Multicomponent synthesis of 2-amino-tetrahydro-4 H -chromenes catalyzed by chitosan and evaluation of anti- Leishmania activity

Aim This study describes a sustainable synthetic methodology employing unmodified commercial chitosan as a recyclable catalyst for the synthesis of chromene derivatives and the evaluation of their in vitro activity against Leishmania infantum.Methods 2-Amino-tetrahydro-4H-chromene derivatives (4a–p) were synthesized through multicomponent reactions (MCRs) via a Knoevenagel–Michael mechanism using benzaldehydes, malononitrile, and dimedone (0.5 mmol each) in aqueous medium at 60°C, catalyzed by commercial chitosan.Results The methodology exhibited good selectivity, short reaction times (5–60 min), and satisfactory chromene yields (69–89%). Chitosan demonstrated excellent reusability, being recovered and reused for up to four cycles without significant loss of catalytic efficiency. The compounds 4a–p were evaluated in vitro against Leishmania infantum, showing moderate activity across the series (IC50 = 35.64–240.51 µM). Compound 4p stood out as the most active (IC50 = 4.62 µM) and maintained relevant activity against amastigotes (EC50 = 7.57 µM). In addition, it showed no significant toxicity (HC50 and CC50 >100 µM).Conclusion Direct use of unmodified commercial chitosan provides a simple, efficient, and recyclable catalytic system for chromene synthesis. This sustainable approach yielded compounds with promising antileishmanial activity, highlighting compound 4p as a promising lead for further investigation.