Halogenated naphthochalcones and structurally related naphthopyrazolines with antitumor activity

Schmitt, Florian; Draut, Heidrun; Biersack, Bernhard; Schobert, Rainer

doi:10.1016/j.bmcl.2016.09.076

Cited by 11 publications

(5 citation statements)

References 18 publications

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“…Specially, an external validation set was manually curated from 35 recent publications ( Gallus et al, 2014 ; Gu et al, 2014 ; Shukla et al, 2014 ; Tan et al, 2014 ; Winter et al, 2014 ; Yang et al, 2014 ; Gozzi et al, 2015 ; Koehler and Wiese, 2015 ; Li et al, 2015 ; Marighetti et al, 2015 ; Chen et al, 2016 ; Gupta et al, 2016 ; Kraege et al, 2016a ; Kraege et al, 2016b ; Krapf and Wiese, 2016 ; Li et al, 2016b ; Miyata et al, 2016 ; Pires et al, 2016 ; Reznicek et al, 2016 ; Schmitt et al, 2016 ; Schwarz et al, 2016 ; Song et al, 2016 ; Spindler et al, 2016 ; Gujarati et al, 2017 ; Krapf et al, 2017b ; Krapf et al, 2017a ; Marchitti et al, 2017 ; Montanari et al, 2017 ; Schaefer et al, 2017 ; Sjöstedt et al, 2017 ; Stefan et al, 2017 ; Zhang et al, 2017 ; Koehler et al, 2018 ; Liao et al, 2018 ; Paterna et al, 2018 ). Because experimental assays were performed under different conditions (e.g., concentration of compound and cell models), it was impossible to set up an inhibition threshold for the definition of inhibitors or non-inhibitors.…”

Section: Methodsmentioning

confidence: 99%

Development of Simple and Accurate in Silico Ligand-Based Models for Predicting ABCG2 Inhibition

et al. 2022

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The ATP binding cassette transporter ABCG2 is a physiologically important drug transporter that has a central role in determining the ADMET (absorption, distribution, metabolism, elimination, and toxicity) profile of therapeutics, and contributes to multidrug resistance. Thus, development of predictive in silico models for the identification of ABCG2 inhibitors is of great interest in the early stage of drug discovery. In this work, by exploiting a large public dataset, a number of ligand-based classification models were developed using partial least squares-discriminant analysis (PLS-DA) with molecular interaction field- and fingerprint-based structural description methods, regarding physicochemical and fragmental properties related to ABCG2 inhibition. An in-house dataset compiled from recently experimental studies was used to rigorously validated the model performance. The key molecular properties and fragments favored to inhibitor binding were discussed in detail, which was further explored by docking simulations. A highly informative chemical property was identified as the principal determinant of ABCG2 inhibition, which was utilized to derive a simple rule that had a strong capability for differentiating inhibitors from non-inhibitors. Furthermore, the incorporation of the rule into the best PLS-DA model significantly improved the classification performance, particularly achieving a high prediction accuracy on the independent in-house set. The integrative model is simple and accurate, which could be applied to the evaluation of drug-transporter interactions in drug development. Also, the dominant molecular features derived from the models may help medicinal chemists in the molecular design of novel inhibitors to circumvent ABCG2-mediated drug resistance.

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Section: Methodsmentioning

confidence: 99%

Development of Simple and Accurate in Silico Ligand-Based Models for Predicting ABCG2 Inhibition

et al. 2022

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“…The halogenated chalcones 14 a‐d and its derivative pyrazolines 14 e – g (Figure 3) were synthesized by Schmitt et al . and their antitumor activities were also studied by MTT assay [57] . The tests on various cancer cell lines revealed that chalcones had lower single‐digit IC 50 values than pyrazolines, while pyrazolines had lower double‐digit IC 50 values (5–10 μM).…”

Section: Pharmacological Activitymentioning

confidence: 99%

Naphthyl‐Based Chalcone Derivatives: A Multifaceted Player in Medicinal Chemistry

Mahesha,

Shetty

2024

ChemistrySelect

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Research has placed a great deal of emphasis on molecule development and discovery with substantial biological profiling in recent years. Despite the significant side effects, medicinal chemists have long strived to synthesize drug molecules with the highest level of therapeutic activity and the lowest possible level of toxicity. The naphthyl‐based chalcone derivatives have drawn attention due to their simple structures and wide range of pharmacological effects. The main focus of this review is to outline the biologically active molecules based on naphthyl moiety‐substituted chalcone derivatives developed over the years. A synopsis of pharmacological screening, including relevant structure‐activity relationships, action mechanisms, and possible therapeutic applications, is provided in this article. It is true that prospective hybrids combining the naphthyl moiety with different chalcone pharmacophores are needed to address drug resistance and improve specificity. Therefore, this review may be useful in the development and design of new, highly successful therapeutic drugs based on previously reported methodologies.

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“…Both synthetic (compounds 124 and 125 ) and natural chalcones (compounds 1–14 ) bearing hydroxyl functional groups demonstrate higher activity in breast cancer cell lines [ 257 , 258 ]. Similarly, halogenated synthetic chalcones and methoxylated chalcones derived from both natural and synthetic sources have proven to be highly active against liver, prostrate, and lung cancer cell lines [ 259 , 260 , 261 , 262 ]. In addition, trihydroxylated and methoxylated chalcones showed higher activity than di- and mono-substituted ones [ 263 , 264 , 265 ].…”

Section: Sar Studiesmentioning

confidence: 99%

Chalcone: A Promising Bioactive Scaffold in Medicinal Chemistry

et al. 2022

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Chalcones are a class of privileged scaffolds with high medicinal significance due to the presence of an α,β-unsaturated ketone functionality. Numerous functional modifications of chalcones have been reported, along with their pharmacological behavior. The present review aims to summarize the structures from natural sources, synthesis methods, biological characteristics against infectious and non-infectious diseases, and uses of chalcones over the past decade, and their structure–activity relationship studies are detailed in depth. This critical review provides guidelines for the future design and synthesis of various chalcones. In addition, this could be highly supportive for medicinal chemists to develop more promising candidates for various infectious and non-infectious diseases.

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Halogenated naphthochalcones and structurally related naphthopyrazolines with antitumor activity

Cited by 11 publications

References 18 publications

Development of Simple and Accurate in Silico Ligand-Based Models for Predicting ABCG2 Inhibition

Development of Simple and Accurate in Silico Ligand-Based Models for Predicting ABCG2 Inhibition

Naphthyl‐Based Chalcone Derivatives: A Multifaceted Player in Medicinal Chemistry

Chalcone: A Promising Bioactive Scaffold in Medicinal Chemistry

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