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Jalmahanbetova, R. I.; Рахимова, Б. Б.; Ралдугин, В. А.; Bagryanskaya, I. Yu.; Gatilov, Yu. V.; Шакиров, М. М.; Kulyjasov, A. T.; Адекенов, С. М.; Толстиков, Г. А.

doi:10.1023/a:1023943830932

Cited by 10 publications

(3 citation statements)

References 3 publications

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“…Compounds that are analogs of natural phosphates are attracting great attention, since they, as a rule, are chemically more stable than the phosphates themselves and, therefore, may have a prolonged action [ 33 ]. In terms of the synthesis of new phosphorus-containing analogs of natural phosphates, potentially possessing high biological activity, dialkylphosphonate derivatives of arteannuin B, grossheimin, were obtained by a method similar to the synthesis of phosphorus derivatives of arglabin [ 34 , 35 , 36 ].…”

Section: Resultsmentioning

confidence: 99%

Syntheses Based on 3,4α-Epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide

Адекенов¹

2022

Molecules

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The sesquiterpene γ-lactone estafiatin 1, the molecule of which has a structure of 3,4α-epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide, is characteristic of plants of the genera Achillea L. and Artemisia L. of the Asteraceae family. This article presents the results of chemical modification for three reaction centers of the estafiatin molecule 1: epoxy cycle, exomethylene group conjugated with γ-lactone carbonyl, and exomethylene group in position С10=С14; and at the same time 33 new derivatives were synthesized, the structures of which were established based on physicochemical constants, spectral data (IR-, PMR-, 13C-NMR), and X-ray diffraction analysis. The stereo- and regiospecificity, as well as the chemoselectivity of the reaction based on estafiatin molecule 1, are discussed. The reactivity of the substrate is significantly influenced by the stereochemistry of its molecule, the nature of the reagent, and the reaction medium. Based on the results of in silico screening, derivatives of estafiatin with high binding energies for both DNA-topoisomerase I and DNA-topoisomerase II were identified. The values of the inhibitory dose of IC50 for estafiatin 1 and its derivatives were determined on cell lines of eight types of tumors. In vivo experiments of the samples made it possible to establish that estafiatin 1 and its derivatives have pronounced antitumor activity against Pliss lymphosarcoma, Walker’s carcinosarcoma, sarcoma 45, sarcoma-180, alveolar liver cancer PC-1, leukemia P-388 and L-1210, and sarcoma-45 resistant to 5-fluorouracil.

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Section: Resultsmentioning

confidence: 99%

Syntheses Based on 3,4α-Epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide

Адекенов¹

2022

Molecules

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“…1 H NMR (400 MHz, CDCl 3 , δ ppm): 7.92-7.83 (m, 2H, H19), 7.79-7.70 (m, 2H, H18), 5.55 (br s, 1H, H3), 4.10 (dd, J = 14.3, 6.0 Hz, 1H, H A 13), 4.01 (t, J = 10.1 Hz, 1H, H6), 3.91 (dd, J = 14.2, 7.4 Hz, 1H, H B 13), 2.88-2.81 (br d, J = 8.0 Hz, 1H, H5), 2.81-2.70 (m, 2H, H A 2, H11), 2.22-2.00 (m, 2H, H A 9, H B 2), 2.00-1.89 (m, 1H, H B 9), 1.91 (br s, 3H, H15), 1.76-1.62 (m, 1H, H A 8), 1.50-1.42 (m, 2H, H7, H B 8), 1.30 (s, 3H, H14). 13 C{ 1 H} NMR (100.6 MHz, CDCl 3 , δ ppm): 175.4 (C12), 168.2 (C16), 140.6 (C4), 134.3 (C19), 131.9 (C17), 125.0 (C3), 123.6 (C18), 82.5 (C6), 72.5 (C1), 62.7 (C10), 52.6 (C5), 52.0 (C7), 43.9 (C11), 39.6 (C2), 37.0 (C13), 33 1R,5R,6S,7S,10S,11R)-1(10)-Epoxy-guai-3-en-6,12-olide-13yl)methyl)oxazolidin-2-one 6 c. The crude product was purified by column chromatography (R f = 0.71, eluent n-hexane/EtOAc = 1 : 1). Yield 88 % (1.17 g), white powder, mp 87-88°C, [α] D 21 = + 71.2 (c 1.00; CHCl 3 ).…”

Section: -((1r5r6s7s10s11rmentioning

confidence: 99%

“…Adekenov and co-workers described hydrophosphorylation of arglabin using sodium dialkyl phosphites. [33] This reaction suffered from strongly substrate-dependent yields. For example, dimethyl phosphite reacted with a diminished efficiency.…”

Section: Introductionmentioning

confidence: 99%

Phosphine‐Catalyzed Synthesis and Cytotoxic Evaluation of Michael Adducts of the Sesquiterpene Lactone Arglabin

Salin,

Shabanov,

Khayarov

et al. 2024

ChemMedChem

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A general method for chemo‐ and diastereoselective modification of anticancer natural product arglabin with nitrogen‐ and carbon‐centered pronucleophiles under the influence of nucleophilic phosphine catalysts was developed. The locked s‐cis‐geometry of α‐methylene‐γ‐butyrolactone moiety of arglabin favors for the additional stabilization of zwitterionic intermediate by electrostatic interaction between phosphonium and enolate oxygen centers, leading to the unprecedentedly efficient phosphine‐catalyzed Michael additions to this sesquiterpene lactone. Using n‐Bu3P as the catalyst, pyrazole, phthalimide, 2‐oxazolidinone, 4‐quinazolinone, uracil, thymine, cytosine, and adenine adducts of arglabin were obtained. The n‐Bu3P‐catalyzed reaction of arglabin with active methylene compounds resulted in the predominant formation of bisadducts bearing a new quaternary carbon center. All synthesized Michael adducts and previously obtained phosphorylated arglabin derivatives were evaluated in vitro against eleven cancer and two normal cell lines, and the results were compared to those of natural arglabin and its dimethylamino hydrochloride salt currently used as anticancer drugs. 2‐Oxazolidinone, uracil, diethyl malonate, dibenzyl phosphonate, and diethyl cyanomethylphosphonate derivatives of arglabin exhibited more potent antiproliferative activity towards several cancer cell lines and lower cytotoxicity towards normal cell lines in comparison to the reference compounds, indicating the feasibility of the developed methodology for the design of novel anticancer drugs with better therapeutic potential.

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Synthesis and Biological Evaluation of Antitumor‐Active Arglabin Derivatives

Csuk

Heinold

Siewert

et al. 2011

Archiv der Pharmazie

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Arglabin derivatives varied at the endo- or exo-cyclic double bond were synthesized and studied in a colorimetric sulforhodamine B assay for their cytotoxicity. Variations on the endocyclic double bond led to compounds of reduced cytotoxicity whereas derivatives from the reaction of the α-methylene-γ-butyrolactone moiety led to compounds of similar or only slightly reduced cytotoxicity but different, cell line-dependent selectivity. In addition, arglabin is an excellent starting material for the synthesis of the guaianolide arborescin.

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Cited by 10 publications

References 3 publications

Syntheses Based on 3,4α-Epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide

Syntheses Based on 3,4α-Epoxy-1,5,7α,6β(H)-guai-10(14),11(13)-dien-6,12-olide

Phosphine‐Catalyzed Synthesis and Cytotoxic Evaluation of Michael Adducts of the Sesquiterpene Lactone Arglabin

Synthesis and Biological Evaluation of Antitumor‐Active Arglabin Derivatives

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