Synthesis and Biological Activity of 2,5-Dihydro-1,2-Oxaphosphole-2-Oxide Derivatives

Enchev, D. D.

doi:10.1007/7081_2009_4

Cited by 7 publications

(4 citation statements)

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“… 17 The recent reports on the biological activity evaluation studies of organophosphorus heterocycles reveal that this is a search thrust area with perpetual contributions. 18 Such inherent anticancer potentiality of α-aminophosphonates 19 − 25 has inspired us to design and synthesize some new 3-amino functionalized benzofused phospha-γ-lactones with a potential core of the 2,5-dihydro-1,2-oxaphosphole-2-oxide moiety 26 and investigate their pancreatic cell inhibition activity. Meanwhile, the previous methodologies for the synthesis of benzofused 2-phospha-γ-lactones involves the utility of precursors like aldols, 27 divinyl ethers, 26 acetylene carboxylic acids, 26 chalcones, 26 allenes, 28 , 29 and alkynyl systems 30 − 34 along with phosphorylating agents like dichlorophenylphosphines, 32 , 35 , 36 dichlorophenyl phosphineoxides, 37 triphenyl phosphine, 31 , 34 trialkylphosphite, 38 3-methylbuta-1,2-dien-1-ylphosphonic dichlorides, 39 allenyl phosphonates, 40 and dialkyl phosphites.…”

Section: Introductionmentioning

confidence: 99%

“…α-Aminophosphoryl functionality on a pharmacophoric core promotes antitumor activity and strongly inhibits the human tumor growth and induces apoptosis via the mitochondria-dependent pathway on safe and non-toxic grounds without affecting the normal cells . The recent reports on the biological activity evaluation studies of organophosphorus heterocycles reveal that this is a search thrust area with perpetual contributions . Such inherent anticancer potentiality of α-aminophosphonates − has inspired us to design and synthesize some new 3-amino functionalized benzofused phospha-γ-lactones with a potential core of the 2,5-dihydro-1,2-oxaphosphole-2-oxide moiety and investigate their pancreatic cell inhibition activity.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Anti-Pancreatic Cancer Activity Studies of Novel 3-Amino-2-hydroxybenzofused 2-Phospha-γ-lactones

et al. 2021

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A series of 3-amino-2-hydroxybenzofused 2-phosphalactones ( 4a–l ) has been synthesized from the Kabachnik–Fields reaction via a facile route from a one-pot three-component reaction of diphenylphosphite with various 2-hydroxybenzaldehyes and heterocyclic amines in a new way of expansion. The in vitro anti-cell proliferation studies by MTT assay have revealed them as potential Panc-1, Miapaca-2, and BxPC-3 pancreatic cell growth inhibitors, and the same is supported by molecular docking, QSAR, and ADMET studies. The MTT assay of their SAHA derivatives against the same cell lines evidenced them as potential HDAC inhibitors and identified 4a , 4b , and 4k substituted with 1,3-thiazol, 1,3,4-thiadiazol, and 5-sulfanyl-1,3,4-thiadiazol moieties on phenyl and diethylamino phenyl rings as potential ones. Additionally, the flow cytometric analyses of 4a , 4b , and 4k against BxPC-3 cells revealed compound 4k as a lead compound that arrests the S phase cell cycle growth at low micromolar concentrations. The ADMET properties have ascertained their inherent pharmacokinetic potentiality, and the wholesome results prompted us to report it as the first study on anti-pancreatic cancer activity of cyclic α-aminophosphonates. Ultimately, this study serves as a good contribution to update the existing knowledge on the anticancer organophosphorus heterocyclic compounds and elevates the scope for generation of new anticancer drugs. Further, the studies like QSAR, drug properties, toxicity risks, and bioactivity scores predicted for them have ascertained the synthesized compounds as newer and potential drug candidates. Hence, this study had augmented the array of α-aminophosphonates by adding a new collection of 3-amino-2-hydroxybenzofused 2-phosphalactones, a class of cyclic α-aminophosphonates, to it, which proved them as potential anti-pancreatic cancer agents.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Anti-Pancreatic Cancer Activity Studies of Novel 3-Amino-2-hydroxybenzofused 2-Phospha-γ-lactones

et al. 2021

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“…The versatile reactivity of 1,2-alkadienephosphonates, allowed them to be used as precursors for synthesis of complex organophosphorus compounds, which often exhibit certain biological activity [1].…”

