Action of camptothecin and its derivatives on deoxyribonucleic acid.
Camptothecin, an antitumor alkaloid, induced alkali-labile linkages to supercoiled closed circular DNA. The induction was dependent on the concentration of salt, and the highest level of induction was obtained in the presence of 1.0 M NaCl. The active site was the OH group at the C-20 in the E ring. Camptothecin interacted with adenine base at the C-7 in the B ring which resulted in inhibition of hyperchromicity in heat denaturation of DNA. Replacement of the H group with a substituent whose chain length was longer than -CH2CH3, such as -CH2OCOCH2CH3 or -CH2(CH2)4CO2CH3, caused a loss of potency for the inhibition of hyperchromicity. In the presence of 1.0 M NaCl, camptothecin interacted with superhelical closed circular DNA at 37 degrees. The apparent number of binding sites per base-pair of superhelical DNA was about one hundredth of ethidium bromide according to the equilibrium dialysis experiment. An intercalative interaction was observed with poly(dG-dC) in a 4 M NaCl concentration, but not in 0.1 M NaCl. A similar intercalation was detected in brominated poly(dG-dC) in the physiological concentration of NaCl. Camptothecin seemed to intercalate into the Z-form region which was favorably induced in a negatively superhelical closed circular DNA.
D000468:Alkalies; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004278:DNA, Superhelical / Q000378:metabolism; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009691:Nucleic Acid Denaturation; D009994:Osmolar Concentration; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D000468:Alkalies; D004278:DNA, Superhelical; D004247:DNA; D002166:Camptothecin