Antitumor activity of derivatives of neplanocin A in vivo and in vitro.

Neplanocin A is a cyclopentenyl analog of adenosine which has been isolated from the culture filtrate of Ampullariella reqularis. Antitumor activity of twenty three derivatives of neplanocin A was examined against L1210, sarcoma 180 and L5178Y. Neplanocin A showed a marked inhibition of growth of L1210 in vivo. Other derivatives which had a 2' or 3'-substituted cyclopentene group showed weak cytotoxicity against L5178Y cells in vitro. Neplanocin A inhibited the biosynthesis of ribonucleic acid (RNA) and protein, while 6-chloroneplanocin A, a new active derivative, showed a specific inhibition of only RNA synthesis. The two hydroxy groups in the cyclopentene moiety with a ribose type structure are important for marked antitumor activity.