Publications by authors named "Oxana Kazakova"

19 Publications

  • Page 1 of 1

Synthesis of messagenin and platanic acid chalcone derivatives and their biological potential.

Nat Prod Res 2021 May 10:1-10. Epub 2021 May 10.

Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.

The chalcone derivatives of 20-oxo-lupanes have been synthesised and screened for some types of biological activity. Ozonolysis of lupanes afforded 20-oxo-derivatives with the following condensation using different aromatic aldehydes by Claisen‒Schmidt reaction to the target compounds. The configuration of 19-[3-(pyridin-3-yl)-prop-2-en-1-one]-fragment was established by X-ray analysis. Screening of cytotoxic activity against NCI-60 cancer cell line panel revealed, that messagenin derivative has the highest activity with GI value ranged from 0.304 to 0.804 μM. A colorimetric SRB assay revealed for the 2,30-bis-furfurylidene derivative and 30-bromo-20-oxo-29-nor-3,28-diacetoxy-betulin cytotoxic activity against breast carcinoma MCF-7 and ovarian carcinoma A2780 cell lines. Compounds and acted also as inhibitors of the enzyme -glucosidase (from ) with IC values of 1.76 μM and 3.3 μM thus being 97- and 52-fold more active than standard acarbose. Antiviral potency of compounds and against HCMV, HSV-1 and HPV is also discussed.
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http://dx.doi.org/10.1080/14786419.2021.1922904DOI Listing
May 2021

A simple but unusual rearrangement of an oleanane to a taraxerane-28,14 β -olide.

Steroids 2021 Apr 27;172:108853. Epub 2021 Apr 27.

Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany. Electronic address:

Reaction of 3-O-acetyl-oleanolic acid (3) with formic acid/hydrogen peroxide at 100 °C for several hours provides an extraordinary but simple pathway to a taraxeran-28,14 β -olide type triterpenoid while the same reaction at 0 °C occurred without re-arrangement of the carbon skeleton, and an oleanane-28,13 β -olide was obtained instead. The products from these reactions were subjected to a cytotoxicity screening employing several human tumor cell lines showing the latter compound not cytotoxic while the former was cytotoxic especially for MCF-7 (breast adenocarcinoma), and FaDu (hypopharyngeal carcinoma) cells. The highest cytotoxicity, however, was observed for 3 β, 12α, 13 β -trihydroxy-oleanan-28-oic acid (6) holding with EC = 4.2 μM for MCF-7 tumor cells.
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http://dx.doi.org/10.1016/j.steroids.2021.108853DOI Listing
April 2021

Cytotoxic Potential of a-Azepano- and 3-Amino-3,4-SeCo-Triterpenoids.

Int J Mol Sci 2021 Feb 8;22(4). Epub 2021 Feb 8.

Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.

Semi-synthetic triterpenoids, holding an amino substituted seven-membered A-ring (azepano-ring), which could be synthesized from triterpenic oximes through a Beckmann type rearrangement followed by a reduction of lactame fragment, are considered to be novel promising agents exhibiting anti-microbial, alpha-glucosidase, and butyrylcholinesterase inhibitory activities. In this study, in an attempt to develop new antitumor candidates, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives of betulin, oleanolic, ursolic, and glycyrrhetinic acids were evaluated for their cytotoxic activity against five human cancer cell lines and non-malignant mouse fibroblasts by means of a colorimetric sulforhodamine assay. Azepanoallobetulinic acid amide derivative was the most cytotoxic compound of this series but showed little selectivity between the different human tumor cell lines. Flow cytometry experiments showed compound to act mainly by apoptosis (44.3%) and late apoptosis (21.4%). The compounds were further screened at the National Cancer Institute towards a panel of 60 cancer cell lines. It was found that compounds , , , , , , , , , and showed growth inhibitory (GI) against the most sensitive cell lines at submicromolar concentrations (0.20-0.94 μM), and their cytotoxic activity (LC) was also high (1-6 μM). Derivatives , , , , and demonstrated a certain selectivity profile at GI level from 5.16 to 9.56 towards K-562, CCRF-CEM, HL-60(TB), and RPMI-8226 (Leukemia), HT29 (Colon cancer), and OVCAR-4 (Ovarian cancer) cell lines. Selectivity indexes of azepanoerythrodiol at TGI level ranged from 5.93 (CNS cancer cell lines SF-539, SNB-19 and SNB-75) to 14.89 for HCT-116 (colon cancer) with SI 9.56 at GI level for the leukemia cell line K-562. The present study highlighted the importance of A-azepano-ring in the triterpenic core for the development of novel antitumor agents, and a future aim to increase the selectivity profile will thus lie in the area of modifications of azepano-triterpenic acids at their carboxyl group.
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http://dx.doi.org/10.3390/ijms22041714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914897PMC
February 2021

