Abstract
Streptozotocin, a nitrosamide carcinogen, enhances the activity of guanylate cyclase. Six analogues of streptozotocin were studied in order to elucidate critical structure-activity relationships pertaining to the activation of guanylate cyclase. Analogue 1, known as chlorozotocin, has a nitroso group and increased guanylate cyclase activity 17 to 28-fold. Analogue III, which also has a nitroso group, but greater structural modifications with 4 acetate groups extending off of the glucose moiety, activated guanylate cyclase in colon but not in kidney. The other analogues (II,IV,VI, and VIII) lacking nitroso groups, either had no effect or produced mild decreases in guanylate cyclase activity.
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