A methanol and protic ionic liquid Ugi multicomponent reaction path to cytotoxic α-phenylacetamido amides

Otaibi, Ahmed Al; Deane, Fiona M.; Russell, Cecilia C.; Hizartzidis, Lacey; McCluskey, Siobhann N.; Sakoff, Jennette A.; McCluskey, Adam

doi:10.1039/c9ra00118b

Cited by 9 publications

(14 citation statements)

References 53 publications

(81 reference statements)

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“…Biologically active α-amino amide analogs (RS)-N-(2-(Cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylpropiolamide (α-AAA-A) and (RS)-N-(2-(Cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylbut2-enamide (α-AAA-B) were synthesized using linear Ugi multicomponent reaction (batch reaction with methanol) as published previously ( 12 ). Briefly, for the synthesis of α-AAA-A, a solution was prepared using methanol (5 ml), aniline (0.09 ml; 1 mmol) and benzaldehyde (0.1 ml; 1 mmol).…”

Section: Methodsmentioning

confidence: 99%

“…Some important molecules, such as Brentuximab Vedotin, Gemtuzumab Ozogamicin, Ado-trastuzumab emtansine, polatuzumab vedotin-piiq, and inotuzumab ozogamicin, are combined with monoclonal antibodies specific to surface antigens present on particular tumor cells and are used as combinationaltargeted cancer therapies (11). There are a number of newly synthesized a-amino amide derivatives, which show potent anticancer and cytotoxic activities against a wide range of cancer cell lines (12). Derivatives of 3-cyano pyridine also exhibited cytotoxic activities against many human MCF-7, HCT-116, and HepG-2 cancer cell lines (13).…”

Section: Introductionmentioning

confidence: 99%

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Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia

et al. 2021

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Advanced stage cancers are aggressive and difficult to treat with mono-therapeutics, substantially decreasing patient survival rates. Hence, there is an urgent need to develop unique therapeutic approaches to treat cancer with superior potency and efficacy. This study investigates a new approach to develop a potent combinational therapy to treat advanced stage leukemia. Biologically active α-amino amide analogs (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylpropiolamide (α-AAA-A) and (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylbut2-enamide (α-AAA-B) were synthesized using linear Ugi multicomponent reaction. Cytotoxicities and IC50 values of α-AAA-A and α-AAA-B against leukemia cancer cell lines (HL-60 and K562) were analyzed though MTT assay. Cytotoxic assay analyzed percent killing of leukemia cell lines due to the effect of γδ T cells alone or in combination with α-AAA-A or α-AAA-B. Synthesized biologically active molecule α-AAA-A exhibited increased cytotoxicity of HL-60 (54%) and K562 (44%) compared with α-AAA-B (44% and 36% respectively). Similarly, α-AAA-A showed low IC50 values for HL-60 (1.61 ± 0.11 μM) and K562 (3.01 ± 0.14 μM) compared to α-AAA-B (3.12 ± 0.15 μM and 6.21 ± 0.17 μM respectively). Additive effect of amide analogs and γδ T cells showed significantly high leukemia cancer cell killing as compared to γδ T cells alone. A unique combinational therapy with γδ T cells and biologically active anti-cancer molecules (α-AAA-A/B), concomitantly may be a promising cancer therapy.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia

et al. 2021

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“…For our system, gelation only occurred at 60 °C. It is known that at higher temperatures, the reaction yield is increased granting faster connectivity of the network [18,29] …”

Section: Figurementioning

confidence: 99%

“…It is known that at higher temperatures, the reaction yield is increased granting faster connectivity of the network. [18,29] The aldehyde and the isocyanide are very important components for the Ugi reaction. The poor choice of the aldehyde can lead to a low concentration of the iminium ion, which is critical to yield the Ugi scaffold because, without the nucleophilic attack of the isocyanide to the iminium ion, the scaffold is not formed.…”

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confidence: 99%

Versatile and Tunable Poly(Ethylene Glycol)‐Based Hydrogels Crosslinked through the Ugi Reaction

et al. 2020

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The four‐component Ugi condensation reaction has been investigated to assemble chemically crosslinked hydrogels using multivalent star‐shaped poly(ethylene glycol) components. The resulting biocompatible hydrogels are highly versatile in composition and function. It is shown that acid, aldehyde, and cyanide components can be varied yielding materials with precise structure and tunable stiffness. Additionally, the resulting hydrogels were proven extremely robust to consecutive drying‐swelling cycles. This property was explored to develop a reversible humidity colorimetric sensor gel. Overall, this work demonstrates the application of the four‐component Ugi reaction as a powerful tool to quickly generate crosslinked gels with precise control in chemical composition.

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“…These extensive applications of ILs are attributed to their unique properties including, low vapor pressure, non-flammability, wide liquid-state temperature range, high thermal and chemical stability, favorable solvating capability, large electrochemical window, and ability to catalyze different kinds of organic reactions. In particular, acidic ILs possess useful characteristics of solid acids and mineral liquid acids, and have been designed to replace conventional mineral liquid acids like sulfuric acid and hydrochloric acid to catalyze chemical transformations [1][2][3][4][5][6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Pourkazemi

Nasouri

Fakhraie

et al. 2020

Asian J. Nanosci. Mater.

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In this study, acidic ionic liquid N, N-diethyl-N-sulfoethanaminium hydrogen sulfate {[Et3N-SO3H]HSO4} was utilized to promote two classes of useful organic transformations under solvent-free conditions including, i) the condensation of arylaldehydes with malononitrile and 1-naphthol, leading to 2-amino-4H-chromenes, and ii) the condensation reaction of arylaldehydes with 2-naphthol to give 14-aryl-14H-dibenzo[a, j]xanthenes. The ionic liquid efficiently catalyzed the reactions, and the products were obtained in excellent yields (94-98%) within short reaction times (8-30 min).

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A methanol and protic ionic liquid Ugi multicomponent reaction path to cytotoxic α-phenylacetamido amides

Abstract: The Ugi reaction (aldehyde, amine, isocyanide and an ethanoic acid) in the protic ionic liquids ethylammonium nitrate (EAN) and propylammonium nitrate (PAN) gave excellent yields of α-phenylacetamido amides.

Cited by 9 publications

References 53 publications

Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia

Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia

Versatile and Tunable Poly(Ethylene Glycol)‐Based Hydrogels Crosslinked through the Ugi Reaction

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