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Synthesis and Macrofilaricidal Activity of Substituted 2‐Hydroxy/5‐Hydroxy/2‐Methyl‐1,4‐Naphthoquinones
Author(s) -
Karunan Twinkle,
Mathew Nisha,
Srinivasan Lakshmy,
Muthuswamy Kalyanasundaram
Publication year - 2013
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21065
Subject(s) - lymphatic filariasis , ivermectin , diethylcarbamazine , albendazole , anthelmintic , microfilaria , filariasis , pharmacology , drug , toxicology , filarioidea , in vitro , motility , biology , chemistry , helminths , immunology , biochemistry , zoology , genetics
Preclinical ResearchLymphatic filariasis is a disfiguring disease caused by parasitic worms that destroy the human lymphatic system leading to substantial morbidity. The current drug of choice for the treatment of filariasis is diethylcarbamazine and ivermectin with albendazole which are only effective against the microfilaria, leaving the adult worm unaffected, requiring the development of “adulticidal drugs.” Thirty amino substituted 2‐hydroxy/5‐hydroxy/2‐methyl‐1,4‐naphthoquinones were synthesized via the reaction of 2‐hydroxy/5‐hydroxy/2‐methyl‐1,4‐naphthoquinones with different primary and secondary amines. Compounds 1–30 were evaluated for in vitro antifilarial activity against the adult bovine filarial worm S etaria digitata as assessed by worm motility and MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) reduction assays. The mutagenecity, tumerogenecity, irritantancy, reproductive toxicity, drug score, druglike, and cLog P properties were calculated using OSIRIS property predictor. Ten compounds showed macrofilaricidal activity with ED 50 values ranging between 0.086 and 7.6 μM . Taking into account the biological effects and the promising drug‐like profiles of these compounds, these represent valid leads for the development of antifilarial agents against adult filarial worm.