An efficient synthesis of bis(indolyl)methane and 3,3-di(indol-3-yl) indolin-2-one synthesized using a novel heterogeneous catalyst (Fe₃O₄@L-Pro-SO₃H) under green protocol conditions. The catalyst showed promising catalytic activity, producing products in very short reaction times of 50–60 min with excellent yields (up to 95%), while being magnetically recovered and reused for up to four cycles without significant loss of its activity under optimized reaction conditions (ethanol, reflux). The synthesized compounds were analyzed spectroscopically ( 1 H/ 13 C NMR, LC–MS), and drug-likeness was analyzed via Swiss ADME, which confirmed that the compounds were in accordance with Lipinski's rule of five. Computational investigations using molecular docking revealed strong binding affinity of −6.2 and 7.6 kcal/mol for compounds 3a and RAS, respectively, and dynamics simulations (100 ns) confirmed the stability of the interactions of these compounds with the target MAO-B enzyme, with a binding energy of −139.94 ± 11.0 and − 87.40 ± 11.12 kJ/mol for 3a and RAS compounds, respectively. In vivo studies in a rotenone-induced zebrafish Parkinson model validated the neuroprotective potential of lead compound 3a, which substantially ameliorated locomotor activity (47.5 ± 1.44 s, *** p < 0.001) and social interaction (31.25 ± 1.25 s, *** p < 0.001), restored increased anti oxidative activity SOD (** p < 0.01), GSH (*** p < 0.001), and decreased oxidative stress levels MDA (***p < 0.001), decreased inflammatory mediator activity MPO (***p < 0.001) and inhibited MAO-B (***p < 0.001). Histopathological studies revealed that 3a treated zebrafish brain PGZ cell morphology and population nearly to normal zebrafish. This represents the first integrated approach merging green nanocatalysis, computational modeling, and preclinical validation for the design of sustainable indole-based therapeutics for Parkinson's disease.
Mane et al. (Mon,) studied this question.