Design and Synthesis of NO-releasing Betulinic Acid Derivatives as Potential Anticancer Agents.
A total of 16 targeted NO-releasing betulinic acid (BA) derivatives were designed and synthesized as potential anticancer agents. Most IC&lt;sub&gt;50&lt;/sub&gt; values were under 1.0 μM in vitro test against HepG2 and B16. The result suggested that derivatives of BA with α,β-unsaturated ketone skeleton possessed significant cytotoxic activities than the others, among which derivatives with three carbons in diol linker (15b and 15c) exhibited the highest anti-cancer activity. NO-releasing amount detection of partial target compounds suggested that NO-releasing amount of this series of BA derivatives positively correlates with their cytotoxic activities. The anti-angiogenic activity of partial target compounds on zebrafish embryos in our experiment did not show any effects on the SIVs, however, they exhibited different influence on ISVs, with only 15a and 15d better than the negative control.
Jinhong
J
Liu
Zifei
Z
Zhu
Jia
J
Tang
Qinghua
Q
Lin
Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tongjia lane, Nanjing 210009,China.
Li
L
Chen
Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tongjia lane, Nanjing 210009,China.
Jianbo
J
Sun
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015027:Zebrafish; D000094062:Betulinic Acid
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D020030:Nitric Oxide Donors; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid