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

Khusnutdinova, É. F.; Petrova, А. V.; Thu, Hà Nguyễn Thị; Tu, Anh Le Thi; Thanh, T. Nguyen; Thi, Cham Ba; Babkov, Denis A.; Казакова, О. Б.

doi:10.1016/j.bioorg.2019.102957

Cited by 44 publications

(27 citation statements)

References 48 publications

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“…Substances were detected by 10% H 2 SO 4 with subsequent heating to 100-120 • C for 2-3 min. Betulonic aldehyde [24], compounds 1 [20], 3 [21], ursonic acid and 4 [22], 11 [23] were obtained according to the methods described previously.…”

Section: General Methods and Physical Measurementsmentioning

confidence: 99%

“…The following p-TsOH catalyzed rearrangement of compound 1 resulted in azepanoallobetulin 2 with a yield of 86%. Reduction of lupane A-azepanono-C28-nitryl 3 [21] and 2-cyano-3,4-seco-ursolic acid 4 [22] with LiAlH 4 under reflux in tetrahydrofurane led to methylenamino-derivatives 5 and 6. Betulin and C28-hydroxy-triterpenoids 1 or 6 were converted to corresponding aldehydes and were reacted with spermidine in MeOH under reflux to obtain aldimines 7-9 in yields of 65-72%.…”

Section: Chemistrymentioning

confidence: 99%

“…A mixture of compound 3 [21] (225 mg, 0.5 mmol) or compound 4 [22] (226 mg, 0.5 mmol) and LiAlH 4 (230 mg, 0.65 mmol) in dry THF (20 mL) was refluxed for 3 h and then poured into a 5% HCl solution (100 mL). The crude product was extracted with CHCl 3 (3 × 40 mL), and then the organic layer was washed with H 2 O, dried over CaCl 2 and evaporated under reduced pressure.…”

Section: Synthesis Of 5 Andmentioning

confidence: 99%

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A-Ring-Modified Triterpenoids and Their Spermidine–Aldimines with Strong Antibacterial Activity

Казакова

Brunel

Khusnutdinova

et al. 2019

Molbank

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Synthesis of A-ring-modified lupane, oleanane and ursane type triterpenoid conjugates with spermidine through an aldimine linkage or diethylentriamine via an amide bond is described. These derivatives were evaluated for their in vitro antimicrobial properties against human pathogens. Except for derivatives 1 and 7, all compounds have moderate to weak minimum inhibitory concentrations (MICs) against Gram-positive Staphylococcus aureus bacteria, with MICs varying from 3.125 to 200 µM. Compound 11 is efficient against Escherichia coli and Pseudomonas aeruginosa, with MICs of 25 and 50 µM, respectively, while all other derivatives do not possess important antimicrobial activities against these Gram-negative bacteria.

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Section: General Methods and Physical Measurementsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Section: Synthesis Of 5 Andmentioning

confidence: 99%

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A-Ring-Modified Triterpenoids and Their Spermidine–Aldimines with Strong Antibacterial Activity

Казакова

Brunel

Khusnutdinova

et al. 2019

Molbank

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“…Pentacyclic triterpenoids, including lupane type, are a well-known source of potent α-glucosidase inhibitors [ 55 , 56 , 57 , 58 ]. Moreover, certain triterpenoids were described to combine cytotoxicity towards cancer cells and α-glucosidase inhibitory properties [ 59 , 60 ].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2020

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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.

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“…The IC 50 value of ursolic acid modified with 5-methylindole moiety was comparable to doxorubicin [6], and the chloro-derivative of indolo-betulinic acid was found to be very active towards several cancer cell lines [7]. According to previous reports, some indolo-fused lupanes showed α-glucosidase inhibitory activity [8][9][10]. 2,3-Indolouvaol and 2,3-indolo-28-cyanoethoxybetulin showed antiproliferative activity in vitro towards leukemia, lung, and colon cancer cells [11].…”

Section: Introductionmentioning

confidence: 85%

N-Propargylation of Indolo-Triterpenoids and Their Application in Mannich Reaction

Khusnutdinova

Petrova

Bashirova

et al. 2019

Molbank

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

Cited by 44 publications

References 48 publications

A-Ring-Modified Triterpenoids and Their Spermidine–Aldimines with Strong Antibacterial Activity

A-Ring-Modified Triterpenoids and Their Spermidine–Aldimines with Strong Antibacterial Activity

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

N-Propargylation of Indolo-Triterpenoids and Their Application in Mannich Reaction

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