Discovery of 1,2,3-selenadiazole analogues as antifungal agents using a scaffold hopping approach

Xu, Hui; Cao, Chun Xia; Wang, Xin; Guo, Mengbi; Yan, Zhong-zuo; An, Ran; Zhang, Rui; Dong, En-hui; Mou, Yanhua; Hou, Zhuang; Guo, Chun

doi:10.1016/j.bioorg.2021.105182

Cited by 13 publications

(13 citation statements)

References 28 publications

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“…Furthermore, the selenoderivatives 1 and 2 of fluconazole displayed similar cytotoxic properties compared to the unmodified drug . Conversely, the replacement of its central scaffold with a 1,2,3-selenadiazole ring furnished compounds with an improved antifungal activity . Besides, the replacement of the oxygen atom by a Se atom as selenite in a miconazole derivative ( 25 ) leads to a decrease in the MIC value on the strain CPCC400616 of C. albicans .…”

Section: Discussionmentioning

confidence: 99%

“…80,90−94 An additional consideration of much importance is the enhanced antifungal efficacy of a wide range of molecules ascribed to the introduction of Se moieties into their structures as reported by several studies carried out in the past few years. 35,85,95,96 Also, the structures of the CYP51 inhibitors can be divided into four different parts, as illustrated in Figure 1, to design their novel analogues.…”

Section: Selenized Small Molecule Drugsmentioning

confidence: 99%

“…(ATCC SC5314). 96 These encouraging outcomes suggest that 1,2,3-selenadiazole derivatives can be a promising and feasible approach to overcoming fungal resistance and obtaining broad-spectrum candidates for clinical development.…”

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%

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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“…We carried out the GC-MS analysis using the previously described methodology. , Candida albicans (SC5314) was selected as the model strain in this experiment.…”

Section: Methodsmentioning

confidence: 99%

Developing Novel Coumarin-Containing Azoles Antifungal Agents by the Scaffold Merging Strategy for Treating Azole-Resistant Candidiasis

Yan,

Huang,

Zhao

et al. 2023

J. Med. Chem.

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The extensive use of antifungal drugs has resulted in severe drug resistance, making clinical treatment of fungal infections more difficult. Biofilm inhibitors can overcome drug resistance by inhibiting fungal biofilm formation. In this study, some coumarins with antibiofilm activity were merged into CYP51 inhibitors to produce novel molecules possessing potent antiresistance activity. As expected, most compounds exhibited excellent in vitro antifungal activity against pathogenic fungi, especially fluconazole-resistant candidiasis. Then, their mechanism was confirmed by sterol composition analysis and morphological observation. Biofilm inhibition and down-regulation of resistancerelated genes were employed to confirm the compounds' antiresistance mechanisms. Significantly, compound A32 demonstrated fungicidal activity against fluconazole-resistant strain 904. Most importantly, compound A32 showed potent in vivo antifungal activity against pathogenic fungi and fluconazole-resistant strains. Preliminary pharmacokinetic and toxicity tests demonstrated that the compounds possessed favorable druggability. Taken together, compound A32 represents a promising lead to develop novel antifungal agents for treating azole-resistant candidiasis.

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“…Further exploration of the therapeutic potential of new 1,2,3-thiadiazole or 1,2,3-selenadiazole is an active area of research. Previous studies have demonstrated that some of the new 1,-2,3-thiadiazole or 1,2,3-selenadiazole derivatives exhibit antifungal [1,2] antiviral [3,4], and anticancer activities [5]. e concept of isosteric exchange has long been used as a tool for modifying the activity of biologically important molecules.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Antimicrobial Activity of New 1,2,3-Thiadiazole and 1,2,3-Selenadiazole Derivatives

Al-Smadi

Esmadi

Al-Smadi

et al. 2022

Journal of Chemistry

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1,2,3-Thiadiazole, 1,2,3-selenadiazole, and semicarbazones that are prepared from ketones are promising moieties for lead compound development. New 1,2,3-thiadiazole (2c-4c) and 1,2,3-selenadiazole derivatives (2d–4d) were prepared from the corresponding semicarbazones (2b-4b). The semicarbazones (2b-4b) were prepared from the corresponding ketones (2a-4a). Characterization of the synthesized compounds was performed using infrared spectra (IR), proton nuclear magnetic resonance (1H-NMR) spectra, carbon nuclear magnetic resonance (13C-NMR), ultraviolet spectra, mass spectrometry, and elemental analysis. The antimicrobial activity of the prepared compounds was explored in vitro against various pathogenic microbes. All heterocyclic compounds had positive antimicrobial activity, but these activities varied in the extent of antimicrobial coverage. Compounds (2c) and (2d) had positive activity against Staphylococcus aureus and Escherichia coli but without any antipseudomonal activity. Compound (3c) had the most activity against Candida albicans with potential as a novel antifungal agent along with activity against some Gram-positive and Gram-negative bacteria. Compounds (4c) and (4d) exhibited broad-spectrum coverage in which both compounds demonstrated antimicrobial activity against all microorganisms explored. Interestingly, they both had substantial antipseudomonal activity against local resistant Pseudomonas aeruginosa and reference P. aeruginosa (ATCC 27853). This may suggest the potential for compounds (4c) and (4d) as novel broad-spectrum antibacterial agents with promising antipseudomonal activity. In conclusion, new 1,2,3-thiadiazole (2c-4c) and 1,2,3-selenadiazole (2d-4d) derivatives were identified as potential lead compounds for novel antibacterial agents.

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Discovery of 1,2,3-selenadiazole analogues as antifungal agents using a scaffold hopping approach

Cited by 13 publications

References 28 publications

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

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

Developing Novel Coumarin-Containing Azoles Antifungal Agents by the Scaffold Merging Strategy for Treating Azole-Resistant Candidiasis

Synthesis, Characterization, and Antimicrobial Activity of New 1,2,3-Thiadiazole and 1,2,3-Selenadiazole Derivatives

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