Easy access to Ugi-derived isatin-peptoids and their potential as small-molecule anticancer agents

Marques, Carolina S.; González-Bakker, Aday; Padrón, José M.; Burke, Anthony J.

doi:10.1039/d2nj03627d

Cited by 6 publications

(13 citation statements)

References 49 publications

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“…Resourcefulness of the Ugi4CR and preliminary SAR studies [16] lead us to synthesize a third library of oxindole-derivatives, using trifluoroacetic acid (TFA), in mild reaction conditions, to afford the corresponding -acetoamide carboxamide isatin hybrids 8 from the 3-protected oxindole counterparts 5 and 7, in moderate to good yields (Scheme 4). The best yield was obtained when 3-protected oxindole derivatives 5 possess an aromatic or heterocyclic unit substituted in the 5-amide position of the oxindole ring.…”

Section: Methodsmentioning

confidence: 99%

“…Underlining sustainability and economically favored processes, a second family of acetoamide carboxamide oxindole derivatives 5 was obtained using the previously optimized Ugi4CR approach [16] (Scheme 2 and Figure 2). Taking into account the preliminary SAR studies reported for the first family of Ugi-derived isatin-peptoids, the second family was obtained using the 5-amino-1-benzyl-3,3-dimethoxyindolin-2-one [12] 1 and the benzyl isocyanide 4, as amine and isocyanide components, respectively.…”

Section: Synthesismentioning

confidence: 99%

“…[6][7] Oxindole framework is a privilege unit, recognized massively by its extensive biological applications. [8][9] In the last few years we have been active in isatin modification using new synthetic approaches, anticipating the creation of new libraries of small-molecule hybrids with potential as cholinesterase 3 inhibitors [10][11][12][13], important to treat neurodegenerative diseases, and anticancer agents [14][15][16] (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…Despite long years of research, there is still an urgent need to find novel, effective and safe drugs for cancer therapy. [10][11][12][13][14][15][16] Recently, focusing on the design of more potent anticancer drug candidates using more sustainable synthetic processes, we report a new Ugi 4-component reaction approach for easy access to Ugi-derived isatin-peptoids in moderate to excellent yields (up to 99% yield). Some selected compounds were screened against five human solid 4 tumor cell lines: lung (A549), breast (HBL-100 and T-47D), cervix (HeLa) and colon (WiDr).…”

Section: Introductionmentioning

confidence: 99%

“…Also, benzyl isocyanide was favored over the aliphatic one (Scheme 1, (A)). [16] Considering the value of amide groups in drug discovery [19], the feasibility of running the isatin-based Ugi reaction [16,[20][21][22][23] and the potential of the bis-amideoxindole type derivatives as anticancer agents, a second family was synthesized, and bio evaluated (Scheme 1, (B)). Scheme 1: (A) Library of isatin-based -acetoamide carboxamide oxindole derivatives obtained using an Ugi four component reaction (Ugi4CR).…”

Section: Introductionmentioning

confidence: 99%

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The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetoamide carboxamide oxindole hybrids

Marques,

González-Bakker,

Padrón

2023

Preprint

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Considering early-stage drug discovery programmes, the Ugi four component reaction is a valuable, flexible, and pivotal tool, facilitating the creation of two new amide bonds in a one-pot fashion to effectively yield the desired a-aminoacyl amides. Here, we highlight the reputation of this reaction approach to access number and scaffold diversity of a library of isatin-based a-acetoamide carboxamide oxindole hybrids, promising anticancer agents, in a mild and fast sustainable reaction process. The library was tested against six human solid tumor cell lines, among them, non-small cell lung carcinoma, cervical adenocarcinoma, breast cancer and colon adenocarcinoma. The most potent compounds 8d, 8h and 8k showed GI50 values in the range of 1-10 uM.

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Section: Methodsmentioning

confidence: 99%

Section: Synthesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetoamide carboxamide oxindole hybrids

Marques,

González-Bakker,

Padrón

2023

Preprint

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The Asymmetric Petasis Borono-Mannich Reaction: Insights on the Last 15 Years

Marques

Brandão

2023

Catalysts

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The Petasis borono-Mannich reaction, commonly described as the Petasis reaction, was one of the latest famous multicomponent reactions described in the literature. Currently celebrating its 30th anniversary since it was first reported by Petasis and Akritopoulou in 1993, this reaction has emerged as a powerful tool for the synthesis of biologically relevant molecules (such as substituted amines or amino acids), among others. This three-component catalyst-free reaction (the classic model), involving the coupling of an aldehyde, an amine, and a boronic acid, enables the synthesis of polysubstituted amine-containing molecules. Several accounts regarding the catalyst-free version using different carbonyl, amine, and boron-type components have been reported thus far. In contrast, the asymmetric version is still in its infancy since it was first reported in 2007. In this work, we aim to review the asymmetric versions of the Petasis reaction reported over the last 15 years, considering the chiral pool approach (asymmetric induction by one reaction component) and the use of catalysts (organocatalysts, transition-metal catalysts, and others) to access enantiomeric and diastereomeric pure amino-derivatives. Insights regarding the catalyzed Petasis reaction and consequent sustainable synthesis will be highlighted.

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Targeting Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2): Latest Insights on Synthetic Strategies

Marques,

Brandão,

Burke

2024

Molecules

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Vascular endothelial growth factor receptor 2 (VEGFR-2) is a crucial mediator of angiogenesis, playing a pivotal role in both normal physiological processes and cancer progression. Tumors harness VEGFR-2 signaling to promote abnormal blood vessel growth, which is a key step in the metastasis process, making it a valuable target for anticancer drug development. While there are VEGFR-2 inhibitors approved for therapeutic use, they face challenges like drug resistance, off-target effects, and adverse side effects, limiting their effectiveness. The quest for new drug candidates with VEGFR-2 inhibitory activity often starts with the selection of key structural motifs present in molecules currently used in clinical practice, expanding the chemical space by generating novel derivatives bearing one or more of these moieties. This review provides an overview of recent advances in the development of novel VEGFR-2 inhibitors, focusing on the synthesis of new drug candidates with promising antiproliferative and VEGFR-2 inhibition activities, organizing them by relevant structural features.

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Easy access to Ugi-derived isatin-peptoids and their potential as small-molecule anticancer agents

Abstract: The amide bond is one of the most important functional motifs in chemistry and biology due to its presence in countless biological structures and is of significant synthetic interest. Small-molecule...

Cited by 6 publications

References 49 publications

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetoamide carboxamide oxindole hybrids

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetoamide carboxamide oxindole hybrids

The Asymmetric Petasis Borono-Mannich Reaction: Insights on the Last 15 Years

Targeting Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2): Latest Insights on Synthetic Strategies

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