Section: Introductionmentioning

confidence: 99%

Interaction of 1,2-alkadienephosphonates with propargyl alcohole

Iotova

Enchev

2019

Acta Scientifica Naturalis

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The reactivity of 1,2-alkadienephosphonates in nucleophilic addition reactions has been investigated.General procedure for preparation of 14 -17 To a solution of 6, 7, 8, 9, 10, 11, 12, or 13 in dry diethyl diethyl ether a 10% HCl was added and the mixture was stirring overnight. After standard work-up the residue was purified (hexane: ethylacetate 1:4). [3] Compound characterization 14. Dimethyl(3-methyl-2-oxopentyl)phosphonate, C 8 H 17 O 4 P; Calcd.: P 14.88, Found: P 14.66 %; IR: (cm -1 ) 1720 (C=C) , 1256 (P=O), 980 (P-O-C), 1 H NMR (CDCl 3 ): /ppm 3.39(d, 3 J HP 10.09Hz, 6H, (OMe)); 3.29(dt, 2 J HH 5.8Hz, 1H(CH)); 2.93(d, 2 J HP 11.9Hz, 2H(P-CH 2 )); 1.68(q, 3 J HH 7.0Hz, 3 J HH 8.0Hz, 2H(CH 2 -CH 3 )); 1.46(d, 3 J HH 6.8Hz, 3H, CHCH3)); 0.91(t, 3 J HH 8.0Hz, 3H, (CH 2 -CH3)); 31 P NMR(CDCl 3 ) /ppm: 31 P 17.1; pale yellow oil; Yield (%) 78 15. Methyl N,N-diethyl-P-(3-methyl-2-oxopentyl)phosphonoamidate, C 11 H 24 NO 3 P; Calcd.: P 12.42, Found: P 12.30 %; IR: (cm -1 ) 1700 (C=C) , 1238 (P=O), 980 (P-O-C), 1 H NMR (CDCl 3 ): /ppm 3.39(d, 3 J HP 10.09Hz, 3H, (OMe)); 3.09(t, 2 J HH 5.8Hz, 1H(CH)); 2.50(d, 2 J HP 11.9Hz, 2H(P-CH 2 )); 2.93(m, 3 J HP 13.6Hz, 3 J HH 7.2Hz, 2H, (CH 3 -CH 2 -N)); 1.00 (t, 3 J HH 7.2Hz, 3H, (CH 3 -CH 2 -N)); 1.68(q, 3 J HH 7.0Hz, 3 J HH 8.0Hz, 2H(CH 2 -CH 3 )); 1.40(d, 3 J HH 6.8Hz, 3H, CHCH3)); 0.89(t, 3 J HH 8.0Hz, 3H, (CH 2 -CH3)); 31 P NMR(CDCl3) /ppm: 31 P 16.9; pale yellow oil; Yield (%) 84 16. 1-(dimethylphosphoryl)-3-methylpentan-2-one C 8 H 17 O 2 P; Calcd.: P1 7.57, Found: P 17.49 %; IR: (cm -1 ) 1708 (C=C) , 1238 (P=O), 980 (P-O-C), 1 H NMR (CDCl 3 ): /ppm 3.09(t, 2 J HH 5.8Hz, 1H(CH)); 2.50(d, 2 J HP 11.9Hz, 2H(P-CH 2 )); 1.76(d, 2 J HP 16.6Hz, 6H(CH 3 -P)); 1.68(q, 3 J HH 7.0Hz, 3 J HH 8.0Hz, 2H(CH 2 -CH 3 )); 1.40(d, 3 J HH 6.8Hz, 3H, CHCH3)); 0.89(t, 3 J HH 8.0Hz, 3H, (CH 2 -CH3)); 31 P NMR(CDCl 3 ) /ppm: 31 P 17.6; oil; Yield (%) 81. 17. 1-(diphenylphosphoryl)-3-methylpentan-2-one, C 28 H 21 O 2 P; Calcd.: P 7.37, Found: P 7.17 %; IR: (cm -1 ) 1698 (C=C) , 1238 (P=O), 980 (P-O-C), 1 H NMR (CDCl 3 ): /ppm 7.29-7.17(m, 2H, (Ph)); 7.05(d, 2JHH 7.75Hz, 1H, (Ph)); 6.89(t, 2JHH 7.25Hz, 2H, (Ph)); 3.09(t, 2 J HH 5.8Hz, 1H(CH)); 2.50(d, 2 J HP 11.9Hz, 2H(P-CH 2 )); 1.68(q, 3 J HH 7.0Hz, 3 J HH 8.0Hz, 2H(CH 2 -CH 3 )); 1.40(d, 3 J HH 6.8Hz, 3H, CHCH3)); 0.89(t, 3 J HH 8.0Hz, 3H, (CH 2 -CH3)); 31 P NMR(CDCl3) /ppm: 31 P 17.0; oil; Yield (%) 85. ConclusionsThe results obtained by us confirm once again the general mechanism of the reaction of nucleophilic addition of alcohols to 1,2-alkadienephosphonates, i.e. with formation of 1,2-and 2,3adducts.

