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DESIGN, SYNTHESIS, BIOLOGICAL EVALUATION AND MOLECULAR DOCKING OF PYRROLE-BASED COMPOUNDS AS ANTIOXIDANT AND MAO-B INHIBITORY AGENTS

EMILIO MATEEV 1*, BORISLAV ANGELOV 2, MAGDALENA KONDEVA-BURDINA 2, IVA VALKOVA 3, MAYA GEORGIEVA 1, ALEXANDER ZLATKOV 1

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Alzheimer’s disease (AD) is the most widespread neurodegenerative disorder with a significant impact on health systems. Considering the lack of efficient treatment, compounds with multi-target activities are usually designed as promising options to fill the evident gap. In this study, two novel N-pyrrolyl carboxylic acids (4a and 5a) and eight corresponding amide derivatives (4a1-4a3 and 5a1-5a5) were synthesized and fully elucidated by 1H NMR, FT-IR and HRMS (high resolution mass spectrometry). All reported compounds were assessed for their radical (DPPH and ABTS+●) scavenging properties and MAOB blocking potential. The results indicated that compound 5a2 could serve as a prominent lead compound for a future optimization as a MAO-B inhibitor. In addition, the DPPH and ABTS+● assays demonstrated significant antioxidant capacity. A possible binding conformation of 5a2 in the active site of MAO-B was also identified through molecular docking simulations. The analysis of the major interactions indicated the establishment of several unfavourable steric clashes. Thus, reducing the size of the core structure could drastically increase the MAO-B antagonizing potency of the pyrrole-based compounds.