4541

This invention includes two new anthelmintic compounds. The compounds are (S)-5-ethynyl-anabasine and (S)-5-bromoanabasine. These compounds are both derivatives of the nicotine molecule and are agonists of a nicotinic ACh receptor. This invention may take advantage of the large market for animal parasiticides and the lack of existing patented drugs for deworming.

The current status of the invention is at the proof of concept stage.

Nematode parasites infect ~2 billion people world-wide and infections are treated and prevented by anthelmintic drugs, some of which act on nicotinic Acetyl Choline receptors (nAChRs). There is an unmet need for novel therapeutic agents because of concerns about the development of resistance. ISU researchers selected the Asu-ACR-16 receptor from a significant nematode parasite, Ascaris, as a pharmaceutical target and nicotine as the basic moiety to facilitate the development of a novel class of anthelmintics. Asu-ACR-16 was expressed in Xenopus oocytes and two-electrode voltage clamp electrophysiology and determined agonist concentration-current-response plots to estimate the potencies (EC50s) of the agonists. The researchers synthesized a novel agonist, (S)-5-ethynyl-anabasine, and show that it is more potent than other nicotine alkaloids on Asu-ACR-16. Other related (S)-5-ethynyl-anabasine derivatives have also been developed. Such agonists have the potential to circumvent drug resistance that has arisen following repeated treatment of nematode parasites with other classes of anthelmintic drugs and are a useful lead for anthelmintic drug development.

• Target nicotinic ACh receptor

• Based on easily derived chemical

• Can replace drugs to which resistance has been developed

• Potentially useful in both human and animal populations