Bithionol

Bithionol is an antibacterial, anthelmintic, and algaecide. It is used to treat Anoplocephala perfoliata (tapeworms) in horses and Fasciola hepatica (liver flukes). Bithionol is an antibacterial, anthelmintic, and algaecide. It is used to treat Anoplocephala perfoliata (tapeworms) in horses and Fasciola hepatica (liver flukes). Bithionol has been shown to be a potent inhibitor of soluble adenylyl cyclase, an intracellular enzyme important in the catalysis of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). Soluble adenylyl cyclase is uniquely activated by bicarbonate. The cAMP formed by this enzyme is associated with capacitation of sperm, eye pressure regulation, acid-base regulation, and astrocyte/neuron communication. It is related to the organochlorine hexachlorophene, which has been shown to be an isomer-specific inhibitor of soluble adenylyl cyclase. Bithionol has two aromatic rings with a sulfur atom bonded between them and multiple chlorine ions and hydroxyl groups coming off of the phenyl groups. These functional groups are capable of hydrophobic, ionic, and polar interactions. These intermolecular interactions are responsible for the binding of bithionol to the bicarbonate binding site of soluble adenylyl cyclase efficiently enough to cause competitive inhibition with the usual bicarbonate substrate. The side chain of arginine 176 within the bicarbonate binding site interacts significantly with the aromatic ring of the bithionol molecule. This allosteric, conformational change interferes with the ability of the active site of soluble adenylyl cyclase to adequately bind ATP to convert it into cAMP. Arginine 176 usually interacts with the ATP and other catalytic ions at the active site, so when it turns from its normal position to interact with the bithionol inhibitor, it no longer functions in keeping the ATP bound to the active site.