Tropolone alkaloids from Colchicum kurdicum (Bornm.) Stef. (Colchicaceae) as the potent novel antileishmanial compounds; purification, structure elucidation, antileishmanial activities and molecular docking studies

Natural compounds played an important role for prevention and treatment of the disease as well as are the important compounds for the design of the new bioactive compounds. In this study, eight tropolone Alkaloids were isolated from Colchicum kurdicum including colchicoside, 2-demethyl colchicine, 3-demethyl colchicine, demecolcine, colchifoline, N-deacetyl-N-formyl colchicine, colchicine and cornigerine by column and preparative thin layer chromatography. The chemical structures were identified by ¹H NMR and ¹³C NMR spectroscopy. Moreover, the antileishmanial activity on Leishmania major, anti-inflammatory activity, iron chelating activity and toxicity studies including hemolytic activity, brine shrimp toxicity, cytotoxicity and acute toxicity and docking study of all isolated bioactive compounds were evaluated. As result, colchicoside and colchicine had potent leishmanicidal effects and N-deacetyl-N-formyl colchicine and cornigerine had the highest anti-inflammatory effects. All compounds had the significant iron chelating activity. According to toxicity studies, isolated compounds showed the low hemolytic activity and cytotoxicity, high LC₅₀, LC₉₀ and LD₅₀. In the molecular docking study, colchicoside had the high dockscore. According to the study, with future studies all isolated compounds could be used for design the novel antileishmanial drugs.

Antileishmanial activity; Hemolytic activity; Iron chelating activity; PTLC; Tropolone alkaloid.