Synthesis of 3-O-acyl/3-benzylidene/3-hydrazone/3-hydrazine/17-carboxyacryloyl ester derivatives of betulinic acid as anti-angiogenic agents.
New 3-O-acyl, 3-benzylidene, 3-hydrazone, 3-hydrazine, 17-carboxyacryloyl ester derivatives of betulinic acid (2-6, 8-11, 13, 17, 18, 21, and 22) were synthesized and evaluated in vitro for anti-angiogenic activity on endothelial cell cytotoxicity, specificity, and tube-formation ability. All derivatives reported here showed IC(50)<4 microg/mL. Compounds 3, 9, 10, 17, 21, and 22 have shown better cytotoxicity (IC(50)<1.2 microg/mL) than betulinic acid (1) and improved endothelial cell specificity (ECS>10) in some cases. Compounds 10, 17, and 18 have shown 20%, 32%, and 48% reduction in TLS, respectively, and were found better than betulinic acid (1). We have shown that 20,29-dihydrobetulinic acid derivatives have better anti-angiogenic activity as compared to betulinic acid or its other derivatives.
Mukherjee
Rama
R
Divisions of Experimental Oncology, Dabur Research Foundation, 22, Site IV, Sahibabad, Ghaziabad 201 010, UP, India.
Jaggi
Manu
M
Rajendran
Praveen
P
Srivastava
Sanjay K
SK
Siddiqui
Mohammad J A
MJ
Vardhan
Anand
A
Burman
Anand C
AC
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D019073:HT29 Cells; D006801:Humans; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D000094062:Betulinic Acid
D020533:Angiogenesis Inhibitors; D001597:Benzylidene Compounds; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid