Dataset Information

Recent Advances in the Development of Sigma Receptor Ligands as Cytotoxic Agents: A Medicinal Chemistry Perspective.

ABSTRACT: Since their discovery as distinct receptor proteins, the specific physiopathological role of sigma receptors (σRs) has been deeply investigated. It has been reported that these proteins, classified into two subtypes indicated as σ₁ and σ₂, might play a pivotal role in cancer growth, cell proliferation, and tumor aggressiveness. As a result, the development of selective σR ligands with potential antitumor properties attracted significant attention as an emerging theme in cancer research. This perspective deals with the recent advances of σR ligands as novel cytotoxic agents, covering articles published between 2010 and 2020. An up-to-date description of the medicinal chemistry of selective σ₁R and σ₂R ligands with antiproliferative and cytotoxic activities has been provided, including major pharmacophore models and comprehensive structure-activity relationships for each main class of σR ligands.

SUBMITTER: Fallica AN

PROVIDER: S-EPMC8279423 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Recent Advances in the Development of Sigma Receptor Ligands as Cytotoxic Agents: A Medicinal Chemistry Perspective.

Fallica Antonino N AN Pittalà Valeria V Modica Maria N MN Salerno Loredana L Romeo Giuseppe G Marrazzo Agostino A Helal Mohamed A MA Intagliata Sebastiano S

Journal of medicinal chemistry 20210602 12

Since their discovery as distinct receptor proteins, the specific physiopathological role of sigma receptors (σRs) has been deeply investigated. It has been reported that these proteins, classified into two subtypes indicated as σ<sub>1</sub> and σ<sub>2</sub>, might play a pivotal role in cancer growth, cell proliferation, and tumor aggressiveness. As a result, the development of selective σR ligands with potential antitumor properties attracted significant attention as an emerging theme in can ...[more]

PMID: 34076441

Similar Datasets

Project description:The eight contributions here provide ample evidence that shape as a volume or as a surface is a vibrant and useful concept when applied to drug discovery. It provides a reliable scaffold for "decoration" with chemical intuition (or bias) for virtual screening and lead optimization but also has its unadorned uses, as in library design, ligand fitting, pose prediction, or active site description. Computing power has facilitated this evolution by allowing shape to be handled precisely without the need to reduce down to point descriptors or approximate metrics, and the diversity of resultant applications argues for this being an important step forward. Certainly, it is encouraging that as computation has enabled our intuition, molecular shape has consistently surprised us in its usefulness and adaptability. The first Aurelius question, "What is the essence of a thing?", seems well answered, however, the third, "What do molecules do?", only partly so. Are the topics covered here exhaustive, or is there more to come? To date, there has been little published on the use of the volumetric definition of shape described here as a QSAR variable, for instance, in the prediction or classification of activity, although other shape definitions have been successful applied, for instance, as embodied in the Compass program described above in "Shape from Surfaces". Crystal packing is a phenomenon much desired to be understood. Although powerful models have been applied to the problem, to what degree is this dominated purely by the shape of a molecule? The shape comparison described here is typically of a global nature, and yet some importance must surely be placed on partial shape matching, just as the substructure matching of chemical graphs has proved useful. The approach of using surfaces, as described here, offers some flavor of this, as does the use of metrics that penalize volume mismatch less than the Tanimoto, e.g., Tversky measures. As yet, there is little to go on as to how useful a paradigm this will be because there is less software and fewer concrete results.Finally, the distance between molecular shapes, or between any shapes defined as volumes or surfaces, is a metric property in the mathematical sense of the word. As yet, there has been little, if any, application of this observation. We cannot know what new application to the design and discovery of pharmaceuticals may yet arise from the simple concept of molecular shape, but it is fair to say that the progress so far is impressive.

Dataset Information

Recent Advances in the Development of Sigma Receptor Ligands as Cytotoxic Agents: A Medicinal Chemistry Perspective.

Publications

Recent Advances in the Development of Sigma Receptor Ligands as Cytotoxic Agents: A Medicinal Chemistry Perspective.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets