Spermine amides of selected triterpenoid acids: dynamic supramolecular system formation influences the cytotoxicity of the drugs

Bildziukevich, Uladzimir; Malík, Matěj; Özdemir, Zülal; Rárová, Lucie; Janovská, Lucie; Šlouf, Miroslav; Šaman, David; Šarek, Jan; Nonappa, Nonappa; Wimmer, Zdeněk

doi:10.1039/c9tb01957j

Cited by 24 publications

(45 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…They are applicable in the screening tests in cancer cell lines, as we have proven several times in our previous papers [ 13 , 14 , 15 ]. In turn, we have already observed deviation of the experimental and calculated values [ 16 ]. Diosgenin ( 1 ) displays certain potential for a weak CNS active drug (cf.…”

Section: Discussionmentioning

confidence: 95%

“…Therefore, a more detailed investigation and/or optimization in the synthesis of 8 and 6 was made. We mostly focused on a behavior of the source molecules ( 7 and 5 ) during the synthesis, in which several procedures, earlier developed in our team, were used in the synthesis of triterpenoid acid derivatives, and in analogous reactions [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. A hypothesis on the course of the palladium-catalyzed hydrogenation in its employed modifications is postulated.…”

Section: Resultsmentioning

confidence: 99%

“…Nevertheless, they are applicable in the screening tests in cancer cell lines, as we have proven several times in our previous papers [ 13 , 14 , 15 ]. However, deviations of experimental and calculated values have already been observed [ 16 ]. The rules describe molecular properties important for a small molecule drug pharmacokinetics in the human body, including their absorption, distribution, metabolism, and excretion (known as ADME parameters).…”

Section: Resultsmentioning

confidence: 99%

“…Molecules 2019, 24, x FOR PEER REVIEW 3 of 14 molecules (7 and 5) during the synthesis, in which several procedures, earlier developed in our team, were used in the synthesis of triterpenoid acid derivatives, and in analogous reactions [10][11][12][13][14][15][16]. A hypothesis on the course of the palladium-catalyzed hydrogenation in its employed modifications is postulated.…”

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Synthesis and Pharmacological Effects of Diosgenin–Betulinic Acid Conjugates

et al. 2020

Self Cite

View full text Add to dashboard Cite

The target diosgenin–betulinic acid conjugates are reported to investigate their ability to enhance and modify the pharmacological effects of their components. The detailed synthetic procedure that includes copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (click reaction), and palladium-catalyzed debenzylation by hydrogenolysis is described together with the results of cytotoxicity screening tests. Palladium-catalyzed debenzylation reaction of benzyl ester intermediates was the key step in this synthetic procedure due to the simultaneous presence of a 1,4-disubstituted 1,2,3-triazole ring in the molecule that was a competing coordination site for the palladium catalyst. High pressure (130 kPa) palladium-catalyzed procedure represented a successful synthetic step yielding the required products. The conjugate 7 showed selective cytotoxicity in human T-lymphoblastic leukemia (CEM) cancer cells (IC50 = 6.5 ± 1.1 µM), in contrast to the conjugate 8 showing no cytotoxicity, and diosgenin (1), an adaptogen, for which a potential to be active on central nervous system was calculated in silico. In addition, 5 showed medium multifarious cytotoxicity in human T-lymphoblastic leukemia (CEM), human cervical cancer (HeLa), and human colon cancer (HCT 116). Betulinic acid (2) and the intermediates 3 and 4 showed no cytotoxicity in the tested cancer cell lines. The experimental data obtained are supplemented by and compared with the in silico calculated physico-chemical and absorption, distribution, metabolism, and excretion (ADME) parameters of these compounds.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis and Pharmacological Effects of Diosgenin–Betulinic Acid Conjugates

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…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 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

A series of two new and twenty earlier synthesized branched extra-amino-triterpenoids obtained by the direct coupling of betulinic/betulonic acids with polymethylenpolyamines, or by the cyanoethylation of lupane type alcohols, oximes, amines, and amides with the following reduction were evaluated for cytotoxicity toward the NCI-60 cancer cell line panel, α-glucosidase inhibitory, and antimicrobial activities. Lupane carboxamides, conjugates with diaminopropane, triethylenetetramine, and branched C3-cyanoethylated polyamine methyl betulonate showed high cytotoxic activity against most of the tested cancer cell lines with GI50 that ranged from 1.09 to 54.40 µM. Betulonic acid C28-conjugate with triethylenetetramine and C3,C28-bis-aminopropoxy-betulin were found to be potent micromolar inhibitors of yeast α-glucosidase and to simultaneously inhibit the endosomal reticulum α-glucosidase, rendering them as potentially capable to suppress tumor invasiveness and neovascularization, in addition to the direct cytotoxicity. Plausible mechanisms of cytotoxic action and underlying disrupted molecular pathways were elucidated with CellMinner pattern analysis and Gene Ontology enrichment analysis, according to which the lead compounds exert multi-target antiproliferative activity associated with oxidative stress induction and chromatin structure alteration. The betulonic acid diethylentriamine conjugate showed partial activity against methicillin-resistant S. aureus and the fungi C. neoformans. These results show that triterpenic polyamines, being analogs of steroidal squalamine and trodusquemine, are important substances for the search of new drugs with anticancer, antidiabetic, and antimicrobial activities.

show abstract

Synthesis and in vitro activity of oleanolic acid derivatives against Chlamydia trachomatis and Staphylococcus aureus

et al. 2021

View full text Add to dashboard Cite

Spermine amides of selected triterpenoid acids: dynamic supramolecular system formation influences the cytotoxicity of the drugs

Abstract: Cytotoxicity data: 8a: IC50 [μM]: 18.8/31.8/32.6/17.2 (25.1 ± 8.2), due to the dynamic self-assembly found, low-contrast networks (TEM); 8b: IC50 [μM]: 7.5 ± 1.6, dynamic self-assembly not detected, partly helical structures (TEM).

Cited by 24 publications

References 24 publications

Synthesis and Pharmacological Effects of Diosgenin–Betulinic Acid Conjugates

Synthesis and Pharmacological Effects of Diosgenin–Betulinic Acid Conjugates

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

Synthesis and in vitro activity of oleanolic acid derivatives against Chlamydia trachomatis and Staphylococcus aureus

Contact Info

Product

Resources

About