ÓÄÊ 576.89
DOI 10.33861/2071-8020-2026-1-24-28
Original Empirical Research
Zubenko A. A., Fetisov L. N., Svyatogorova A. E., Yarovaya N. A., Bayramova V. N.
Abstract. Condensed diase heterocycles form the basis of many bioactive natural products and effective therapeutic drugs. Among them, phthalazines are recognized as outstanding structural leaders in medicinal chemistry due to their wide application in the pharmaceutical and agrochemical industries. Gaining access to such complex pharmaceutical agents with high chemical complexity through synthetically effective approaches remains an attractive goal in modern medicinal chemistry and drug development. The aim of the research was to synthesize and study the biological activity of new derivatives of phthalazine carboxylic acids. The key compound is dicarboxylic acid No. 1 (Table 1), which interacts with hydrazine hydrate to produce phthalazic acid A. The reaction of phthalazic acid A with phosphorus chloride produced dichloroproduct B, which under mild conditions reacts with the corresponding amines to form amides B. The reaction of amides with the corresponding nucleophiles during boiling in methyl cellulose produced 15 new compounds. The biological activity of new compounds was studied using methods used in experimental chemotherapy. It has been found that most compounds have activity to one degree or another. A significant level of antibacterial activity was found in diacid No. 1 against Staphylococcus aureus, equal to the activity level of the comparison drug furazolidone, as well as noticeable activity against Esherichia coli. It seems promising to synthesize analogues of this diacid with both donor and acceptor substituents in order to enhance activity. Compound No. 14 also showed significant antiprotozoal activity, equal to the activity level of the reference drug toltrazuril. Significant fungistatic activity is observed in compound No. 10 with a lipophilic substituent for both Penicillium italicum and Staphylococcus aureus. The introduction of lipophilic substituents may become a promising direction for modifying the structures of this series to enhance biological activity.
Keywords: phthalazine, phthalazine carboxylic acids, biological activity, antiprotozoal activity, fungistatic activity, antibacterial activity.
References:
1-18. Vide supra.
Author affiliation:
Zubenko Aleksandr A., D.Sc. in Biology, Chief Scientific Researcher of the creative team for the chemical synthesis of new medicinal compounds of the Federal Rostov Agricultural Research Centre; 0, Rostov hghw., Novocherkassk, Rostov region, 346421; phone: 8-928-6049743; e-mail: alexsandrzubenko@yandex.ru.
Fetisov Leonid N., Ph.D. in Veterinary Medicine, Leading Scientific Researcher of the creative team for the chemical synthesis of new medicinal compounds of the Federal Rostov Agricultural Research Centre; 0, Rostov hghw., Novocherkassk, Rostov region, 346421; phone: 8-908-1978224; e-mail: fetisoff.leonid2018@yandex.ru.
Yarovaya Natalia A., Laboratory Researcher of the creative team for the chemical synthesis of new medicinal compounds of the Federal Rostov Agricultural Research Centre; 0, Rostov hghw., Novocherkassk, Rostov region, 346421; phone: 8-999-2340481; e-mail: tkhim.sintez@yandex.ru.
Bayramova Violetta N., Laboratory Researcher of the creative team for the chemical synthesis of new medicinal compounds of the Federal Rostov Agricultural Research Centre; 0, Rostov hghw., Novocherkassk, Rostov region, 346421; phone: 8-938-4043648; e-mail: tkhim.sintez@yandex.ru.
Responsible for correspondence with the editorial board: Svyatogorova Aleksandra E., Ph.D. in Agriculture, Leading Scientific Researcher of the creative team for the chemical synthesis of new medicinal compounds of the Federal Rostov Agricultural Research Centre; 0, Rostov hghw., Novocherkassk, Rostov region, 346421; phone: 8-988-9525755; e-mail: sviatogorova.a@yandex.ru.
Authors’ Contribution: the manuscript was written with the input of all authors. All authors approved the final version of the manuscript.
Conflict of Interest Statement: the authors declare no conflict of interest.
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