Novel NO-releasing derivatives of betulinic acid with antitumor activity

Synthesis of [2+1] Conjugates of Betulic Acid with α,ω-Diols

“…Another well-known synthetic approach to betulonic acid esters consists of the reaction of betulonic acid (1) with alkyl, aryl, and alkynyl bromides in DMF in the presence of K 2 CO 3 [9,21,27], with bromomethyl acetate in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in CH 2 Cl 2 and MeCN [10], with cholesterol and farnesol in the presence of PPh 3 and diethyl azadicarboxylate (DEAD) in THF [13], or with (5-aryl-1,3,4-oxadiazol-2-yl)methyl chloride in acetone in the presence of K 2 CO 3 and KI [14]. The reactions of acid 1 with dibromoalkanes Br(CH 2 ) n B (n = 3, 4, 5, 6) in DMF in the presence of K 2 CO 3 were usually carried out in a large (1 : 4) excess of bromides and led mainly (up to 70%) to the [1 + 1] reaction products [28], and [2 + 1] conjugates were not isolated.…”

Newly developed gas-assisted sonodynamic therapy in cancer treatment

“…Many endogenous gasotransmitters, such as NO and CO have shown great importance in cancer cell growth, proliferation, and metastasis by acting as signaling molecules in the TME 93 , 94 . It is widely acknowledged that these gasotransmitters regulate tumor-related processes with a biphasic pharmacological character by solidly binding to the heem iron center of hemoglobin in mitochondria 95 , 96 . In brief, the response to the action of therapeutic gases is concentration dependent.…”

The current scenario of furoxan hybrids with anticancer potential

“…The antiproliferative SARs of furoxan-betulinic acid hybrids 10 (IC 50 : 0.67-3.43 μM, MTT assay) against B16 and HepG2 cancer cell lines revealed that (1) the linear linker between furoxan and betulinic acid moieties was more favorable than the branched linker; (2) prolonging the carbon spacer decreased the activity; and (3) amide linker was better than ester and 1,2,3-triazole [30][31][32][33]. In particular, hybrids 10a,b (IC 50 : 0.67-1.96 μM) were found to be most active against B16 and HepG2 cancer cell lines, and the activity (IC 50 : 0.76 and 0.67 μM) was comparable to that of paclitaxel (IC 50 : 0.41 μM) against HepG2 cells.…”