The synthesis of spiro[indole-3,1’-pyrrolo[3,4 -c]pyrrole]- 2,4’,6’-trione derivatives, the study of their antimicrobial activity and the molecular docking on staphylococcal dehydrosqualene synthase
Journal Title: Вісник фармації - Year 2018, Vol 94, Issue 2
Abstract
Aim. To synthesize the series of new spiro[indole-3,1’-pyrrolo[3,4-c]pyrrole]-2,4’,6’-trione derivatives, study their physicochemical characteristics, antibacterial activity and precision of the molecular docking on the model of staphylococcal dehydrosqualene synthase.Materials and methods. The methods of organic synthesis, instrumental methods for analysis of organic compounds, as well as the molecular docking method in silico and agar diffusion method in vitro were used. Results and discussion. To synthesize new bis-derivatives of 3’a, 6’a-dihydro-3’H-spiro[indole-3,1’-pyrrolo[3,4-c]pyrrole]-2,4’,6’-triones the three-component reaction of 1,6-maleimidamidohexane with L-amino acids and isatin was studied. New bis-spiro derivatives were isolated with a double excess of the corresponding isatin and L-amino acids. With the equimolar ratio of three reagents 6-N-maleimidohexyl derivatives spiro[indole-3,1’-pyrrolo[3,4-c]pyrrole]-2,4’,6’-triones were isolated with the yields of 30-90 %. To prove their reactivity two symmetrical bis-spirooxindoles were counter-synthesized by condensation of two 6-N-maleimidohexyl spiro-2-oxindole derivatives with isatin, L-phenylalanine or sarcosine with the yields of 35 and 38 %. In the microbiological screening it was found that some compounds revealed the activity against S. aureus at the level of cefalexin and against C. albicans fungi relative to fluconazole. The docking in silico identified a high ability of the compounds studied to interact with at least six key amino acid residues – Arg45, Asp48, Asp52, Gln165, Asn168 and Asp172 of the active center of S. aureus dehydrosqualene synthase (CrtM).Conclusions. It has been found that the one-pot three-component reaction of isatin, L-amino acids and 1,6-maleimidohexane as a function of the mole ratio of the reagents leads to both bis-derivatives of spiro[indole-3,1’-pyrrolo[3,4-c]pyrrole]-2,4’,6’-trione, and to the corresponding asymmetric 6-N-maleimidohexyl derivatives. The substances synthesized have predominantly shown the activity in relation to gram-positive bacteria and yeast-like fungi. For the first time it has been demonstrated by the molecular docking method that the compounds studied forming a complex with a high docking score are potential inhibitors of staphylococci CrtM.
Authors and Affiliations
R. G. Redkin, K. V. Hlebova
Keywords
Related Articles
- EP ID EP666391
- DOI 10.24959/nphj.18.2210
- Views 90
- Downloads 0
Изучение биофармацевтических и адгезионных характеристик стоматологического геля
Значительная распространенность стоматологических патологий среди различных возрастных групп населения Украины диктует необходимость поиска новых эффективных ле-карственных средств, применяемых в терапии заболеваний поло...
Соціальна значущість проведення фармакогенетичного тестування в Україні на прикладі гена CYP2B6, що бере участь у метаболізмі нікотину
Вивчення проведення фармакогенетичного тестування в Україні на прикладі гена CYP2B6, який бере участь у метаболізмі нікотину, є актуальною і соціально значущою проблемою. Мета. Визначення потенційної вибірки серед жител...
The study of the chemical composition of the components of the motherwort herb
Aim. To study phytochemically the components of the motherwort (Leonurus cardiaca) herb and determine which overground organs contain the greatest number of active substances and affect the quality of medicines based on...
Фармакогностическое изучение надземной массы Prangos ferulacea lindl. в стадии начала вегетации
Цель работы – изучить кумариновый состав засоленной травы Prangos ferulacea, заготовленной в стадии вегетации, и сравнить его с кумариновым составом свежезаготовленного сырья.Материалы и методы. Анализ проведен на Agilen...
Экспериментальное исследование крема с наночастицами диоксида церия на модели фотодинамической травмы у морских свинок
Цель работы – изучение фотопротекторной активности крема с наночастицами диоксида церия (НДЦ) на модели фотодинамической травмы у морских свинок.Материалы и методы. НДЦ синтезированы в ООО «НаноМедТех», крем с НДЦ разраб...