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.
A
A
Hoshi
M
M
Yoshida
M
M
Iigo
R
R
Tokuzen
K
K
Fukukawa
T
T
Ueda
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D007930:Leucine / Q000378:metabolism; D007939:Leukemia L1210 / Q000473:pathology; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000473:pathology*; D012313:RNA / Q000096:biosynthesis; D012510:Sarcoma 180 / Q000473:pathology; D014529:Uridine / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; C049441:6-chloroneplanocin; D012313:RNA; C031096:neplanocin A; D007930:Leucine; D000241:Adenosine; D014529:Uridine