Stereo- and regio-controlled synthesis of bioactive polycyclic molecules based on carbonyl compounds from the oxindole, naphthoquinone and androsterone series

Programme

 

Postdoctoral program

Strategic priority

V. Economic competitiveness and innovative technologies

Code
23.00208.5007.04/PD I
Duration
2023-2024
Institutions

Institute of Chemistry

Project manager
Abstract

The project is dedicated to obtaining enantiomerically pure compounds with biological properties, which provide greater activity and fewer side effects compared to a racemic or diastereomeric mixture. Target compounds will have a polycyclic structure, will be obtained on the basis of the modification of carbonyl substances and will have applicability in pharmacy and agriculture. The project will be carried out in 4 main stages and will include the synthesis and characterization of oxindole-based compounds, 2-hydroxyjuglone-based compounds, steroid-based compounds, as well as the formation and writing of the doctoral dissertation. In addition, in cooperation with the Rega Medical Research Institute (Leuven, Belgium), Aristotle University (Thessaloniki, Greece), Testimitsanu University of Medicine and Pharmacy (Moldova), Comrat State University (Moldova), the biological properties of the obtained compounds will be investigated. The project will be focused on conductive an exhaustive search of new and more effective drug candidates with the least cytotoxicity. To achieve this goal, two synthetic strategies will be applied. First, a library of analogues of substances similar to known natural and synthetic products will be created. Isatin, naphthoquinone and steroids will be used as the main elements to introduce molecular diversity. Secondly, a new library of mimetic derivatives will be obtained by introducing a new class of kernels for obtaining polycycles. Both strategies will use advanced synthetic approaches to create new bioactive chemical topologies that will bring economic and social benefits. At the final stage of the announced project, the conditions for obtaining the most promising compounds will be optimized and laboratory regulations will be developed to expand production.

Results, activities

The project is dedicated to obtaining compounds with biological properties in enantiomerically pure form, ensuring higher bioactivity and fewer side effects compared to racemic or diastereomeric mixtures. The synthesized compounds have a polycyclic structure and were obtained by modifying carbonyl compounds. In 2023, two planned stages were completed, involving the synthesis and characterization of compounds based on oxindole and compounds based on 2-hydroxyjuglone. The stages of 2023 focused on identifying new and more efficient candidates as alternatives to medications. To achieve this goal, two synthetic strategies were applied. Firstly, a library of analogues of substances similar to known natural and synthetic products was created. Isatin and naphthoquinone were used as basic elements to introduce molecular diversity. Secondly, a series of new derivatives were synthesized by introducing new nuclei to obtain polycyclic compounds. Advanced synthetic approaches were used for both strategies. In collaboration with the Rega Institute for Medical Research (Leuven, Belgium), Aristotle University (Thessaloniki, Greece), Ion Cuza University (Iași, Romania), and the Testimițeanu University of Medicine and Pharmacy (Moldova), biological testing of the obtained compounds was conducted.

Scientific report, 2023

Publications

Monograph
1. SUCMAN, N., MACAEV, F. Steroizi anabolizanți. Chisinau: CEP USM, 2023. 220 p. (în press)

Chapter in monograph

  1. SUCMAN, Natalia, MAKAEV, Fliur. Photosensitive nanopesticides for environmentally friendly and sustainable agriculture. In: Environmental and Technological Aspects of Redox Processes.  Pennsylvania, SUA: 2023, pp. 188-211. ISBN 979-836930514-0, 979-836930512-6. DOI: 10.4018/979-8-3693-0512-6.ch011

Abstracts

  1. DUCA, G., SUCMAN, N., MACAEV, F. Synthesis of spirooxindoles and study of their antiviral activity. In: Proceedings Of International Congress “By Promoting Excellence We Prepare The Future” - Selection Of Abstracts. 2 - 5 March 2023 Iaşi, România, p. 370. https://ijmd.ro/2023/proceedings-of-international-congress-by-promoting-excellence-we-prepare-the-future-selection-of-abstracts-2-5-march-2023/
  2. COJOCARI, S., BILAN, D., SUCMAN, N., STĂNGACI, E., MACAEV, F.. Transforming the five-membered ring d in a pregnenolone derivative into a six-membered ring through skeletal rearrangement. In: New frontiers in natural product chemistry, 12-13 octombrie 2023, Chișinău, Republica Moldova, p. 29. DOI: 10.19261/nfnpc.2023.ab22
  3. BILAN, D., COJOCARI, S., POGREBNOI, V., SUCMAN, N., MACAEV, F. The opening of dehydropregnenolone epoxide leading to the non-saturated skeletal rearrangement product. In: New frontiers in natural product chemistry, 12-13 octombrie 2023, Chișinău, Republica Moldova, p. 30. DOI: 10.19261/nfnpc.2023.ab23
  4. SUCMAN, N. Nucleophilic addition of pyridine amines to the double bond of in situ generated morita-baylis-hillman adducts from indole-2,3-dione. In: New frontiers in natural product chemistry, 12-13 octombrie 2023, Chișinău, Republica Moldova. p. 26. DOI: 10.19261/nfnpc.2023.ab19
  5. SUCMAN, N. Diastereoselective synthesis of a novel cyclic derivative based on 2,3-indolinedione. In: New frontiers in natural product chemistry, 12-13 octombrie 2023, Chișinău, Republica Moldova. p. 25. DOI: 10.19261/nfnpc.2023.ab18
  6. POGREBNOI, V., SUCMAN, N., MACAEV, F. The amides of dehydroabietic acid in synthesys of spiropyranes with the participation of carbonyl compounds.  In: New frontiers in natural product chemistry, 12-13 octombrie 2023, Chișinău, Republica Moldova. p. 23. DOI: 10.19261/nfnpc.2023.ab16
  7. POGREBNOI, V., SUCMAN, N., MAKAEV, F. The spirocyclopropane with fragments of dehydroabietic acid and aminooxindole. In: New frontiers in natural product chemistry, 12-13 octombrie 2023, Chișinău, Republica Moldova. p. 22. DOI: 10.19261/nfnpc.2023.ab15
  8. SUCMAN, N., COJOCARI, S., BILAN, D., MACAEV, F. Applying NMR for the detection of unusual reaction products of steroids. În: “BOOK OF ABSTRACTS”, Central European NMR Symposium & Bruker Users Meeting, 13-15 September 2023, Praga, Cehia,  P.32
  9. SUCMAN, N., COJOCARI, S., BILAN, D., POGREBNOI, V., MACAEV, F. Applying NMR for ascertaining the product's structure of unexpected dehydropregnenolone moiety skeletal rearrangement. În: “BOOK OF ABSTRACTS”, Central European NMR Symposium & Bruker Users Meeting, 13-15 September 2023, Praga, Cehia, P.32
  10. SUCMAN, N., CALINICENCO, S., MACAEV, F. Using NMR analysis to identify unconventional adducts of indole-2,3-dione. În: “BOOK OF ABSTRACTS”, Central European NMR Symposium & Bruker Users Meeting, 13-15 September 2023, Praga, Cehia,  P.31