Investigation of chalcogen bioisosteric replacement in a series of heterocyclic inhibitors of tryptophan 2,3-dioxygenase

Kozlova, Arina; Thabault, Léopold; Dauguet, Nicolas; Deskeuvre, Marine; Stroobant, Vincent; Pilotte, Luc; Liberelle, Maxime; Eynde, Benoı̂t Van den; Frédérick, Raphaël

doi:10.1016/j.ejmech.2021.113892

Cited by 11 publications

(8 citation statements)

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“…23 Chalcogen bonding has also been shown to stabilize biological motifs in proteins and chalcogen interactions are also being studied in the field of drug design. 11,24,25 In chemistry and material sciences, chalcogen bonds are reported, among others, in the fields of organocatalysis, [26][27][28][29] anion recognition, optoelectronics, [30][31][32] or supramolecular chemistry. 9,[33][34][35][36][37] Intermolecular interactions between (heavy) chalcogens, have long been known as 'secondary bonding interactions', a term originally coined by Alcock.…”

Section: Paper Synthesismentioning

confidence: 99%

Crystal Structures of Organoselenium Compounds: Structural Descriptors for Chalcogen Bonds

Bodart

Wouters

2022

Synthesis

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Less conventional non-covalent interactions such as chalcogen bonds attract the attention of researchers in various fields (organocatalysis, material sciences, biological chemistry, …). We present here useful descriptors to easily discriminate the structures in which chalcogen bonds involving selenium are observed. Our study focused on organoselenium compounds as chalcogen bond donors and on molecular entities, as chalcogen bond acceptors, containing N, O, S, Se and Te atoms or aromatic rings. For conventional chalcogen bonds (C-Se⋯X, with X = N, O, S, Se, or Te), the combination of the C-Se⋯X angle and the distance between X and the C-Se-C plane proved to be most relevant for identification of chalcogen bonds. For chalcogen⋯π bonds, the most relevant parameters are a combination of the C-Se⋯X angle and the angle between the C-Se bond and the normal to the aromatic ring plane.

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Section: Paper Synthesismentioning

confidence: 99%

Crystal Structures of Organoselenium Compounds: Structural Descriptors for Chalcogen Bonds

Bodart

Wouters

2022

Synthesis

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“…Isosteric replacement is a common strategy in drug design to modulate the physicochemical properties of potential inhibitors. In 2021, Kozlova and co-workers (Kozlova et al, 2021a) highlighted a series of bioisosteric derivatives acting as potential new inhibitors of the protein hTDO2, a therapeutic target in cancer research. These new molecules differ in the replacement of the central atom of benzotriazole by an oxygen, sulfur or selenium atom (Fig.…”

Section: Chemical Contextmentioning

confidence: 99%

“…The synthesis of the various compounds was reported by Kozlova et al (2021a). Crystallization of the 5-(1H-indol-3-yl)benzotriazole derivatives were carried out by the solvent evaporation method.…”

Section: Synthesis and Crystallizationmentioning

confidence: 99%

Structural study of bioisosteric derivatives of 5-(1H-indol-3-yl)-benzotriazole and their ability to form chalcogen bonds

Mirgaux¹,

Scaillet²,

Kozlova³

et al. 2022

Acta Cryst E

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Recently, interest in the isosteric replacement of a nitrogen atom to selenium, sulfur or oxygen atoms has been highlighted in the design of potential inhibitors for cancer research. In this context, the structures of 5-(1H-indol-3-yl)-2,1,3-benzotriazole derivatives [5-(1H-indol-3-yl)-2,1,3-benzothiadiazole (bS, C14H9N3S) and 5-(1H-indol-3-yl)-2,1,3-benzoxadiazole (bO, C14H9N3O)], as well as a synthesis intermediate of the selenated bioisostere [5-[1-(benzensulfonyl)-1H-indol-3-yl]-2,1,3-benzoselenadiazole (p-bSe, C20H13N3O2SSe)] were determined using single-crystal X-ray diffraction (SCXRD) analyses. Despite being analogues, different crystal packing, torsion angles and supramolecular features were observed, depending on the substitution of the central atoms of the benzotriazole. In particular, chalcogen interactions were described in the case of p-bSe and not in the bS and bO derivatives. An investigation by ab initio computational methods was therefore conducted to understand the effect of the substitution on the ability to form chalcogen bonds and the flexibility of the compounds.

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“…Nowadays, the interest in developing innovative clinical alternatives for a large variety of illnesses has experienced an upsurge. Despite state-of-the-art treatments, their use is usually hampered by detrimental adverse effects, drug resistance, reduced treatment adherence, or decreased quality of life for patients. − In this context, a large variety of studies have been carried out to ascertain the possible clinical application of a great variety of organoselenium compounds, as it has been reported that the inclusion of Se motifs into a wide range of active compounds endows them with enhanced physicochemical and biological properties. − Studies regarding chalcogen isosteric replacements have gained great interest throughout the years as they are a feasible option for obtaining distinctive, safer, and more effective drug candidates with improved biopharmacological profiles compared to the parent compounds. − Although chalcogens display similar physicochemical properties, they exhibit different chemical reactivity, mainly related to their acidity, redox potentials, electrophilicity, and nucleophilicity. These differences can be explained mainly by the bigger size and greater polarizability of the Se atom compared with sulfur (S) .…”

Section: Introductionmentioning

confidence: 99%

Selenization of Small Molecule Drugs: A New Player on the Board

Morán-Serradilla,

Plano,

Sanmartín

et al. 2024

J. Med. Chem.

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There is an urgent need to develop safer and more effective modalities for the treatment of a wide range of pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Throughout the years, selenium (Se) has attracted a great deal of attention due to its important role in human health. Besides, a growing body of work has unveiled that the inclusion of Se motifs into a great number of molecules is a promising strategy for obtaining novel therapeutic agents. In the current Perspective, we have gathered the most recent literature related to the incorporation of different Se moieties into the scaffolds of a wide range of known drugs and their feasible pharmaceutical applications. In addition, we highlight different representative examples as well as provide our perspective on Se drugs and the possible future directions, promises, opportunities, and challenges of this ground-breaking area of research. ■ SIGNIFICANCE • Significance: The development of novel compounds for the treatment of numerous pathologies has become a priority due to the lack of effective therapeutic options. • Impact: This work highlights the potential of incorporating Se moieties into the scaffold of several drugs to develop novel safer bioactive compounds. • Innovation: This Perspective discusses the development of selenoderivatives of a wide array of drugs and their biological applications and proposes novel avenues to continue exploring this outstanding research area.

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Investigation of chalcogen bioisosteric replacement in a series of heterocyclic inhibitors of tryptophan 2,3-dioxygenase

Cited by 11 publications

References 50 publications

Crystal Structures of Organoselenium Compounds: Structural Descriptors for Chalcogen Bonds

Crystal Structures of Organoselenium Compounds: Structural Descriptors for Chalcogen Bonds

Structural study of bioisosteric derivatives of 5-(1H-indol-3-yl)-benzotriazole and their ability to form chalcogen bonds

Selenization of Small Molecule Drugs: A New Player on the Board

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