Glycosyl and polyalcoholic prodrugs of lonidamine

• Published in: Bioorganic & medicinal chemistry 2008-04, Vol.18 (7), p.2445-2450
• Main Authors: Giorgioni, G., Ruggieri, S., Di Stefano, A., Sozio, P., Cinque, B., Di Marzio, L., Santoni, G., Claudi, F.
• Format: Article
• Language: English
• Subjects: Absorption; Administration, Oral; Alcohols - chemistry; Animals; Anticancer; Antineoplastic agents; Antineoplastic Agents - blood; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacokinetics; Biological and medical sciences; Cell Line, Tumor; General aspects; Glycosides - chemistry; Humans; Hydrolysis; Indazoles - blood; Indazoles - chemical synthesis; Indazoles - pharmacokinetics; Lonidamine; Medical sciences; Models, Chemical; Pharmacology. Drug treatments; Polyalcoholic; Polyhydric; Prodrug; Prodrugs - chemical synthesis; Prodrugs - metabolism; Rats; Solubility; Structure-Activity Relationship; Synthesis; Water - chemistry
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2008.02.046

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 log P 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. 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 log P 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.