Adverse effects of gossypol analogs on TM4 cell mitochondrial function

Three aqueous-soluble gossypol Schiff's bases, SP562: bis-8,8'-[(N-(2-(dimethylamino)ethyl]-iminomethylene]- 1,1',6,6',7,7'-hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-2,2'-binaphthalene dihydrochloride; SP563: bis-8,8'-[(N-(2-(diethylamino)ethyl]-iminomethylene]-1,1',6,6',7,7'- hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-2,2'-binaphthalene dihydrochloride; and SP564: bis-8,8'-[(N-(2-(diethylamino)propyl]-iminomethylene]-1,1',6,6',7,7'- [hexahydroxy-5,5'-diisopropyl-3,3'-dimethyl-2,2'-binaphthalene dihydrochloride, were examined for their effects on TM4 cell mitochondrial function and proliferation. Among the three gossypol analogs, SP562 had the most severe effect on decreasing TM4 cell population that accumulated rhodamine 123 into their mitochondria. This adverse effect exerted by SP562, however, was not as strong as that caused by (+/-) gossypol acetic acid of the same molarity. On the other hand, SP564 had the most severe effect on proliferation of TM4 cells. This severe effect was even more so than that caused by an equimolarity of (+/-) gossypol acetic acid.