Design, synthesis and evaluation of novel levoglucosenone derivatives as promising anticancer agents

Tsai, Yi-Hsuan; Etichetti, Carla M. Borini; Cicetti, Soledad; Girardini, Javier E.; Spanevello, Rolando A.; Suárez, Alejandra G.; Sarotti, Ariel M.

doi:10.1016/j.bmcl.2020.127247

Cited by 19 publications

(17 citation statements)

References 26 publications

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“…1,2,3-Triazole-tethered clarithromycinhydroxamic acid hybrid 69 (IC 50 : 23.9 and 2.85 nM) demonstrates excellent inhibitory activity against HDAC1 and HDAC6, and the activity of this hybrid (IC 50 : 0.99 and 0.69 μm, MTT assay) is around five-fold higher than that of SAHA (IC 50 : 5.00 and 3.27 μm) against A549 cells (Tapadar et al, 2015). Some 1,2,3-triazole-containing sugar derivatives also possess certain antiproliferative activity against lung cancer cell lines (Petrova et al, 2015;Jakukowski et al, 2020;Tsai et al, 2020;Zi et al, 2020), and 1,2,3triazole-tethered β-D-ribofuranose-pyridine hybrid 70 (IC 50 : 17.7 μm, MTT assay) is 3.4-fold more potent than cisplatin (IC 50 : 17.7 μm) against A549 cells (Jakukowski et al, 2020), whereas hybrids 71 (IC 50 : 0.18-54.89 μm, MTT assay) are more active than 5-fluorouracil (IC 50 : 69.07 μm) . An SAR study suggests that the electron-donating group benefits the activity compared with the electronwithdrawing group on the phenyl ring, and replacement of the phenyl ring by the pyridinyl ring results in significant loss of activity.…”

Section: Miscellaneous 123-triazole-containing Compoundsmentioning

confidence: 96%

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

Liang

Sun

et al. 2021

Front. Pharmacol.

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Lung cancer is the most common malignancy and leads to around one-quarter of all cancer deaths. Great advances have been achieved in the treatment of lung cancer with novel anticancer agents and improved technology. However, morbidity and mortality rates remain extremely high, calling for an urgent need to develop novel anti–lung cancer agents. 1,2,3-Triazole could be readily interact with diverse enzymes and receptors in organisms through weak interaction. 1,2,3-Triazole can not only be acted as a linker to tether different pharmacophores but also serve as a pharmacophore. This review aims to summarize the recent advances in 1,2,3-triazole–containing compounds with anti–lung cancer potential, and their structure–activity relationship (SAR) together with mechanisms of action is also discussed to pave the way for the further rational development of novel anti–lung cancer candidates.

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Section: Miscellaneous 123-triazole-containing Compoundsmentioning

confidence: 96%

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

Liang

Sun

et al. 2021

Front. Pharmacol.

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“…The phenyl hydroximoyl chlorides (Figure S1 in Supporting Information File 1 ) were synthesized by following literature procedures [ 44 – 45 ]. To a solution of the corresponding benzaldehyde (1 mmol) in a 1:1 EtOH/H 2 O mixture (1 mL) was added sodium acetate (1.1 mmol) and hydroxylamine hydrochloride (1.1 mmol).…”

Section: Methodsmentioning

confidence: 99%

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

Hossain¹,

Khan²,

Kim³

et al. 2022

Beilstein J. Org. Chem.

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Herein we report a method for the synthesis of 3,4,5-trisubstituted isoxazoles in water under mild basic conditions at room temperature via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides. We optimized the reaction conditions to control the selectivity of the production of isoxazoles and circumvent other competing reactions, such as O-imidoylation or hetero [3 + 2]-cycloaddition. The reaction happens fast in water and completes within 1–2 hours, which provides an environmentally friendly access to 3,4,5-trisubstituted isoxazoles, an important class of structures found in numerous bioactive natural products and pharmaceuticals. Additionally, we optimized the reaction conditions to produce trifluoromethyl-substituted isoxazoles, a prevalent scaffold in biomedical research and drug discovery programs. We also proposed a plausible mechanism for the selectivity of the [3 + 2]-cycloaddition reaction to produce 3,4,5-trisubstituted isoxazoles. Not to be overlooked are our optimized reaction conditions for the dimerization of hydroximoyl chlorides to form furoxans also known as 1,2,5-oxadiazole 2-oxides, a class of structures with important biological activities due to their unique electronic nature and coordination ability.

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“…Primary amines have also been shown to be good nucleophiles for addition to the enone functionality of LGO. For example, further work by Sarotti and co-workers showed that the reaction of propargyl amine to LGO in the presence of base gave addition adduct 34 ( Figure 10 ) ( Tsai et al, 2020 ). Testing of this chain extended series on MDA-MB-231 cells, specifically endogenous mutant p53 knock down (R280K), and by reintroducing p53 R280K in cells lacking p53 expression, anti-proliferative activities against lung and colon cancer cell lines were demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Levoglucosenone: Bio-Based Platform for Drug Discovery

Camp¹,

Greatrex

2022

Front. Chem.

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Levoglucosone (LGO) is a bio-privileged molecule that can be produced on scale from waste biomass. This chiral building block has been converted via well-established chemical processes into previously difficult-to-synthesize building blocks such as enantiopure butenolides, dihydropyrans, substituted cyclopropanes, deoxy-sugars and ribonolactones. LGO is an excellent starting material for the synthesis of biologically active compounds, including those which have anti-cancer, anti-microbial or anti-inflammatory activity. This review will cover the conversion of LGO to biologically active compounds as well as provide future research directions related to this platform molecule.

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Design, synthesis and evaluation of novel levoglucosenone derivatives as promising anticancer agents

Cited by 19 publications

References 26 publications

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

Levoglucosenone: Bio-Based Platform for Drug Discovery

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