Allobetulone rearrangement to l8αH,19βH-ursane triterpenoids with antiviral activity.

Nat Prod Res 2020 Dec 8:1-11. Epub 2020 Dec 8.

Ufa Institute of Chemistry UFRC RAS, Ufa, Russian Federation.

Allobetulone E-ring rearrangement under treating with HClO in AcO under reflux afforded new triterpenoids: 3,28-diacetoxy-21-acetyl-2(3),20(21)-18α,19βH-ursandiene and 3,28-diacetoxy-2(3),18(19)-oleandiene . 18α,19βH-Ursanes were transformed at A- and E-rings into indolo- and bis-furfurylidene derivatives. Structure elucidation was performed using COSY, NOESY, HSQC and HMBC experiments, and X-Ray analysis for . The potential of newly obtained 18α,19βH-ursanes was evaluated against HCMV and HPV-11, the NCI-60 cancer cell panel and inhibition of α-glucosidase. All of the compounds have shown viral inhibition towards HCMV compared to standard drug Acyclovir. 3β-Acetoxy-21β-acetyl-20β,28-epoxy-18α,19βН-ursane showed moderate activity (EC 4.87 μM) towards the HCMV-resistant isolate (GDGr K17) compared to standard drug Cidofovir and was four times more potent than Ganciclovir. Compound inhibited the cell growth of the three melanoma and one colon cancer cell. 3-Oxo-21β-acetyl-20β,28-epoxy-18α,19βН-ursane and compound inhibited α-glucosidase with IC 28.0 µM and 4.0 µM being from 6 to 44 times more active than acarbose.
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http://dx.doi.org/10.1080/14786419.2020.1855159DOI Listing
December 2020

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

Molecules 2020 Oct 20;25(20). Epub 2020 Oct 20.

Laboratory of Metabotropic Drugs, Scientific Center for Innovative Drugs, Volgograd State Medical University, Novorossiyskaya st. 39, 400087 Volgograd, Russia.

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 GI 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 and the fungi . 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.
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http://dx.doi.org/10.3390/molecules25204833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587962PMC
October 2020

Antimycobacterial activity of azepanobetulin and its derivative: In vitro, in vivo, ADMET and docking studies.

Bioorg Chem 2020 11 28;104:104209. Epub 2020 Aug 28.

Faculty of Pharmacy, "Victor Babes" University of Medicine and Pharmacy, 2nd Eftimie Murgu Sq., Timisoara 300041, Romania. Electronic address:

The antimycobacterial investigation of azepanobetulin and its amide derivative was performed. Both compounds showed increased in vitro antibacterial activity on the H37Rv MTB strain in aerobic and anaerobic conditions. Basing on differences between MIC and IC values a predominant bactericidal effect for amide in contrast to azepanobetulin with a bacteriostatic antibacterial mechanism is defined. Both compounds showed a strong antibacterial effect against resistant MTB strains with amide derivative being slightly more active. Amide derivative also showed a higher antibacterial potency against non-tuberculous mycobacterial strains (M. avium, M. abscessus). Molecular docking studies showed that the inhibition of tuberculosinyl adenosine transferase (Rv3378c) could constitute an antimycobacterial mechanism of action for these triterpenic azepane derivatives. The pharmacokinetic profile was evaluated by ADMET studies and azepanobetulin showing the better results was evaluated by in vivo experiments. This compound has demonstrated a statistically significant antimycobacterial activity compared to control, but inferior to isoniazid. Our findings show that pentacyclic triterpene derivatives holding a seven-membered azepane A-ring are the promising template for the development of new agents with high antibacterial potential against M. tuberculosis H37Rv, non-tuberculous mycobacterial and drug- resistant strains.
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http://dx.doi.org/10.1016/j.bioorg.2020.104209DOI Listing
November 2020

