Synthesis and study of mutagenic properties of lupane triterpenoids containing 1,2,3-triazole fragments in the C-30 position

Antimonova, A. N.; Petrenko, N. I.; Шакиров, М. М.; Rybalova, Т. V.; Фролова, Т. С.; Шульц, Э. Э.; Кукина, Т. П.; Синицына, О. И.; Толстиков, Г. А.

doi:10.1007/s10600-013-0702-1

Cited by 22 publications

(15 citation statements)

References 16 publications

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“…48 In addition to the linear products, they also obtained thiomorpholine 235 and 1,3-dipolar cycloaddition of diazomethane gave the spiro-pyrazole 236. 50 Some of the prepared compounds were analyzed for mutagenicity using the Ames test. The heterocyclic derivative 235 was considered biologically inactive; however, the remaining compounds, including 236, showed a good level of cytotoxicity, particularly compound 232 (IC 50 .…”

Section: Heterocycles With Heteroatoms Not Fused To the A-ringmentioning

confidence: 99%

Pentacyclic triterpenoids with nitrogen- and sulfur-containing heterocycles: synthesis and medicinal significance

et al. 2015

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Triterpenoids are natural compounds with a variety of biological activities and are usually produced by plants as secondary metabolites. In recent decades, scientists focused on the properties of triterpenoids have discovered many activities, such as antitumor, antiviral, antimicrobial, anti-inflammatory and others. Thousands of new triterpenoids with various skeletal modifications have now been synthesized. One of the most important modifications is the formation of a new heterocyclic ring. The simple fact that the vast majority of currently used drugs are heterocyclic compounds has encouraged a lot of researches to synthesize analogous triterpenoid derivatives in order to find new molecules with higher activities and consequently optimize their pharmacological profile. The biological properties of triterpenoid heterocycles are very promising and many of them have been studied, especially as antitumor agents. This review is mainly focused on the synthesis of various types of nitrogen and occasionally sulfur-containing heterocyclic triterpenoids for their potential use as future drugs in medicine and in addition discusses their overall biological activities.

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Section: Heterocycles With Heteroatoms Not Fused To the A-ringmentioning

confidence: 99%

Pentacyclic triterpenoids with nitrogen- and sulfur-containing heterocycles: synthesis and medicinal significance

et al. 2015

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“…Recently, a number of new articles were published on connecting a terpene with another molecule of interest via Huisgen 1,3-cycloaddition reaction. The first approach used terpenes substituted with alkynes in the position 3 [ 30 – 34 ], second approach used propargylesters or amides prepared at 28-COOH group [ 35 – 45 ], and the third approach used 30-azidoderivatives prepared via 30-bromoderivatives [ 46 ; 47 ]. Rarely, also position 2 is modified [ 48 ] or two position at once (3 and 30) in [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

“…could change the biological properties such as cytotoxicity or selectivity and the new compounds could act by different mechanism of action than the parent betulinic acid ( 1 ). Among the derivatives prepared by other research groups there are only few examples [ 46 ; 47 ] containing both free 28-carboxylic group and free 3-hydroxy group. In most cases, cycloaddition reactions were done with acid 1 protected as methyl ester or as acetate and the final molecules were also tested with the protective group on.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic conjugates of betulinic acid and substituted triazoles prepared by Huisgen Cycloaddition from 30-azidoderivatives

et al. 2017

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In this work, we describe synthesis of conjugates of betulinic acid with substituted triazoles prepared via Huisgen 1,3-cycloaddition. All compounds contain free 28-COOH group. Allylic bromination of protected betulinic acid by NBS gave corresponding 30-bromoderivatives, their substitution with sodium azides produced 30-azidoderivatives and these azides were subjected to CuI catalysed Huisgen 1,3-cycloaddition to give the final conjugates. Reactions had moderate to high yields. All new compounds were tested for their in vitro cytotoxic activities on eight cancer and two non-cancer cell lines. The most active compounds were conjugates of 3β-O-acetylbetulinic acid and among them, conjugate with triazole substituted by benzaldehyde 9b was the best with IC50 of 3.3 μM and therapeutic index of 9.1. Five compounds in this study had IC50 below 10 μM and inhibited DNA and RNA synthesis and caused block in G0/G1 cell cycle phase which is highly similar to actinomycin D. It is unusual that here prepared 3β-O-acetates were more active than compounds with the free 3-OH group and this suggests that this set may have common mechanism of action that is different from the mechanism of action of previously known 3β-O-acetoxybetulinic acid derivatives. Benzaldehyde type conjugate 9b is the best candidate for further drug development.

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“…This cycloaddition reaction gives 1,2,3-triazoles and has been widely used to synthesize 1,2,3-triazole-linked BA derivatives [14] (Scheme 18). This methodology allowed the functionalization of BA at positions 2 [55,59], 3 [54,60,61,62], 28 [20,26,63,64,65,66,67,68,69,70], and 30 [71,72,73], with different substrates, including peptides, approved drugs as AZT, β-cyclodextrins, sugars, and other triterpenes, as shown in the following examples.…”

Section: Click Chemistry—copper-catalyzed Azide-alkyne Cycloadditionmentioning

confidence: 99%

Recent Developments in the Functionalization of Betulinic Acid and Its Natural Analogues: A Route to New Bioactive Compounds

et al. 2019

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Betulinic acid (BA) and its natural analogues betulin (BN), betulonic (BoA), and 23-hydroxybetulinic (HBA) acids are lupane-type pentacyclic triterpenoids. They are present in many plants and display important biological activities. This review focuses on the chemical transformations used to functionalize BA/BN/BoA/HBA in order to obtain new derivatives with improved biological activity, covering the period since 2013 to 2018. It is divided by the main chemical transformations reported in the literature, including amination, esterification, alkylation, sulfonation, copper(I)-catalyzed alkyne-azide cycloaddition, palladium-catalyzed cross-coupling, hydroxylation, and aldol condensation reactions. In addition, the synthesis of heterocycle-fused BA/HBA derivatives and polymer‒BA conjugates are also addressed. The new derivatives are mainly used as antitumor agents, but there are other biological applications such as antimalarial activity, drug delivery, bioimaging, among others.

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Synthesis and study of mutagenic properties of lupane triterpenoids containing 1,2,3-triazole fragments in the C-30 position

Cited by 22 publications

References 16 publications

Pentacyclic triterpenoids with nitrogen- and sulfur-containing heterocycles: synthesis and medicinal significance

Pentacyclic triterpenoids with nitrogen- and sulfur-containing heterocycles: synthesis and medicinal significance

Cytotoxic conjugates of betulinic acid and substituted triazoles prepared by Huisgen Cycloaddition from 30-azidoderivatives

Recent Developments in the Functionalization of Betulinic Acid and Its Natural Analogues: A Route to New Bioactive Compounds

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