipoproteins cholesterol, low-density lipoproteins cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine.
The results showed increase in percentage of weight gain during oral administration and after withdrawal of pyrimidine derivatives and their corresponding acyclic products of treated groups (Q1, Q2, C1 and C2) by (85.57%, 95.52%, 82.09% and 87.16%), respectively than control one by (51.60%).
The clinical heamatological and biochemical analysis of blood showed that:
1- During administration period:
There were a significant (P≤0.05) increase in hemoglobin concentration (HGB), red blood cell count (RBCs), serum total protein, A/G ratio, total cholesterol, triglycerides, HDL-c, LDL-c, VLDL-c levels, but the plasma glucose and globulin levels showed a significant (P≤0.05) decrease during administration.
2- After withdrawal period:
There was a significant (P≤0.05) increase in concentration of HGB, RBCs, plasma glucose, serum total protein, globulin and HDL-c but, the serum A/G ratio, total cholesterol, triglycerides, LDL-c and VLDL-c levels showed a significant (P≤0.05) decrease of treated groups when compared to control one after withdrawal period.
While, there were non-significant changes in the mean values of WBCs, PLT, albumin, ALT, AST, urea and creatinine concentrations during both the oral administration of pyrimidine derivatives and after withdrawal period of all experimental rabbits.