Search

Introduction. The study of the effects of the long-term effect of the active substances of pesticides on the body of warm-blooded animals is an obligatory stage of their comprehensive toxicological and hygienic assessment. The aim of the study was to establish the levels of inactive doses of the effects of the long-term (NOEL) action of a compound of the oxatiine class. Materials and methods. In accordance with the planned purpose of the study in the biological testing laboratory of the Federal Scientific Center of Hygiene named after F.F. Erisman of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing еxperiments were conducted to establish the parameters of acute oral toxicity, the presence of possible teratogenic and embryotoxic effects, and the effect on the reproductive function of a technical product of the oxatiin class (TPO) on the body of warm-blooded (rats). Previously, studies in this volume have not been conducted. Results. LD50 of the studied compound with a single oral administration to male rats is more than 4500 mg/kg of body weight. When studying the embryotoxic effect, the inactive dose for the maternal organism and offspring is set at the level of – 1/52 LD50; the inactive dose for the teratogenic effect for the maternal organism is 1/52 LD50, offspring – 1/27 LD50. As a result of studying the effect of the oxatiine derivative on the indicators of reproductive function, the inactive dose for maternal, paternal organisms, and offspring, is 1/313 LD50. Limitations. In our study to establish the levels of inactive doses of the long-term effects of toxicity of a technical product derived from oxatiines, there are no data on the results of the mutagenic effect of the studied compound on the body of warm-blooded (rats, mice). Conclusion. It has been established that according to the “Hygienic classification of pesticides and agrochemicals according to the degree of danger” (Methodological Recommendations of MP No. 1.2.0235-21* dated 02/15/2022), the studied chemical product belongs to the 4th hazard class for acute oral toxicity (LD50) and teratogenic effect (low-hazard compound; for embryotoxic effect and reproductive toxicity to the 3rd hazard class (moderately dangerous compound).

Introduction. The study of the remote effects (embryotoxicity, teratogenicity and reproductive toxicity) of new technical products on the mammalian body is the scientific basis for the safe use of pesticides. The purpose of the study is to study the effect of a new technical product of the benzoyl urea class on the development of remote effects in warm-blooded animals (rats). Material and methods. The evaluation of embryotoxic and teratogenic effects was carried out on laboratory animals (rats, males and females). Doses were studied: 0, 1/5000, 1/2500 and 1/1250 LD50. Each group of females consisted of 15 animals with a body weight of 230-240 g at the beginning of the study. The technical product was administered orally to female rats daily during 6-20 days of pregnancy. Fertilization of females with intact males was carried out in a ratio of 2 : 1. Reproductive toxicity was studied on two generations of rats (males; 10 individuals per group and females; 20 individuals per group) at doses of 0, 1/5000, 1/2500 and 1/624 LD50. Results. Embryotoxic and teratogenic effects were not detected, significant changes in reproductive toxicity were established at the maximum dose (for parents and offspring). Limitations. In study, there are no data on the study of organ tissues, nor have the processes of cell damage as a result of exposure to a new technical product derived from the benzoyl urea class been studied. Conclusion. The conducted studies have confirmed that the studied product of the benzoyl urea class belongs to low-risk compounds in terms of embryotoxicity and teratogenicity; moderately dangerous in terms of its effect on the reproductive function of warm-blooded (rats).

The development of multi-target-directed ligands (MTDLs) would provide effective therapy of neurodegenerative diseases (ND) with complex and nonclear pathogenesis. A promising method to create such potential drugs is combining neuroactive pharmacophoric groups acting on different biotargets involved in the pathogenesis of ND. We developed a synthetic algorithm for the conjugation of indole derivatives and methylene blue (MB), which are pharmacophoric ligands that act on the key stages of pathogenesis. We synthesized hybrid structures and performed a comprehensive screening for a specific set of biotargets participating in the pathogenesis of ND (i.e., cholinesterases, NMDA receptor, mitochondria, and microtubules assembly). The results of the screening study enabled us to find two lead compounds (4h and 4i) which effectively inhibited cholinesterases and bound to the AChE PAS, possessed antioxidant activity, and stimulated the assembly of microtubules. One of them (4i) exhibited activity as a ligand for the ifenprodil-specific site of the NMDA receptor. In addition, this lead compound was able to bypass the inhibition of complex I and prevent calcium-induced mitochondrial depolarization, suggesting a neuroprotective property that was confirmed using a cellular calcium overload model of neurodegeneration. Thus, these new MB-cycloalkaneindole conjugates constitute a promising class of compounds for the development of multitarget neuroprotective drugs which simultaneously act on several targets, thereby providing cognitive stimulating, neuroprotective, and disease-modifying effects.