Synthesis and cholinesterase inhibiting potential of A-ring azepano- and 3-amino-3,4-seco-triterpenoids.

Bioorg Chem 2020 08 10;101:104001. Epub 2020 Jun 10.

Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.

In this study, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives were synthesized from betulin, oleanolic, ursolic and glycyrrhetinic acids aiming to develop new cholinesterase inhibitors. Azepanobetulin, azepanoerythrodiol and azepanouvaol were modified to give amide and tosyl derivatives, while azepano-anhydrobetulines and azepano-glycyrrhetols were obtained for the first time. Oleanane and ursane type 3-amino-3,4-seco-4(23)-en triterpenic alcohols were synthesized by reducing the corresponding 2-cyano-derivatives accessible from Beckmann type 2 rearrangements. The compounds were screened in colorimetric Ellman's assays to determine their ability to act as inhibitors for the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum). While most of these compounds were only moderate inhibitors for AChE, several of them were shown to be inhibitors for BChE acting as mixed-type inhibitors. Azepanobetulin 1, its C28-amide derivatives 7 and 8, azepano-11-deoxo-glycyrrhetol 12 and azepanouvaol 18 held inhibition constants K ranging between 0.21 ± 0.06 to 0.68 ± 0.19 μM. Thus, they were approximately 4 to 10 times more active than standard galantamine hydrobromide. For all of the compounds reasonably high docking scores for BChE were obtained being in good agreement with the experimental results from the enzymatic studies. As a result, A-ring azepano-triterpenoids were found to be new scaffolds for the development of BChE inhibitors.
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http://dx.doi.org/10.1016/j.bioorg.2020.104001DOI Listing
August 2020

The Introduction of Hydrazone, Hydrazide, or Azepane Moieties to the Triterpenoid Core Enhances an Activity Against .

Med Chem 2021 ;17(2):134-145

Institute of Biomedical Chemistry, 10 Pogodinskaya str., 119121, Moscow, Russian Federation.

Background: Triterpenoids exhibit a wide spectrum of antimicrobial activity.

Objective: The objective of this study was to synthesize a series of nitrogen derivatives based on lupane, oleanane, and ursane triterpenoids with high antitubercular activity.

Methods: Isonicotinoylhydrazones were prepared via the reaction of 3-oxotriterpenic acids or betulonic aldehyde with isoniazid (INH) in yields of 54-72%. N-Acylation of betulonic or azepanobetulinic acids led to lupane C28 hydrazides and dihydrazides. The derivatives were evaluated for their in vitro antimycobacterial activities against Mycobacterium tuberculosis (MTB) H37RV and single-drug resistance (SDR)-TB in the National Institute of Allergy and Infectious Diseases, USA. Molecular docking was performed to evaluate the possible binding modes of investigated compounds in the active site of Diterpene synthase (Rv3378c).

Results: The obtained compounds are represented by C3 or C28 conjugates with hydrazine hydrate or INH. Some compounds demonstrated from high minimum inhibitory concentration (MIC ≤ 10 μg/mL) to excellent (MICs from 0.19 to 1.25 μg/mL) activity against MTB H37RV. Two lupane conjugates with INH were the leading compounds against MTB H37RV and some SDR-strains with MICs ranged from 0.19 to 1.70 μg/mL. Molecular docking of active compounds to diterpene synthase showed that these moieties accommodate the active site of the enzyme.

