Synthesis and anticancer activity of aminopropoxytriterpenoids

Abstract

Triterpenoids with aminopropoxy groups in C-28 or C-3 and C-28 positions were synthesized from betulin, erythrodiol, uvaol, oleantriol and betulinic acid Nmethylpiperazinylamide by cyanoethylation and the following catalytic hydrogenolysis. Computational estimating activity spectra of the designed compounds pointed out on their probable antineoplastic and proapoptotic activities. Their in vitro cytotoxic activity was evaluated at the National Cancer Institute, USA. Aminopropoxy derivatives of betulin, erythrodiol and oleantriol demonstrated the highest cytotoxic activity toward the most of 60 used tumor cell lines. Bisaminopropoxyerythrodiol revealed in vivo significant antineoplastic activity toward five mouse solid transplantable tumors. The results of in silico investigations and the efficacy of compounds in a broad panel of cell lines in vitro and the activity of bisaminopropoxyerythrodiol on the in vivo tumor models strongly suggest aminopropoxytriterpenoids as promising compounds for further investigation as anticancer agents. Graphical Abstract

Evaluation of Cytotoxicity and α-Glucosidase Inhibitory Activity of Amide and Polyamino-Derivatives of Lupane Triterpenoids

“…Compound 12 showed only marginal inhibitory properties. Compounds 11 and 18 [ 19 ] have not only notable cytotoxic activity, but also inhibit endoplasmic reticulum α-glucosidase. Further studies should be performed to establish structural requirements for NAG inhibition and, moreover, to evaluate its contribution to antitumor activity in animal models that allow taking into account tumor invasiveness and vascularization.…”

“…Trodusquemine (spermine analog of squalamine) has tremendous potential both as an antiobesity and an antidiabetic pharmacotherapeutic [ 15 ]. The high biological activity of squalamine stimulated numerous studies on the design and synthesis of its analogs, including monoterpene [ 16 ] and triterpene-based derivatives [ 17 , 18 , 19 , 20 , 21 ]. Some triterpene–spermine conjugates form dynamic supramolecular networks in solutions which influence their cytotoxicity [ 22 ].…”

Synthesis and Сytotoxicity of A-Azepanobetulinic AcidN-Methyl-Piperazinylamide

“…Various methods of triterpenoid molecule delivery to biological targets are being actively studied. 6 One of the important pharmacophore groups in the triterpenoid modifications is the piperazinyl fragment responsible for various biological activities: antibacterial, 7 anticancer, 8,9 antiviral, 10,11 antimalarial, 12 α-glucosidase inhibitory, 13 antileishmanial, 14 antifungal, 15 etc. This paper reports on the synthesis and study of the cytotoxicity and antibacterial activity of a new triterpene conjugate with N-methylpiperazine.…”

“…One of the important pharmacophore groups in the triterpenoid modifications is the piperazinyl fragment responsible for various biological activities: antibacterial, 7 anticancer, 8,9 antiviral, 10,11 antimalarial, 12 α -glucosidase inhibitory, 13 antileishmanial, 14 antifungal, 15 etc.…”

Synthesis and Cytotoxicity of 28-N-Propargylaminoalkylated 2,3-Indolotriterpenic acids

“…In this paper, indole-fused triterpenic Mannich bases have been synthesized and biologically evaluated for their anticancer activity for the first time. Since the positive influence of N-alkyl-and N-acylpiperazine fragments on the biological/cytotoxic activity of triterpenes is well known [17][18][19], N-propargylated indolotriterpene acids 4-6 were conjugated to N-methylpiperazine and morpholine using the Mannich reaction (secondary amine, paraformaldehyde, NaOAc, CuI) to obtain the propargylaminoalkyl derivatives 7-12 in 69-75% yield after purification. The antitumor activity (cytotoxicity) of compounds 1-12 was investigated in vitro in 60 cell-lines of nine different human tumors using the method described by the American National Cancer Institute (NCI) [20,21].…”