Synthesis and Cytotoxicity of Lupane Mono- and Bis-Piperazinylamides

Giniyatullina, G. V.; Казакова, О. Б.

doi:10.1007/s10600-021-03453-4

Cited by 9 publications

(8 citation statements)

References 18 publications

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“…The cytotoxicity of 2-(furfurylidene)-betulonic acid against nine melanoma cell lines (LOX IMVI, MALME-3M, M14, MDA-MB-435, SK-MEL-2, SK-MEL-28, SK-MEL-5, UACC-257, and UACC-62) was remarkable, with the highest antiproliferative activity observed in UACC-62 (−97.61%), followed by MALME-3M (−82.26%), and SK-MEL-2 (−75.96%). In contrast, the 2-(pyridinoylidene)-betulonic acid has elicited the strongest antiproliferative effect on LOX IMVI (−9.49%), followed by SK-MEL-5 (89.4% inhibitory rate) and MDA-MB-435 (80.19% inhibitory rate) [ 87 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of In Vitro Antimelanoma and Antimicrobial Activity of 2,3-Indolo-betulinic Acid and Its Glycine Conjugates

Lombrea

Scurtu

Magyari-Pavel

et al. 2023

Plants

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Malignant melanoma is one of the most pressing problems in the developing world. New therapeutic agents that might be effective in treating malignancies that have developed resistance to conventional medications are urgently required. Semisynthesis is an essential method for improving the biological activity and the therapeutic efficacy of natural product precursors. Semisynthetic derivatives of natural compounds are valuable sources of new drug candidates with a variety of pharmacological actions, including anticancer ones. Two novel semisynthetic derivatives of betulinic acid—N-(2,3-indolo-betulinoyl)diglycylglycine (BA1) and N-(2,3-indolo-betulinoyl)glycylglycine (BA2)—were designed and their antiproliferative, cytotoxic, and anti-migratory activity against A375 human melanoma cells was determined in comparison with known N-(2,3-indolo-betulinoyl)glycine (BA3), 2,3-indolo-betulinic acid (BA4) and naturally occurring betulinic acid (BI). A dose-dependent antiproliferative effect with IC50 values that ranged from 5.7 to 19.6 µM was observed in the series of all five compounds including betulinic acid. The novel compounds BA1 (IC50 = 5.7 µM) and BA2 (IC50 = 10.0 µM) were three times and two times more active than the parent cyclic structure B4 and natural BI. Additionally, compounds BA2, BA3, and BA4 possess antibacterial activity against Streptococcus pyogenes ATCC 19615 and Staphylococcus aureus ATCC 25923 with MIC values in the range of 13–16 µg/mL and 26–32 µg/mL, respectively. On the other hand, antifungal activity toward Candida albicans ATCC 10231 and Candida parapsilosis ATCC 22019 was found for compound BA3 with MIC 29 µg/mL. This is the first report of antibacterial and antifungal activity of 2,3-indolo-betulinic acid derivatives and also the first extended report on their anti-melanoma activity, which among others includes data on anti-migratory activity and shows the significance of amino acid side chain on the observed activity. The obtained data justify further research on the anti-melanoma and antimicrobial activity of 2,3-indolo-betulinic acid derivatives.

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Section: Discussionmentioning

confidence: 99%

Comparison of In Vitro Antimelanoma and Antimicrobial Activity of 2,3-Indolo-betulinic Acid and Its Glycine Conjugates

Lombrea

Scurtu

Magyari-Pavel

et al. 2023

Plants

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“…Semisyntetické deriváty přírodních produktů jsou navrhovány za účelem zlepšení biologické dostupnosti (snížení hydrofobicity), překonání buněčné rezistence a posílení terapeutického účinku 3 . Tímto způsobem lze získat látky se zvýšenou biologickou aktivitou nebo zvýšenou selektivitou působení 3,10 .Triterpenoidy rostlinného původu jsou důležitým výchozím bodem pro syntézu strukturně rozmanitých derivátů 11 . Komplexace s cyklodextrinem a lipozomální nanoformulace byly jedním z přístupů ke zvýšení hydrofility látek.…”

Section: Syntéza Derivátůunclassified

“…Zavedením piperazinylové skupiny do triterpenoidních struktur dochází ke zvýšení biologických aktivit (protinádorové, antimikrobiální, antivirové, antimalarické, aj.) 11 . Deriváty mohou být strukturně modifikovány na kruhu A (C-3 a C-2), na karboxylové funkční skupině (vznik amidového nebo esterového postranního řetězce) 6 .…”

Section: Syntéza Derivátůunclassified

Betulonic and Platanic Acids as a Basis for the Synthesis of New Therapeutically Effective Substances

Černá,

Wimmer,

Massyagutova

et al. 2024

Chem. Listy

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Natural substances produced by plants represent an important source of new medicinal products. This article is focused on the description of the antimicrobial, antiviral, and cytotoxic activity of the synthesized derivatives of betulonic and platanic acids, especially their oxime-based derivatives. It is also aimed at providing overview of the possible use of these derivatives in the treatment of infectious or cancer diseases.

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“…tent micromolar inhibitor of yeast α-glucosidase and simultaneously inhibit endosomal reticulum α-glucosidase, rendering it potentially capable to suppress tumor invasiveness and neovascularization in addition to the direct cytotoxicity [265]. Using the described approach, 3β,20R,28-tri-(3-aminopropoxy)-betulin 240 [266,267] and 2-cyanoethoxy-241 and 3-aminopropoxy-betulinic N-methylpiperazinylamide 242 were synthesized and showed highly cytotoxic activities towards non-small cell lung, colon, breast, ovarian, leukemia, renal, melanoma, prostate and CNS cancer cells [264,268]. Triterpenoids with alkane polyamine fragments in the C28 side chain were synthesized on the basis of betulonic and oleanonic acids 243, 244.…”

Section: Terpene-and Triterpene-based Polyamine Derivativesmentioning

confidence: 99%

From Marine Metabolites to the Drugs of the Future: Squalamine, Trodusquemine, Their Steroid and Triterpene Analogues

Казакова

Giniyatullina

Babkov

et al. 2022

IJMS

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This review comprehensively describes the recent advances in the synthesis and pharmacological evaluation of steroid polyamines squalamine, trodusquemine, ceragenins, claramine, and their diverse analogs and derivatives, with a special focus on their complete synthesis from cholic acids, as well as an antibacterial and antiviral, neuroprotective, antiangiogenic, antitumor, antiobesity and weight-loss activity, antiatherogenic, regenerative, and anxiolytic properties. Trodusquemine is the most-studied small-molecule allosteric PTP1B inhibitor. The discovery of squalamine as the first representative of a previously unknown class of natural antibiotics of animal origin stimulated extensive research of terpenoids (especially triterpenoids) comprising polyamine fragments. During the last decade, this new class of biologically active semisynthetic natural product derivatives demonstrated the possibility to form supramolecular networks, which opens up many possibilities for the use of such structures for drug delivery systems in serum or other body fluids.

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Synthesis and Cytotoxicity of Lupane Mono- and Bis-Piperazinylamides

Cited by 9 publications

References 18 publications

Comparison of In Vitro Antimelanoma and Antimicrobial Activity of 2,3-Indolo-betulinic Acid and Its Glycine Conjugates

Comparison of In Vitro Antimelanoma and Antimicrobial Activity of 2,3-Indolo-betulinic Acid and Its Glycine Conjugates

Betulonic and Platanic Acids as a Basis for the Synthesis of New Therapeutically Effective Substances

From Marine Metabolites to the Drugs of the Future: Squalamine, Trodusquemine, Their Steroid and Triterpene Analogues

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