Conclusion: It was revealed that the conjugation of lupanes with INH at C3 is more effective than at C28 and the lupane skeleton is preferable among oleanane and ursane types. The replacement of native hexacarbocyclic A ring to seven-member azepane ring is favorably for inhibition of both MTB H37RV and SDR-strains. These data could possibly mean that the antitubercular activity against INH-resistant strains (INH-R) came from both triterpenoid and isoniazid parts of the hybrid molecules. Azepanobetulin showed the highest activity against both INH-R strains in comparison with other triterpenoids and INH. Thus, the introduction of hydrazone, hydrazide (dihydrazide), or azepane moieties into the triterpenoid core is a promising way for the development of new anti-tubercular agents.
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http://dx.doi.org/10.2174/1573406416666200115161700DOI Listing
June 2021

Diastereoselective Synthesis of Triterpenoid 1,2,4-Trioxolanes by Griesbaum Co-ozonolysis.

J Nat Prod 2019 09 6;82(9):2550-2558. Epub 2019 Sep 6.

A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences , Moscow 119991 , Russian Federation.

Diastereoselective synthesis of triterpenoid 1,2,4-trioxolanes by Griesbaum co-ozonolysis was shown for the first time. Ozonolysis of 2-methoxyoximes (--isomers mixture) of allobetulin or methyl oleanoate with CF-ketones resulted in asymmetrical spiro-1,2,4-trioxolanes as mixtures of diastereomers in yields up to 80-85%. The configuration of the spiro-C-2 center of individual ozonides was determined by 2D NMR spectra and X-ray crystallographic analysis. The products of ozonolysis of triterpenoid 3-methoxyoximes were mixtures of regioisomeric methoxylactams. Thus, the fundamental differences in the oxidation of homologous triterpenoid 2- or 3-methoxyoximes with ozone have been established. These results may afford a new stage in the development of the Griesbaum method as applied to natural compounds and biologically active peroxides.
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http://dx.doi.org/10.1021/acs.jnatprod.9b00393DOI Listing
September 2019

Structural modifications of 2,3-indolobetulinic acid: Design and synthesis of highly potent α-glucosidase inhibitors.

Bioorg Chem 2019 07 29;88:102957. Epub 2019 Apr 29.

Ufa Institute of Chemistry UFRS RAS, 71 pr. Oktyabrya, Ufa 450054, Russian Federation.

A series of nineteen nitrogen-containing lupane triterpenoids was obtained by modification of C2, C3, C20 and C28 positions of betulonic acid and their α-glucosidase inhibiting activity was investigated. Being a leader compound from our previous study, 2,3-indolo-betulinic acid was used as the main template for different modifications at C-(28)-carboxyl group to obtain cyano-, methylcyanoethoxy-, propargyloxy- and carboxamide derivatives. 20-Oxo- and 29-hydroxy-20-oxo-30-nor-analogues of 2,3-indolo-betulinic acid were synthesized by ozonolysis of betulonic acid followed by Fischer indolization reaction. To compare the influence of the fused indole or the seven-membered A-ring on the inhibitory activity, lupane A-azepanones with different substituents at C28 were synthesized. The structure-activity relationships revealed that the enzyme inhibition activity dramatically increased (up to 4730 times) when the carboxylic group of 2,3-indolo-betulinic acid was converted to the corresponding amide. Thus, the IC values for glycine amide and L-phenylalanine amides were 0.04 and 0.05 μM, respectively. This study also revealed that 2,3-indolo-platanic acid is 4.5 times more active than the parent triterpenoid with IC of 0.4 μM. Molecular modeling suggested that improved potency is due to additional polar interactions formed between C28 side chain and a sub-pocket of the α-glucosidase allosteric site.
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http://dx.doi.org/10.1016/j.bioorg.2019.102957DOI Listing
July 2019

Synthesis of A-ring quinolones, nine-membered oxolactams and spiroindoles by oxidative transformations of 2,3-indolotriterpenoids.

Org Biomol Chem 2019 01;17(3):585-597

Ufa Institute of Chemistry - Subdivision of the Ufa Federal Research Centre of Russian Academy of Sciences, Ufa 450054, Russian Federation.

