Study On The Synthesis Of Hydrocarbyl Substituted Salicylic Acid And Salicylamide Derivatives And Their Molluscicidal Activity

In China, zoonotic schistosomiasis, caused by Schistosoma japonicum, is a chronic debilitating disease in the south. The snail, Oncomelania hupensis, is the main agent responsible for the transmission of this disease. So snail control can be a powerful intervention tool as it essentially removes the intermediate host from the parasite’s life cycle, thus breaking transmission. Currently, niclosamide is the only commercially available molluscicide recommended by the WHO, However, its toxicity to aquatic animals is one of the many environmental problems. Novel environmentally friendly molluscidal agents, isolated from plants or synthesized natural products analogues, were focused in recent years.Ginkgolic acids (GAs) are extracted from the sarcotesta and leaves of Ginkgo biloba L, which represent a new group of potential molluscicidal agents that have been discovered in recent years. On the basis of our previous studies,18 4- and 5-alkylsalicylic acid derivatives, including Z/E isomers and their saturated products with different chain lengths (7-13 carbon atoms) have been synthesized from 4-and 5-methylsalicylic acid. And then 14 different long chain salicylamides are synthesized from saturated long chain alkylsalicylic acids. The structures were elucidated by spectroscopic analyses.The alkylsalicylic acid derivatives’ molluscicidal effects against the host snail Oncomelania hupensis and acute fish toxicity against zebrafishs were evaluated. The results of the molluscicidal assays revealed that the lengths of the side chain play more important role. The activity was found to increase regularly with the growthing of the alkyl chain lengths, and the chain length with 13 carbon atoms showed strongest activity. The E-isomers and their saturated derivatives were better molluscicidal agents than their respective Z-isomers. The alkyl salicylamide derivatives show more active than that of corresponding saturated salicylic acid.The results of the acute fish toxicity assays revealed that all of the hydrocarbyl substituted salicylic acid derivatives in the test exhibited low toxicity to zebrafish. This result indicated that the synthesized salicylic acid derivatives were much safer than niclosamide in field use.