Anti-pinworm activity of novel coumarin-based trisubstituted methanes in Syphacia obvelata-infected mice. (December 2021) - Dhar, Errini Decruse
Abstract: The control of pinworms mainly relies on use of anthelmintic drugs. At present, there exists only few medications against pinworms, and their repeated use pose a serious risk of resistance development. Therefore, new anti-pinworm drugs are required to overcome the risk of resistance. This study reports the anti-pinworm activity of three novel coumarin-based trisubstituted methanes (TRSMs), i.e., 6-Amino-5-((4-hydroxy-2-oxo-2H-chromen-3-yl)(4-fluoro-phenyl)methyl)-1, 3-dimethyl-pyrimidine-2, 4(1H, 3H)-dione (1 ), 6-Amino-5-((4-hydroxy-2-oxo-2H-chromen-3-yl)(4-chlor-ophenyl)methyl)-1, 3-dimethyl-pyrimidine-2, 4(1H, 3H)-dione (2 ) and 6-Amino-5-((4-hydroxy-2-oxo-2H-chromen-3-yl)(4-bromophenyl)methyl)-1, 3-dimethyl-pyrimidine-2, 4(1H, 3H)-dione (3 ) in Syphacia obvelata -infected mice . The oral acute toxicity of compounds was examined using the OECD guidelines. The findings of this study reveal that TRSM analogues 1 and 2, at a single 80 mg/kg dose given for 5 days, can reduce about 90% of pinworm worm burden in mice, compared to 98% worm reduction shown by 20 mg/kg dose of albendazole, the reference drug, on the 12 day of infection. In particular, the fluoro-and bromo-substituents in the phenyl ring of synthesized derivatives greatly influence the efficacy of candidates. The oral acute toxicity of TRSMs was observed to be greater than 2000 mg/kg body weight for mice. Taken together, our study suggests that studied novel coumarin-based trisubstituted methanes could serve as suitable candidates for the development of new anti-pinworm drugs. Highlights: Enterobiasis is a common helminthic disease, especially in temperate climates. Anti-pinworm activity of three novel coumarin-based trisubstituted methanes is reported. Compounds showed high anti-pinworm effects in Syphacia obvelata -infected mice. Fluoro-and bromo-substituents in the phenyl ring of synthesized compounds greatly influenced the efficacy of candidates. Coumarin-based trisubstituted methanes could serve as promising candidates against pinworms.