This paper describes an access to new nitrogen-containing heterocyclic triterpenoids by the reaction of 2,3-indolotriterpenoids with ozone and dimethyldioxirane. The oxidation of indolo-fused 28-oxo-allobetulin or methyl platanoate with ozone led to a mixture of a quinolone as the major product and a nine-membered 2,3-seco-2-oxolactam and three different types of spiroindoles as byproducts. The formation of quinolone and 2,3-seco-2-oxolactam derivatives could be explained by the standard 1,3-dipolar cycloaddition of ozone to the C2(3)-double bond of the triterpene core similar to the products observed in the ozonolysis of indoles in the Witkop-Winterfeldt oxidation (WWO). The formation of spiroindoles was unexpected and could be explained through the 1,2-cycloaddition of ozone to the C2(3)-double bond with consecutive intramolecular rearrangements of the 2,3-epoxy-intermediate. These spiroindoles seem to be novel structures observed in the WWO reaction. The formation of only two isomeric triterpene spiroindolinones was achieved by the oxidation of 2,3-indolo-28-oxo-allobetulin with dimethyldioxirane that could be explained by the rearrangement of the 2,3-epoxy-intermediate. 19β,28-Epoxy-18α-olean-28-oxo-2-nor-2,3-4'(1H)-quinolone was the most active against HPV-11 with EC50 0.45 μM and SI50 322 in a primary assay and SI90 < 10 against HPV-16 in a secondary assay. The oxidative transformations of indolotriterpenoids have great potential for further modifications towards the preparation of new biologically active compounds.
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http://dx.doi.org/10.1039/c8ob02624fDOI Listing
January 2019

Synthesis and antimycobacterial activity of triterpeni≿ A-ring azepanes.

Eur J Med Chem 2018 Jan 21;143:464-472. Epub 2017 Nov 21.

Arbuzov Institute of Organic and Physical Chemistry, Kazan Center of the Russian Academy of Sciences, Arbuzova st., 8, 420088, Kazan, Russian Federation.

A series of A-ring azepanones and azepanes derived from betulonic, oleanonic and ursonic acids was synthesized and evaluated for their in vitro antimycobacterial activities against M. tuberculosis (MTB) H37Rv and SDR-TB in the National Institute of Allergy and Infectious Diseases. Triterpenic A-azepano-28-hydroxy-derivatives were synthesized by the reduction with LiAlH of triterpenic azepanones available from the Beckmann rearrangement of the corresponding C3-oximes. Modification of azepanes at NH-group and atoms С12, C20, C28 and C29 of triterpenic core led to the derivatives with oxo, epoxy, aminopropyl, oximino and acyl substituents. The primary assay of tested triterpenoids against MTB H37Rv demonstrated their MIC values ranged from 3.125 to >200 μM. Ursane type A-azepano-28-cinnamoates were the most active being 2 and 4 times more efficient than the initial 28-hydroxy-derivative. The follow-up testing revealed A-azepano-28-cinnamoyloxybetulin as a leader compound with MIC 2 and MBC 4 μM against MTB H37Rv and MICs 4, 1 and 1 μM against INH, RIF and OFX resistant strains, respectively. Five oleanane and ursane azepanes pronounced better activity than isoniazid against INH-R1 and rifampicin against INH-R2 strains. This work opens a new direction in the design and synthesis of new antitubercular agents basing on azepanotriterpenoids.
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http://dx.doi.org/10.1016/j.ejmech.2017.11.035DOI Listing
January 2018

Synthesis and antimalarial activity of 3'-trifluoromethylated 1,2,4-trioxolanes and 1,2,4,5-tetraoxane based on deoxycholic acid.

Steroids 2018 01 24;129:17-23. Epub 2017 Nov 24.

A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 ul. Vavilova, 119991 Moscow, Russian Federation.

