Glycosyl and polyalcoholic prodrugs of lonidamine.
Polyhydric alcohol derivatives of the anticancer agent lonidamine (LND) have been synthesized. The increased water solubility showed by prodrugs 4, 7, and 25 together with their logP values (2.19, 2.55, and 2.54, respectively) and chemical stability might be beneficial for prodrugs absorption after oral administration. Moreover, the new prodrugs undergo enzymatic hydrolysis in plasma and release LND demonstrating that they are promising candidates for in vivo investigations.
Giorgioni
G
G
Dipartimento di Scienze Chimiche, Università di Camerino, Via S. Agostino 1, 62032 Camerino (MC), Italy. gianfabio.giorgioni@unicam.it
Ruggieri
S
S
Di Stefano
A
A
Sozio
P
P
Cinque
B
B
Di Marzio
L
L
Santoni
G
G
Claudi
F
F
D000042:Absorption; D000284:Administration, Oral; D000438:Alcohols / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D006027:Glycosides / Q000737:chemistry*; D006801:Humans; D006868:Hydrolysis; D007191:Indazoles / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D008956:Models, Chemical; D011355:Prodrugs / Q000138:chemical synthesis / Q000378:metabolism*; D051381:Rats; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
D000438:Alcohols; D000970:Antineoplastic Agents; D006027:Glycosides; D007191:Indazoles; D011355:Prodrugs; D014867:Water; C016371:lonidamine