Synthesis and Biological Evaluation of 2-(3‘,4‘,5‘-Trimethoxybenzoyl)-3-Amino 5-Aryl Thiophenes as a New Class of Tubulin Inhibitors

Romagnoli, Romeo; Baraldi, Pier Giovanni; Remusat, Vincent; Carriòn, María Dora; Cara, Carlota Lopez; Preti, Delia; Fruttarolo, Francesca; Pavani, Maria Giovanna; Tabrizi, Mojgan Aghazadeh; Tolomeo, Manlio; Grimaudo, Stefania; Balzarini, Jan; Jordan, Mary Ann; Hamel, Ernest

doi:10.1021/jm060804a

Cited by 51 publications

(26 citation statements)

References 20 publications

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“…More and more derivatives have been demonstrated to present obvious antimicrobial, antitumor, antifungal activity, etc. [34][35][36][37][38][39][40][41][42] Hence, as part of our agrochemistry program aimed at the search for novel natural product-oriented bioactive molecules, based on the aforementioned, we utilized blactam scaffold as prototype structural unit and planed for the incorporating natural gallic acid and azetidinone moieties in a single molecular scaffold (Fig. 2).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Activity of a Series of Novel N‐Substituted β‐Lactams Derived from Natural Gallic Acid

Cao

Wang

et al. 2011

J Chinese Chemical Soc

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Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Activity of a Series of Novel N‐Substituted β‐Lactams Derived from Natural Gallic Acid

Cao

Wang

et al. 2011

J Chinese Chemical Soc

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“…The role of halogen substitutions has been extensively discussed in the literature. Different authors have found that K d or IC 50 values improve up to a point in which a further increase in van der Waals radius brings a significant decrease in affinity (4–13). The breaking point occurs at different van der Waals radii (i.e.…”

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confidence: 99%

How Much Binding Affinity Can be Gained by Filling a Cavity?

et al. 2010

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Binding affinity optimization is critical during drug development. Here we evaluate the thermodynamic consequences of filling a binding cavity with functionalities of increasing van der Waals radii (-H, -F, -Cl and CH3) that improve the geometric fit without participating in hydrogen bonding or other specific interactions. We observe a binding affinity increase of two orders of magnitude. There appears to be three phases in the process. The first phase is associated with the formation of stable van der Waals interactions. This phase is characterized by a gain in binding enthalpy and a loss in binding entropy, attributed to a loss of conformational degrees of freedom. For the specific case presented in this paper, the enthalpy gain amounts to −1.5 kcal/mol while the entropic losses amount to +0.9 kcal/mol resulting in a net 3.5-fold affinity gain. The second phase is characterized by simultaneous enthalpic and entropic gains. This phase improves the binding affinity 25-fold. The third phase represents the collapse of the trend and is triggered by the introduction of chemical functionalities larger than the binding cavity itself (CH(CH3)2). It is characterized by large enthalpy and affinity losses. The thermodynamic signatures associated with each phase provide guidelines for lead optimization.

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“…2-Amino-3-(2-benzylidene-6-bromocyclohexylidene)prop-1-ene-1,1,3-tricarbonitrile (7). -A solution of compound 2 (0.30 g, 1 mmol) in glacial acetic acid (30 mL) was warmed to 60 o C, then bromine solution (0.16 g, 1 mmol) in acetic acid (10 mL) was added dropwise under continuous stirring.…”

Section: -(Aminomentioning

confidence: 99%

Use of 2-aminoprop-1-ene-1,1,3-tricarbonitrile for the synthesis of tetrahydronaphthalene, hexahydroisoquinoline and hexahydrocinnoline derivatives with potential antitumor activities

Mohareb¹,

Moustafa²

2011

Acta Pharmaceutica

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Use of 2-aminoprop-1-ene-1,1,3-tricarbonitrile for the synthesis of tetrahydronaphthalene, hexahydroisoquinoline and hexahydrocinnoline derivatives with potential antitumor activities The aim of the work was to synthesize heterocyclic compounds from 2-aminoprop-1-ene-1,1,3-tricarbonitrile and to study their antitumor activities. The title reagent reacted with cyclohexanone to give the ethylidene derivative 2. The reactivity of the latter product towards different chemical reagents was studied to give tetrahydronaphthalene, hexahydroisoquinoline and hexahydrocinnoline derivatives. The newly synthesized products were screened as antitumor agents on the in vitro growth of three human tumor cell lines representing different tumor types, namely, breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268). It was found that some of these compounds showed inhibitory effects on the three cell lines, indicating their potential use in the development of oncology products.

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Synthesis and Biological Evaluation of 2-(3‘,4‘,5‘-Trimethoxybenzoyl)-3-Amino 5-Aryl Thiophenes as a New Class of Tubulin Inhibitors

Cited by 51 publications

References 20 publications

Synthesis and Biological Activity of a Series of Novel N‐Substituted β‐Lactams Derived from Natural Gallic Acid

Synthesis and Biological Activity of a Series of Novel N‐Substituted β‐Lactams Derived from Natural Gallic Acid

How Much Binding Affinity Can be Gained by Filling a Cavity?

Use of 2-aminoprop-1-ene-1,1,3-tricarbonitrile for the synthesis of tetrahydronaphthalene, hexahydroisoquinoline and hexahydrocinnoline derivatives with potential antitumor activities

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