A series of new steroidal peroxides - 3'-trifluoromethylated 1,2,4-trioxolanes and 1,2,4,5-tetraoxanes based on deoxycholic acid were prepared via the reactions of the Griesbaum coozonolysis and peroxycondensation, respectively. 1,2,4-Trioxolanes were synthesized by the interaction of methyl O-methyl-3-oximino-12α-acetoxy-deoxycholate with CFC(O)CH or CFC(O)Ph and O as the mixtures of four possible stereoisomers at ratios of 1:2:2:1 and in yields of 50% and 38%, respectively. The major diastereomer of methyl 12α-acetoxy-5β-cholan-24-oate-3-spiro-5'-(3'-methyl-3'-trifluoromethyl-1',2',4'-trioxolane) was isolated via crystallization of a mixture of stereoisomers from hexane and its (3S,3'R)-configuration was determined using X-ray crystallographic analysis. Peroxycondensation of methyl 3-bishydroperoxy-12α-acetoxy-deoxycholate with CFC(O)CH or acetone led to 1,2,4,5-tetraoxanes in yields of 44% and 37%, respectively. Antimalarial activity of these new steroidal peroxides was evaluated in vitro against the chloroquine-sensitive (CQS) T96 and chloroquine-resistant (CQR) K1 strains of Plasmodium falciparum. Deoxycholic acid 3'-trifluoromethylated 1,2,4,5-tetraoxane demonstrated a good IC value against CQR-strain (IC (K1) = 7.6 nM) of P. falciparum. Tetraoxane with the acetone subunit demonstrated the best results among all tested peroxides with an IC value of 3 nM against the CQ-resistant K1 strain. In general, 1,2,4-trioxolanes of deoxycholic acid are less active than 1,2,4,5-tetraoxanes.
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http://dx.doi.org/10.1016/j.steroids.2017.11.008DOI Listing
January 2018

Inhibition of Alpha-Glucosidase by Synthetic Derivatives of Lupane, Oleanane, Ursane and Dammarane Triterpenoids.

Nat Prod Commun 2016 Jan;11(1):33-5

A variety of new and earlier synthesized lupane, oleanane, ursane and dammarane triterpenoids have been investigated for their inhibitory activity against α-glucosidase. 2,3-Indole-21 β-acetyl-20β,28-epoxy-18α,19βH-ursane and 3-oxo-3A-homo-3a-aza-20(S)-hydroxydammar-24(25)-ene were synthesized for the first time. The compounds 3, 4, 8-11 and 14 demonstrated strong in vitro inhibitory activity towards α-glucosidase with IC₅₀ values of 37.5-115.1 µM. 3-Deoxy-3a-homo-3a-aza-28-cinnamoyloxy-20(29)-lupene, with an IC₅₀ of 6.67 µM was 60-fold more active than the market drug acarbose.
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January 2016

One-pot synthesis of hollongdione from dipterocarpol.

Nat Prod Commun 2014 Oct;9(10):1417-20

A one-pot synthesis of a hybrid triterpenoid-steroid molecule, hollongdione (22,23,24,25,26,27-hexanordammar-3,20-dion), was achieved in a yield of 89%, based on the selective dehydration of dipterocarpol following ozonolysis. The structure of hollongdione was confirmed by X-ray analysis for the first time. Dammar-20(22),24(25)-dien inhibited the growth of Mycobacterium tuberculosis (strain H37Rv) in vitro with a MIC of 50 μg/mL.
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October 2014

Synthesis and anticancer activity of quinopimaric and maleopimaric acids’ derivatives.

Bioorg Med Chem 2014 Nov;22(22):6481-9

A series of quinopimaric and maleopimaric acids’ derivatives modified in the E-ring, at the carbonyl- and carboxyl-groups were synthesized and their in vitro cytotoxic activity was evaluated at the National Cancer Institute, USA. Methyl esters of dihydroquinopimaric, 1a,4a-dehydroquinopimaric, 2,3-epoxyquinopimaric, 1-ethylenketal-dihydroquinopimaric, 1-ethylenketal-4-hydroxyiminodihydroquinopimaric acids displayed an activity on renal cancer, leukemia, colon cancer and breast cancer cell lines in concentration 10(−5) M. Methyl 1,4-dihydroxyiminodihydroquinopimarate showed both a potent and broad spectrum of cytotoxic activity against NSC lung cancer, colon cancer, breast cancer, renal cancer and leukemia and revealed in vivo antineoplastic activity towards mouse solid transplantable mammary carcinoma Ca755 and colon adenocarcinoma AKATOL. The information about antineoplastic activity of the studied quinopimaric and maleopimaric acids’ derivatives will be used for hit to lead optimization in these chemical series.
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http://dx.doi.org/10.1016/j.bmc.2014.09.030DOI Listing
November 2014

