1. Designing New Analogs for Streamlining the Structure of Cytotoxic Lamellarin Natural Products.
- Author
-
Tangdenpaisal, Kassrin, Worayuthakarn, Rattana, Karnkla, Supatra, Ploypradith, Poonsakdi, Intachote, Pakamas, Sengsai, Suchada, Saimanee, Busakorn, Ruchirawat, Somsak, and Chittchang, Montakarn
- Subjects
MOLECULAR structure of alkaloids ,NATURAL products ,DRUG lipophilicity ,AQUEOUS solutions ,ANTINEOPLASTIC agent synthesis - Abstract
Despite the therapeutic potential of marine-derived lamellarin natural products, their preclinical development has been hampered by their lipophilic nature, causing very poor aqueous solubility. In order to develop more drug-like analogs, their structure was streamlined in this study from both the cytotoxic activity and lipophilicity standpoints. First, a modified total synthetic route was successfully devised to construct a library of 59 systematically designed lamellarin analogs, which were then subjected to cytotoxicity and log P determinations. Along with the 25 first-generation lamellarins previously synthesized in our laboratory, the structure-activity and structure-lipophilicity relationships were extensively evaluated. Our results clearly indicated the additional structural requirements around the lamellarin skeleton which, when combined with those reported previously, can provide invaluable guidance for further modifications to increase the aqueous solubility of these compounds. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF