Synthesis of cytotoxic novel 9,11-secosterol analogs: Structure/activity studies.
In an effort to determine the pharmaceutical utility and the structural requirements for activity against tumor cell lines, 30 novel 9,11-secosterol analogues with different side chains and degrees of oxidation at C-9 were synthesized starting from hecogenin. Evaluation of the synthesized compounds for cytotoxicity against KB, HeLa and MCF-7 cell lines revealed that some important structural features are required for activity. The presence of a cholesterol-type side chain, which appears to play a major role in determining the biological activity, the existence of a ketone functional at C-9 is also crucial for anticancer activity whereas hydroxyl/ketone function at C-22 on the side chain did not increase cytotoxicity.
Kongkathip
Boonsong
B
Natural Products and Organic Synthesis Research Unit (NPOS), Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand. fscibsk@ku.ac.th
Hasakunpaisarn
Anuch
A
Boonananwong
Suthinee
S
Kongkathip
Ngampong
N
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000737:chemistry; D005663:Furans / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D013141:Spiro Compounds / Q000737:chemistry; D013261:Sterols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005663:Furans; D013141:Spiro Compounds; D013261:Sterols; C520774:spiroketal; D002784:Cholesterol