Studies on structure-activity relationship of gossypol, gossypol ethers and three naphthaldehydes in the inhibition of spermatozoal metabolism.

Gossypol tetramethyl ether [C30 H24 O2(OCH3)4] and gossypol hexamethyl ether [C30 H24 O2(OCH3)6], which in contrast to gossypol are stable compounds, were tested for their ability to depress fructose degradation in fresh human sperm cells. Both ethers inhibited spermatozoal fructolysis, yet less effectively than did the parent compound. A synthetic compound, O-hydroxylnaphthaldehyde, and two commercially available preparations, 1- and 2-naphthaldehydes, were also tested under the same experimental conditions. These preparations represent about half of the gossypol molecule and possess a reactive aldehyde group in their molecules. Their inhibitory effect on fructose degradation in fresh human sperm cells, however, was considerably smaller than that of gossypol itself. It thus appears that the whole ring structure of gossypol rather than the intact aldehyde group is required for an effective inhibition of spermatozoal energy metabolism.