1187569-38-5Relevant articles and documents
Rational design and semisynthesis of betulinic acid analogues as potent topoisomerase inhibitors
Abdel Bar, Fatma M.,Khanfar, Mohammad A.,Elnagar, Ahmed Y.,Liu, Hui,Zaghloul, Ahmed M.,Badria, Farid A.,Sylvester, Paul W.,Ahmad, Kadria F.,Raisch, Kevin P.,El Sayed, Khalid A.
experimental part, p. 1643 - 1650 (2010/03/31)
Chemical transformation studies were conducted on betulinic acid (1), a common plant-derived lupane-type triterpene. Eleven new rationally designed derivatives of 1 (2-5 and 7-13) were synthesized based on docking studies and tested for their topoisomerase I and IIR inhibitory activity. Semisynthetic reactions targeted C-3, C-20, and C-28 in 1. Structures of the new compounds were confirmed by spectroscopic methods (1D and 2D NMR and MS). Compound 9, 3-O-[N-(phenylsulfonyl)carbamoyl-17β-N-(phenylsulfonyl)amide]betulinic acid, showed 1.5-fold the activity of CPT in a topoisomerase I DNA relaxation assay. Four out of 14 betulinic acid analogues (5, 9, 11, and 12) showed 1.5-fold the activity of etoposide in a topoisomerase II assay. The new analogues exhibited better cytotoxic activities against the human colon cancer cells SW948 and HCT-116 and the breast cancer cell line MDA-MB-231 compared to the parent (1). Betulinic acid (1) is a potential scaffold for the design of new topoisomerase I and IIα inhibitors.
