Exploring the chemical space and the bioactivity profile of lactams: a chemoinformatic study

Saldívar-González, Fernanda I.; Lenci, Elena; Trabocchi, Andrea; Medina-Franco, José L.

doi:10.1039/c9ra04841c

Cited by 55 publications

(36 citation statements)

References 46 publications

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“…In fact, compounds 12 and 27 share the same γ -lactam unit with both natural staurosporine and synthetic midostaurine. Although this pharmacophore is becoming increasingly more studied [ 40 ], little is known about the properties of γ-spiro-1-lactams, which are extremely rare in the literature. The same relates to their mechanism of interaction with cellular targets [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

Preparation of Antiproliferative Terpene-Alkaloid Hybrids by Free Radical-Mediated Modification of ent-Kauranic Derivatives

et al. 2021

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A convenient strategy for molecular editing of available ent-kauranic natural scaffolds has been developed based on radical mediated C–C bond formation. Iodine atom transfer radical addition (ATRA) followed by rapid ionic elimination and radical azidoalkylation were investigated. Both reactions involve radical addition to the exo-methylenic double bond of the parent substrate. Easy transformations of the obtained adducts lead to extended diterpenes of broad structural diversity and artificial diterpene-alkaloid hybrids possessing lactam and pyrrolidine pharmacophores. The cytotoxicity of selected diterpenic derivatives was examined by in vitro testing on several tumor cell lines. The terpene-alkaloid hybrids containing N-heterocycles with unprecedented spiro-junction have shown relevant cytotoxicity and promising selectivity indexes. These results represent a solid basis for following research on the synthesis of such derivatives based on available natural product templates.

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Section: Resultsmentioning

confidence: 99%

Preparation of Antiproliferative Terpene-Alkaloid Hybrids by Free Radical-Mediated Modification of ent-Kauranic Derivatives

et al. 2021

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“…Different methods are suitable for this task and a lot of them have been already used to analyze libraries of compounds of natural origin 25 . Principal component analysis (PCA) 26 and scaffold trees 27 were most often used, but self-organizing maps 28 and generative topographic mapping (GTM) 29 were also applied. Most of the numerous articles in this field simply report static results of particular compound library analysis, not allowing readers to explore the chemical space of NPs by themselves.…”

Section: Introductionmentioning

confidence: 99%

NP Navigator: a New Look at the Natural Product Chemical Space

Zabolotna¹,

Ertl²,

Horvath³

et al. 2021

Preprint

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NP Navigator – a freely available intuitive online tool for visualization and navigation through the chemical space of NPs and NP-like molecules. It is based on the hierarchical ensemble of generative topographic maps, featuring NPs from the COlleCtion of Open NatUral producTs (COCONUT), bioactive compounds from ChEMBL and commercially available molecules from ZINC. NP Navigator allows to efficiently analyze different aspects of NPs - chemotype distribution, physicochemical properties, biological activity and commercial availability of NPs. The latter concerns not only purchasable NPs but also their close analogs that can be considered as synthetic mimetics of NPs or pseudo-NPs.<br>

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“…This method, however, did not allow obtaining 1,6‐dihydropyridine‐2(3 H )‐ones unsubstituted at the nitrogen atom. NH ‐δ‐Lactam is an important pharmacophoric moiety [15] capable of forming a dual hydrogen bond donor/acceptor interaction with the protein target [16] . Moreover, the hydrogen bonding of NH ‐lactams in general was recently emphasized as an important control element in transition metal‐catalyzed and photochemical reactions [17] .…”

Section: Introductionmentioning

confidence: 99%

Three‐Component Castagnoli‐Cushman Reaction of 3‐Arylglutaconic Acid Anhydrides, Carbonyl Compounds, and Ammonium Acetate: a Quick and Flexible Way to Assemble Polysubstituted NH‐δ‐lactams

et al. 2021

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A practical straightforward synthesis of medicinally important NH‐δ‐lactams through the three‐component Castagnoli‐Cushman reaction of 3‐arylglutaconic anhydrides with carbonyl compound and ammonium acetate has been developed. The scope of the protocol has been thoroughly explored paying particular attention to the carbonyl component using wide array of aliphatic and aromatic aldehydes as well as rarely involved cyclic and acyclic ketones. Synthetic potential of prepared compounds was demonstrated by a series of post‐modifications, including unexpected isomerization.

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Exploring the chemical space and the bioactivity profile of lactams: a chemoinformatic study

Abstract: Lactams are a class of compounds important for drug design, due to their great variety of potential therapeutic applications, spanning cancer, diabetes, and infectious diseases.

Cited by 55 publications

References 46 publications

Preparation of Antiproliferative Terpene-Alkaloid Hybrids by Free Radical-Mediated Modification of ent-Kauranic Derivatives

Preparation of Antiproliferative Terpene-Alkaloid Hybrids by Free Radical-Mediated Modification of ent-Kauranic Derivatives

NP Navigator: a New Look at the Natural Product Chemical Space

Three‐Component Castagnoli‐Cushman Reaction of 3‐Arylglutaconic Acid Anhydrides, Carbonyl Compounds, and Ammonium Acetate: a Quick and Flexible Way to Assemble Polysubstituted NH‐δ‐lactams

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