An efficient nanocatalytic synthesis of a triazolopyrimidine carbonitrile with potent activity against Trichinella spiralis

Abstract

The emergence of drug resistance and the adverse effects associated with currently available antiparasitic drugs necessitate the exploration of novel heterocyclic scaffolds. An efficient synthetic approach was developed for the preparation of 6,8-diamino-5-(4-nitrophenyl)pyrido[3,2-e][1,2,4]triazolo[1,5-a]pyrimidine-7-carbonitrile (DNP-Triazolopyrimidine) using lanthanum hydroxide nanorods as an efficient heterogeneous nanocatalyst. The synthesized La(OH)₃ nanorods were thoroughly characterized by XRD, FT-IR, SEM, TEM, and surface area analysis, confirming their nanoscale structure and morphology. The catalytic system demonstrated high efficiency, considerably reducing the reaction time while providing a high product yield under mild reaction conditions. The synthesized DNP-Triazolopyrimidine was structurally characterized by FT-IR, ¹H NMR, and ¹³C NMR spectroscopy. Biological evaluation demonstrated significant in vitro antiparasitic activity of DNP-Triazolopyrimidine against Trichinella spiralis larvae and adult worms in a dose- and time-dependent manner, achieving complete larval mortality at 10 and 20 µg/mL and complete adult-worm mortality at 20 µg/mL after 96 h of exposure. The LC₅₀ values were 9.71 µg/mL for larvae and 3.16 µg/mL for adult worms. SEM examination revealed pronounced ultrastructural alterations in treated parasites, including cuticular rupture, blebbing, vesicle formation, and loss of annulations. Cytotoxicity evaluation using WI-38 normal fibroblast cells demonstrated comparatively low cytotoxicity (IC₅₀ = 51.61 ± 2.9 µM). In silico ADMET analysis provided preliminary information on the pharmacokinetic and safety profile of DNP-Triazolopyrimidine.