Assessment of Acute Toxicity of Quinazoline Derivative 3-[2-oxo-2-(4-Phenylpiperazine-1-yl)Ethyl]quinazoline-4(3h)-oh Active against Opportunistic Microorganisms

N. M. Gabitova, A. A. Tsibizova, A. Ozerov, M. Samotrueva
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Abstract

The study is devoted to the study of acute toxicity of a new quinazoline compound — 3-[2-Oxo-2-(4-phenylpiperazine-1-yl)ethyl]quinazoline-4(3H)-one (VMA-10-21), promising as an antimicrobial agent active against opportunistic microorganisms. Purpose. Assessment of acute toxicity of the quinazoline derivative 3-[2-oxo-2-(4-phenylpiperazine-1yl)ethyl] quinazoline-4(3h)-oh, exhibiting antimicrobial activity. Material and methods. All experiments were carried out on non-linear mature female rats with a body weight of 180–190 g. Female individuals were in the diestrus stage. The rats were divided into groups (n=6) by a random sample, there were 4 individuals in each group and were kept in cages for a week before the experiment, getting used to laboratory conditions: animals receiving intragastric equiobjection of distilled water (control); experimental animals treated with the compound VMA-10-21 at doses of 1000, 2000; 5000 mg/kg (the doses were selected based on the fact that the study of the toxicity of pyrimidine derivatives with a similar chemical structure showed their relative safety and the absence of lethality from a dose of 500 mg/kg). Results. Assessment of acute toxicity of the quinazoline derivative 3-[2-oxo-2-(4-phenylpiperazine-1yl)ethyl]quinazoline-4(3h)-oh with intragastric administration showed that this compound belongs to class 5 toxicity and is low-toxic according to. Under these conditions, and for LD₅₀, the maximum dose is 5000 mg/kg. However, despite the results obtained, when this compound was administered at a dose of 5000 mg/kg, changes in hemoglobin, the number of leukocytes and platelets, as well as total protein were observed, which may indicate the possible development of pathological changes in the hematopoietic and hepatobiliary systems. Conclusion. Thus, the quinazoline derivative 3-[2-oxo-2-(4-phenylpiperazine-1yl)ethyl]quinazoline-4(3h)-oh with intragastric administration is low-toxic and belongs to the 5th class of toxicity, and therefore the maximum dose is 5000 mg/kg for LD₅₀. However, given the fact that there are changes in hematological and biochemical parameters, this compound needs to be studied in detail under the conditions of course effects on the body of animals.
喹唑啉衍生物3-[2-氧-2-(4-苯基哌嗪-1-酰基)乙基]喹唑啉-4(3h)-oh对条件微生物的急性毒性评价
本研究致力于研究一种新的喹唑啉化合物- 3-[2-氧-2-(4-苯基哌嗪-1-酰基)乙基]喹唑啉-4(3H)- 1 (VMA-10-21)的急性毒性,该化合物有望作为一种抗机会微生物的抗菌剂。目的。喹唑啉衍生物3-[2-氧-2-(4-苯基哌嗪-1基)乙基]喹唑啉-4(3h)-oh具有抗菌活性的急性毒性评价。材料和方法。所有实验均在体重180-190 g的非线性成熟雌性大鼠身上进行。雌性个体处于绝育期。大鼠随机分为6组,每组4只,实验前在笼中饲养1周,以适应实验条件:对照组灌胃等量蒸馏水;用化合物VMA-10-21按1000、2000剂量处理实验动物;5000 mg/kg(选择剂量的依据是,对具有类似化学结构的嘧啶衍生物的毒性研究表明,它们相对安全,500 mg/kg的剂量没有致命性)。结果。对喹唑啉衍生物3-[2-氧-2-(4-苯基哌嗪-1基)乙基]喹唑啉-4(3h)-oh经胃给药的急性毒性评价表明,该化合物属于5级毒性,根据在这些条件下,对于LD₅0,最大剂量为5000mg /kg。然而,尽管获得了这些结果,当该化合物以5000 mg/kg的剂量给药时,观察到血红蛋白、白细胞和血小板数量以及总蛋白的变化,这可能表明造血和肝胆系统可能发生病理改变。结论。因此,喹唑啉衍生物3-[2-氧-2-(4-苯基哌嗪-1基)乙基]喹唑啉-4(3h)-oh经胃给药是低毒的,属于第5类毒性,因此LD₅0的最大剂量为5000mg /kg。但由于存在血液生化参数的变化,该化合物对动物机体的作用还需要在一定条件下进行详细的研究。
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