An efficient oxyfunctionalization of quinopimaric acid derivatives with ozone.

Nat Prod Commun 2013 Mar;8(3):293-6

Institute of Organic Chemistry, Ufa Research Center of Russian Academy of Sciences, 71 Prospect Oktyabrya, 450054 Ufa, Russian Federation.

An access to oxyfunctionalized quinopimaric acid derivatives is reported. The ozonolysis of methyl dihydroquinopimarate occurs through 1,2-cycloaddition of ozone to the bridging double bond followed by intermolecular rearrangements and formation of nontrivial 4beta-hydroxy-4alpha,14alpha-epoxy-13(15)-ene derivative 2. The oxidation of methyl furfurilydene dihydroquinopimarate with ozone led to anhydride 5 and unexpected carboxymethyl substituted cyclopentane lactone 6. The structure of compound 6 was confirmed by X-Ray analysis of its methyl ester.
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March 2013

Betulin and ursolic acid synthetic derivatives as inhibitors of Papilloma virus.

Bioorg Med Chem Lett 2010 Jul 25;20(14):4088-90. Epub 2010 May 25.

Institute of Organic Chemistry, Ufa Research Center of the Russian Academy of Sciences, 71, Prospect Oktyabrya, 450054 Ufa, Russian Federation.

The synthesis of new betulin and ursolic acid derivatives and evaluation of their antiviral activity in vitro is reported. Betulin was modified at positions C-3, C-20 and C-28 to afford the derivatives with nicotinoyl-, methoxycynnamoyl-, alkyne and aminopropoxy-2-cyanoethyl-moieties. The two stage conversion of betulin to the new ursane-type triterpenoid by treatment of allobetulin with Ac(2)O-HClO(4) is suggested. Cyanoethylation of ursonic acid oxime led to cyanoethyloximinoderivative. According to the results of antiviral screening against human papillomavirus type 11 the selectivity index for tested triterpenoids has a range from 10 to 35 with no cellular cytotoxicity, the most remarkable activity was found for 3beta,28-di-O-nicotinoylbetulin. 3Beta,28-dihydroxy-29-norlup-20(30)-yne was also active against HCV replicon (EC(50) 1.32; EC(90) 16.82; IC(50) 12.41; IC(90) >20; SI(50) 9.4; SI(90) >1.19). 28-O-methoxycynnamoylbetulin was active against influenza type A virus (H1N1) (EC(50) 2; IC(50) >200; SI >100).
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http://dx.doi.org/10.1016/j.bmcl.2010.05.083DOI Listing
July 2010

(E)-17β,19-Epoxy-methano-17,23,24-tridemethyl-4-nor-5β,18α-olean-3-one oxime.

Acta Crystallogr Sect E Struct Rep Online 2009 May 14;65(Pt 6):o1262. Epub 2009 May 14.

In the penta-cyclic triterpenoide skeleton of the title mol-ecule, C(27)H(43)NO(2) [systematic name: (3E,3aS,5aR,5bR,7aR,11R,11aR,11bR,13aR,13bR)-5a,5b,10,10,13b-penta-methyl-icosa-hydro-1H-11,7a-(epoxy-methano)cyclo-penta-[a]chrysen-3-one oxime], the five-membered ring A has an envelope conformation, while the six-membered rings B-E adopt chair conformations. Rings A and B are cis-fused. The hydroximino group has an E configuration. Strong inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into helical chains.
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http://dx.doi.org/10.1107/S1600536809016675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2969752PMC
May 2009