Synthesis of combinatorial libraries based on terpenoid scaffolds.
Triterpenoid-based scaffolds betulinic acid (1a) and ursolic acid (1b), have been used for the generation of combinatorial libraries in parallel format using solid phase organic synthesis method. These templates have the potential for the synthesis and amplification of triterpenoid-based compounds with one and two-point diversity. This has been demonstrated by the synthesis of two small libraries comprising 18 derivatives each of betulinic acid and ursolic acid with structural diversity at C-3 and C-28 positions. The primary screening of antimalarial activity of these libraries against P. falciparum in vitro led to the identification of four compounds with 5 fold increase in the activity compared to betulinic and ursolic acids.
Pathak
A
A
Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, 226 001, India.
Singh
S K
SK
Biabani
M A Farooq
MA
Kulshreshtha
D K
DK
Puri
S K
SK
Srivastava
S
S
Kundu
B
B
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical; D007202:Indicators and Reagents; D010084:Oxidation-Reduction; D010091:Oximes; D053978:Pentacyclic Triterpenes; D010963:Plasmodium falciparum / Q000187:drug effects; D012116:Resins, Plant; D013729:Terpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry; D000094062:Betulinic Acid; D000097245:Ursolic Acid
D000962:Antimalarials; D007202:Indicators and Reagents; D010091:Oximes; D053978:Pentacyclic Triterpenes; D012116:Resins, Plant; D013729:Terpenes; D014315:Triterpenes; D000094062:Betulinic Acid; D000097245:Ursolic Acid