Design, synthesis, and biological evaluation of selenium-containing small molecule compounds based on the dual mechanism of fungal CYP51 inhibition and fungal ROS generation

Guo, Mengbi; Xu, Hui; Yan, Zhong-zuo; Wang, Xin; X, Su; Guo, Chun; Hou, Zhuang; Gong, Ping

doi:10.1016/j.molstruc.2022.133859

Cited by 4 publications

(4 citation statements)

References 20 publications

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“…This can be observed in the different analogues of miconazole. Compound 12 has proven to inhibit CYP51 as the unmodified drug, whereas other derivatives (e.g., 24 – 26 ) exhibit a novel mechanism of action by inducing the formation of ROS. , Despite advances in the study of the mechanisms involved in the bioactivity of a wide range of selenocompounds, it is still difficult to predict how they are going to exert their activities. In 2018, a study unveiled a novel and unexplored programmed cell death mechanism for Se compounds, as two new methylselenoesters provoked entosis in Panc-1 cells as a result of inducing cell detachment by downregulating CDC42 and CD29 .…”

Section: Discussionmentioning

confidence: 99%

“…It is worth mentioning that a great variety of studies have indicated the role of Se-miconazole analogues in different strains of pathogenic fungi. ,, Herein, we compile extensive literature evidence with a description and discussion of the latest advances in this field. The chemical structures of the most representative miconazole derivatives are illustrated in Figure .…”

Section: Selenized Small Molecule Drugsmentioning

confidence: 99%

“…Results after the experiment unveiled the high stability of this analogue, with a half-life value >360 min. 97 Although further studies are needed to establish the efficacy and safety profile of Se analogues, these preliminary studies prove that an optimal introduction of Se functional groups in the structure of miconazole and fluconazole can enhance the antifungal properties of the parent drug. Particularly encouraging is the enhanced activity of certain Se-analogues against corresponding drug-resistant fungal infections, which if successfully developed could address an unmet medical need.…”

Section: Miconazolementioning

confidence: 99%

“…To gain further insight into the druggability of 25 , its plasma stability was determined in an in vitro rat plasma stability assay. Results after the experiment unveiled the high stability of this analogue, with a half-life value >360 min …”

Section: Selenized Small Molecule Drugsmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%