THE SYNTHESIS OF 1-OXA-9-AZASPIRO[5.5]UNDECANE DERIVATIVES AND OPTIMIZATION OF ANTITUBERCULOSIS ACTIVITY THEREOF

Authors

  • Kristina Yu. Komarova Russian Technological University, Lomonosov Institute of Fine Chemical Technologies, 78 Vernadsky Ave., Moscow 119571
  • Alexey Yu. Lukin Russian Technological University, Lomonosov Institute of Fine Chemical Technologies, 78 Vernadsky Ave., Moscow 119571. Saint Petersburg State Research Institute of Phthisiopulmonology, the Ministry of Health of the Russian Federation, 2-4 Ligovsky Ave., Saint Petersburg 191036
  • Lyubov V. Vinogradova Russian Technological University, Lomonosov Institute of Fine Chemical Technologies, 78 Vernadsky Ave., Moscow 119571
  • Maxim Е. Zhuravlev Russian Technological University, Lomonosov Institute of Fine Chemical Technologies, 78 Vernadsky Ave., Moscow 119571
  • Marine Z. Dogonadze Saint Petersburg State Research Institute of Phthisiopulmonology, the Ministry of Health of the Russian Federation, 2-4 Ligovsky Ave., Saint Petersburg 191036
  • Tatiana I. Vinogradova Saint Petersburg State Research Institute of Phthisiopulmonology, the Ministry of Health of the Russian Federation, 2-4 Ligovsky Ave., Saint Petersburg 191036
  • Maxim А. Gureev Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., Saint Petersburg 194064
  • Mikhail V. Chudinov Russian Technological University, Lomonosov Institute of Fine Chemical Technologies, 78 Vernadsky Ave., Moscow 119571
  • Dmitry V. Dar'in Saint Petersburg State Research Institute of Phthisiopulmonology, the Ministry of Health of the Russian Federation, 2-4 Ligovsky Ave., Saint Petersburg 191036. Saint Petersburg State University, 7/9 University Embankment, Saint Petersburg 198504

Keywords:

1-oxa-9-azaspiro[5.5]undecane, spirocyclic compounds, antituberculosis activity, MmpL3 protein, Prins cyclization

Abstract

The aim of this work was to synthesize and study the antituberculosis activity of spirocyclic inhibitors of the MmpL3 protein of M. tuberculosis containing the 1-oxa-9-azaspiro[5.5]undecane scaffold. Optimization of the initial structure was performed with consideration of the results of molecular docking. The resulting compounds, characterized by the chemical diversity of the peripheral fragment, showed high activity against the antibiotic-sensitive strain H37Rv and some multiresistant strains of M. tuberculosis, exceeding the activity of the comparator drug.

Author Biography

Dmitry V. Dar'in, Saint Petersburg State Research Institute of Phthisiopulmonology, the Ministry of Health of the Russian Federation, 2-4 Ligovsky Ave., Saint Petersburg 191036. Saint Petersburg State University, 7/9 University Embankment, Saint Petersburg 198504

Доцент кафедры органической химии Института химии СПбГУ

Downloads

Additional Files

Published

2024-08-01

Issue

Vol. 60 No. 5/6 (2024)

Section

Original Papers