Antitumor and antimetastatic effects of betulonic acid amides in mice with transplantable Lewis carcinoma

Abstract

We studied the effects of four synthetic amides of betulonic acid containing amino acid fragments (d,l-alpha-alanine, beta-alanine, and their methyl esters) on the rate of growth and metastatic dissemination of transplantable Lewis lung carcinoma in C57Bl/6 mice. The test compounds were administered intragastrically in a single dose of 500 mg/kg. 3-[-oxo-20(29)-lupen-28-oilamino]-propionic acid suppressed primary tumor growth (by 26%) and decreased the number of lung metastases (by more than 2 times). Antitumor and antimetastatic activity of triterpenoids decreased after methylation of the amino acid fragment in betulonic acid.

Novel semisynthetic derivatives of betulin and betulinic acid with cytotoxic activity

“…Modifications of the parent structure of these compounds at these positions can produce potentially important derivatives, found to be more effective than the starting ones, thus making them appealing for further development as antitumour drugs. 18,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] Nitrogen-containing derivatives of 1 and 2, such as Betulin 1: R = CH 2 OH Betulinic acid 2: R = COOH amine derivatives, 21,23,35 oxime derivatives, 21,23,30 amino acid conjugates, 22 amide derivatives, 20,32 hydrazine 29 and hydrazone derivatives, [28][29][30]35 imidazolide derivatives, 37 and other N-heterocyclic derivatives 24,31,34,36 have been reported to possess antiproliferative effect against tumour cell lines.…”

Structure of the Liver in Mice with Transplanted Lewis Carcinoma during Polychemotherapy and Correction with Betulonic Acid and Its Derivatives

“…Betulonic acid (BA) and its derivatives, substances with high antioxidant, hepato-, nephro-, and cardioprotective activities and selective cytostatic effect on tumor cells, are promising correctors (and probably cytoprotectors) of toxic effects of cytostatics [4][5][6][7][11][12][13][14]. An important property of some triterpenoids is their capacity to inhibit metastatic activity of tumor cells.…”