Synthesis and cytotoxic activity of substituted luotonin A derivatives.
Luotonin A is a cytotoxic alkaloid that has been shown to inhibit topoisomerase I via stabilization of the binary complex topoisomerase-DNA in the same fashion as camptothecin. The synthesis and the cytotoxic activity on the lung carcinoma cell line H460 of a series of derivatives of Luotonin A is reported. The compounds inhibit topoisomerase I but show weak cytotoxic activity, thus confirming the peculiarity of ring E of camptothecin for antitumor activity.
Dallavalle
Sabrina
S
Dipartimento di Scienze Molecolari Agroalimentari, Sezione di Chimica, Università di Milano, Via Celoria 2, 20133 Milano, Italy. sabrina.dallavalle@unimi.it
Merlini
Lucio
L
Beretta
Giovanni Luca
GL
Tinelli
Stella
S
Zunino
Franco
F
D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000633:toxicity; D006801:Humans; D011758:Pyrroles / Q000138:chemical synthesis* / Q000633:toxicity*; D011809:Quinones / Q000138:chemical synthesis* / Q000633:toxicity*; D059004:Topoisomerase I Inhibitors
D004791:Enzyme Inhibitors; D011758:Pyrroles; D011809:Quinones; D059004:Topoisomerase I Inhibitors; C480761:luotonin A; D004264:DNA Topoisomerases, Type I