<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 ¹H NMR,¹³C 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 (IC₅₀ = 22.6 ± 0.06 μM) than <b>DPM-1</b> (IC₅₀ = 51 ± 1.74 μM), and comparable to Galantamine (IC₅₀ = 21.81 ± 1.15 μM). Regarding BChE, <b>DPM-2</b> (IC₅₀ = 115 ± 1.91 μM) exhibited greater inhibitory potency than <b>DPM-1</b> (IC₅₀ = 230.41 ± 0.75 μM), and remained close to Galantamine (IC₅₀ = 120.93 ± 1.99 μM). <i>In silico</i> analysis supported their potential as anti-Alzheimer's agents.