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“…The combination of double bonds and a phosphoryl group in the molecules of those compounds, each with different reactivity, makes them useful substrates for the synthesis of different organophosphorus compounds. The organic synthesis with participations of phosphorylated allenes lead to the formation of five-or six-membered phosphorus heterocycles with certain biological activity (Enchev, 2010).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Cytostatic Activity of 4-bromo-5-ethyl-2-(ethylamino)- 5-methyl-5H-1,2-oxaphosphole 2-oxide

2018

J App Pharm Sci

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Synthesis of phosphorus heterocycles has gained increasing interest in recent years. Here we wish to report our results on synthesis and on studying of biological activity of 4-bromo-5-ethyl-2-(ethylamino)-5-methyl-5H-1,2-oxaphosphole 2-oxide (Br-oxph-1) using in vivo and in vitro approaches. Br-oxph-1 represents a structural analogue of 4-bromo-2-(diethylamino)-5-ethyl-5-methyl-5H-1,2-oxaphosphole 2-oxide (Br-oxph). Root growth inhibition test using Triticum aestivum L. seeds was provided in order to determine general toxicity of Br-oxph-1. The effective concentration that cause 50% of root length as compared to control was determined -8.23 × 10 3 μM. Cytotoxic potential of Br-oxph-1 (8.23 × 10 3 μM) was evaluated using Allium cepa L.-test. Significant decline in mitotic activity and disturbances of cell cycle kinetics were observed. Further, effects of Br-oxph-1 on human hepatoma cell line SK-HEP-1 in vitro were evaluated by means of cell proliferation assay. The results revealed concentration-dependent and statistically significant inhibitory effect. Concentration of Br-oxph-1 showing 50% reduction in cell proliferation/ viability was 0.642 × 10 3 µM. In conclusion, plant test-systems used in this study revealed growth inhibitory and cytostatic effects of Br-oxph-1. Data in vitro was in accordance with these results. Results of present study revealed stronger cytostatic effect of Br-oxph-1 in comparison with Br-oxph. Obviously, modifications in chemical structure of Br-oxph influence its biological effects.

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Synthesis and Biological Activity of 2,5-Dihydro-1,2-Oxaphosphole-2-Oxide Derivatives

Cited by 7 publications

References 77 publications

Synthesis and Anti-Pancreatic Cancer Activity Studies of Novel 3-Amino-2-hydroxybenzofused 2-Phospha-γ-lactones

Synthesis and Anti-Pancreatic Cancer Activity Studies of Novel 3-Amino-2-hydroxybenzofused 2-Phospha-γ-lactones

Interaction of 1,2-alkadienephosphonates with propargyl alcohole

Synthesis and Cytostatic Activity of 4-bromo-5-ethyl-2-(ethylamino)- 5-methyl-5H-1,2-oxaphosphole 2-oxide

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