No abstract

In recent years, the demand for effective and low-toxic stimulators of rhizogenesis, which are used in microclonal propagation of plants, has been increasing in Ukraine. One of the promising directions in the search for effective compounds is molecular modeling based on known natural and synthetic compounds. The development of new highly effective and low-toxic biologically active compounds is largely based on derivatives of nitrogen-containing heterocycles, and quinoline occupies a significant place among them. Modern methods of chemometric analysis make it possible to find certain regularities in the "chemical structure – biological activity" and to select the most promising compounds for experimental research. The values of lipophilicity log P for neutral forms and the value of the distribution coefficient log D at pH = 7 were obtained by quantum chemical calculation. The values of log P and log D of the studied compounds are in the most favourable interval for overcoming the biological membranes of the cells of the root system, depending on the pH of the environment. According to Lipinski’s "rule of five", all studied compounds can show high biological activity. The toxicity of compounds of 2-((6-R-quinolin-4-yl)thio)acetic acid derivatives was evaluated by computer programs and experimentally. Among the derivatives of 2-((6-R-quinolin-4-yl)thio)acetic acid, the most toxic compounds were those that did not have alkoxy substituents in the 6th position of the quinoline ring. Sodium salts are more toxic than the corresponding acids. This is due to an increase in the bioavailability of ionized compounds. Derivatives of 2-((6-R-quinolin-4-yl)thio)acetic acid (sodium salt of 2-((quinolin-4-yl)thio)acetic acid (QAC-5) showed the greatest toxic effect on the model of the study of progressive sperm motility) and 2-((quinolin-4-yl)thio)acetic acid (QAC-1), which will reduce this indicator by 15–20% compared to intact. The toxicity assessment of the studied compounds made it possible to determine a number of factors of the structure of molecules which affect the level of toxic action of 2-((6-R-quinolin-4-yl)thio)acetic acid derivatives and the directions of creation of non-toxic growth stimulants in this series. The impact on rhizogenesis during microclonal reproduction in vitro in explants Paulownia clone 112 and further adaptation of microplants in vivo hybrid molecules of quinoline and acetic acid, which are analogues of known growth stimulants, was studied. A number of factors influencing the level of influence on rhizogenesis of the action of derivatives of 2-((6-R-quinolin-4- yl)thio)acetic acid and directions of creation of highly active substances in this series was defined. The studied compounds showed a high stimulating effect on rhizogenesis in vitro in Paulownia explants. It was established that the sodium salt of 2-((quinolin-4-yl)thio)acetic acid was the greatest stimulator of rhizogenesis compared to the corresponding original acid. The presence of alkoxy groups in the 6th position and methyl in the 2nd position of the quinoline ring of 2-((6-R-quinolin-4-yl)thio)acetic acid reduced the activity of the compounds. The selection of new effective, low-toxic, less expensive substances was carried out for further testing as potential stimulators of rhizogenesis for microclonal propagation of plants.

In recent years, much attention has been paid specifically to the modification of natural compounds in order to obtain more effective biologically active substances, which are endowed with the necessary complex of properties. Nitrogen-containing quinoline derivatives (quinoline, Q) is one of the promising directions for the search for biologically active substances with antimalarial action based on quinoline alkaloids (quinine and its analogs). They are also endowed with antimicrobial activity and occupy an important place in the modern arsenal of antibacterial chemotherapeutic agents. Quinoline preparations act mainly on the gram-negative flora, and also have antiprotozoal action (dysentery amoeba, giardia, trichomonas, etc.).The data on the biological activity of quinoline halogens are analyzed. They have been found to be promising biologically active substances with various types of biological action, such as: antimalarial, antibacterial, antioxidant and other signs of biological action. There are also compounds with anti-cancer and immunomodulatory properties, promising structures for the treatment of herpes virus. The inhibition of antimicrobial activity of gram-positive and gramnegative microorganisms was established. Among quinoline derivatives, substances have been found that demonstrate not only bacteriostatic and fungistatic activity but also analgesic. Quinoline derivatives with halogen atoms demonstrate the considerable potential of antimalarial, antimicrobial and antiparasitic drugs.The introduction of chlorine or bromine atoms into the structure of the 8-hydroxyquinoline molecule led to a significant increase in their biodiversity, and fluorine -for quinolones-4generally created the preconditions for the development of a number of synthetic antibiotics. A number of antimicrobials have been developed based on quinolone derivatives, in particular synthetic antibiotics -fluoroquinolones.In addition, quinoline derivatives are used as pesticides, veterinary drugs, dyes, chemical reagents and others.