<i>In situ</i> hemisynthesis of new <i>meso</i> -substituted dipyrromethanes using natural aldehydes: <i>in vitro</i> anticholinesterase activity and <i>in silico</i> study
This study reports the <i>in situ</i> hemisynthesis of two novel dipyrromethanes (<b>DPM-1</b> and <b>DPM-2</b>) from ethyl 1,2-dimethyl-1H-pyrrole-3-carboxylate and natural aldehydes: perillaldehyde from <i>Ammodaucus leucotrichus</i> and cuminaldehyde from cumin seed essential oil. The compounds were synthesized <i>via</i> a double Friedel-Crafts reaction under two catalytic systems: (i) water/ethanol (1:1 v/v) with 0.18 M HCl, and (ii) iodine-catalyzed chloroform. Structural elucidation was achieved using <sup>1</sup>H NMR,<sup>13</sup>C NMR, HSQC, HMBC, and HR-MS. Both derivatives showed significant inhibitory activity against AChE and BChE. <b>DPM-2</b> was more active against AChE (IC<sub>50</sub> = 22.6 ± 0.06 μM) than <b>DPM-1</b> (IC<sub>50</sub> = 51 ± 1.74 μM), and comparable to Galantamine (IC<sub>50</sub> = 21.81 ± 1.15 μM). Regarding BChE, <b>DPM-2</b> (IC<sub>50</sub> = 115 ± 1.91 μM) exhibited greater inhibitory potency than <b>DPM-1</b> (IC<sub>50</sub> = 230.41 ± 0.75 μM), and remained close to Galantamine (IC<sub>50</sub> = 120.93 ± 1.99 μM). <i>In silico</i> analysis supported their potential as anti-Alzheimer's agents.
Authors
- Alexander V. Stepakov (ORCID: https://orcid.org/0000-0001-9470-1710)
- Ismahene Bazine (ORCID: https://orcid.org/0000-0001-6772-8379)
- Rafik Menacer (ORCID: https://orcid.org/0000-0002-3742-8727)
- Ramzi Maadadi (ORCID: https://orcid.org/0000-0002-1795-1684)
- Dominique Harakat (ORCID: https://orcid.org/0000-0001-5369-8703)
- Chafai Boukentoucha
- Chawki Bensouici
- Anthony Abou Dib
- Leonid Pevzner
- Mikhail Petrov
Institutions
- St Petersburg University (RU)
- Centre de Recherche sur l'Information Scientifique et Technique (DZ)
- Seva Mandir (IN)
- National Agency for the Development of Renewable Energy and Energy Efficiency (MA)
- Institute of Structural and Molecular Biology (GB)
- Chemical Pharmaceutical Research Institute (BG)
- Université de Reims Champagne-Ardenne (FR)
- St. Petersburg State Technological Institute (RU)
Publication Details
- Journal
- Natural Product Research
- Published
- 2026-03-27
- DOI
- https://doi.org/10.1080/14786419.2026.2648132
- Primary Topic
- Photochromic and Fluorescence Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.00