Solid-Phase Parallel Synthesis of Drug-Like Artificial 2H-Benzopyran Libraries

Lee, Tae‐Ho; Gong, Young‐Dae

doi:10.3390/molecules17055467

Cited by 28 publications

(12 citation statements)

References 137 publications

(188 reference statements)

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“…The chromone carboxamide derivatives from series I (3-10, Table 1) were obtained by the condensation of chromone-2-carboxylic acid (1) with the appropriate amine (Scheme 1) using the coupling reagent PyBOP in the presence of DIPEA (353637). Chromane-2,4-dione derivatives from series II (11-18, Table 1) were obtained with similar reaction conditions by using chromone-3-carboxylic acid (2) as starting material (Scheme 1). As it was previously reported (13), the high reactivity at C-2 position of the ester intermediate formed in situ between the carboxylic acid and PyBOP, changed the course of the reaction resulting in a nucleophilic attack by the (hetero) aromatic amine at C-2 position of the benzopyran ring.…”

Section: Resultsmentioning

confidence: 99%

“…Benzopyrone-based compounds, such as chromone, coumarin, and flavonoids have come to the attention of many investigators in recent years, due to their distinctive chemical and biological properties (1234). In this context, benzopyran and its derivatives constitute an important class of natural compounds representing a broad range of biological activities such as antibacterial and antiviral (56), anticancer (78), antioxidant (59), anti-inflammatory (10), monoamine oxidase B inhibition (111213), interaction with A3 adenosine receptor (1415), and anticoagulant effects (16).…”

Section: Introductionmentioning

confidence: 99%

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Searching for new cytotoxic agents based on chromen-4-one and chromane-2,4-dione scaffolds

et al. 2019

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Cancer is a major cause of death worldwide and novel anticancer agents for its better management are much needed. Benzopyrone-based compounds, such as chromones, possess several distinctive chemical and biological properties, of which the cytotoxicity against cancer cells seems to be prominent. In this study, two series of compounds based on chromen-4-one (3-10) and chromane-2,4-dione (11-18) scaffolds were synthesized in moderate/high yields and evaluated for cytotoxicity against HL-60, MOLT-4, and MCF-7 cancer cells using MTT assay. In general, the compounds exhibited moderate cytotoxic effects against the cancer cell lines, among which, a superior potency could be observed against MOLT-4 cells. Chroman-2,4-dione (11-18) derivatives had overall higher potencies compared to their chromen-4-one (3-10) counterparts. Compound 13 displayed the lowest IC 50 values against HL-60 (IC 50 , 42.0 ± 2.7 μM) and MOLT-4 cell lines (IC 50 , 24.4 ± 2.6 μM), while derivative 11 showed the highest activity against MCF-7 cells (IC 50 , 68.4 ± 3.9 μM). In conclusion, this study provides important information on the cytotoxic effects of chromone derivatives. Benzochroman-2,4-dione has been identified as a promising scaffold, which its potency can be modulated by tailored synthesis with the aim of finding novel and dissimilar anticancer compounds.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Searching for new cytotoxic agents based on chromen-4-one and chromane-2,4-dione scaffolds

et al. 2019

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“…As shown in Figure 3A , the chemical structure of Compound 12 shows that it is a benzopyranyl 1,2,3-triazole. This compound was synthesized by Cu(I)-catalyzed [3 + 2] cycloaddition of 2-(azidomethyl)-2-methyl-6-nitro-2 H -chromene and 1-ethynyl-4-methoxybenzene [ 15 , 16 ]. Compound 12 has a benzopyran scaffold structure that is novel when compared to the chemical structures of known HIF-1α inhibitors, such as YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] [ 17 ], topotecan ( S )-10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1 H -pyrano[3′,4′:6,7]indolizino[1,2- b ]quinoline-3,14(4 H ,12 H )-dione monohydrochloride [ 18 ], echinomycin [ 19 ], and manassantin [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

Molecular and functional evaluation of a novel HIF inhibitor, benzopyranyl 1,2,3-triazole compound

Park

Lee

et al. 2016

Oncotarget

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Hypoxia occurs in a variety of pathological events, including the formation of solid tumors. Hypoxia-inducible factor (HIF)-1α is stabilized under hypoxic conditions and is a key molecule in tumor growth and angiogenesis. Seeking to develop novel cancer therapeutics, we investigated small molecules from our in-house chemical libraries to target HIF-1α. We employed a dual-luciferase assay that uses a luciferase (Luc) reporter vector harboring five copies of hypoxia-responsive element (HRE) in the promoter. Under hypoxic conditions that increased Luc reporter activity by four-fold, we screened 144 different compounds, nine of which showed 30–50% inhibition of hypoxia-induced Luc reporter activity. Among these, “Compound 12, a benzopyranyl 1,2,3-triazole” was the most efficient at inhibiting the expression of HIF-1α under hypoxic conditions, reducing its expression by 80%. Under hypoxic conditions, the half maximal IC50 of the compound was 24 nM in HEK-293 human embryonic kidney cells, and 2 nM in A549 human lung carcinoma cells. Under hypoxic conditions, Compound 12 increased hydroxylated HIF-1α levels and HIF-1α ubiquitination, and also dose-dependently decreased HIF-1α target gene expression as well as vascular endothelial growth factor (VEGF) secretion. Furthermore, this compound inhibited VEGF-induced in vitro angiogenesis in human umbilical vein endothelial cells (HUVECs), and in vivo, it inhibited chick chorioallantoic membrane angiogenesis. In allogaft assays, cotreatment with Compound 12 and gefitinib significantly inhibited tumor growth and angiogenesis. Compound 12 can be a novel inhibitor of HIF-1α by accelerating its degradation, and shows much potential as an anti-cancer agent through its ability to suppress tumor growth and angiogenesis.

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“…[12][13][14] Considerable work has been carried out on this class of compounds and the benzopyrans and their bioactivities have been recently reviewed. 15 This body of work demonstrates how simple modifications of such privileged structures can lead to novel potential agents.…”

Section: Benzopyrans Unusual Antibacterial and Other Agentsmentioning

confidence: 99%

Making Sense of Structures by Utilizing Mother Nature's Chemical Libraries as Leads to Potential Drugs

Newman¹,

Cragg²

2014

Natural Products

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Solid-Phase Parallel Synthesis of Drug-Like Artificial 2H-Benzopyran Libraries

Cited by 28 publications

References 137 publications

Searching for new cytotoxic agents based on chromen-4-one and chromane-2,4-dione scaffolds

Searching for new cytotoxic agents based on chromen-4-one and chromane-2,4-dione scaffolds

Molecular and functional evaluation of a novel HIF inhibitor, benzopyranyl 1,2,3-triazole compound

Making Sense of Structures by Utilizing Mother Nature's Chemical Libraries as Leads to Potential Drugs

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