Design, synthesis and antifungal activities of novel triazole derivatives with selenium-containing hydrophobic side chains

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

doi:10.1016/j.bmcl.2022.129044

Cited by 9 publications

(11 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…145 Furthermore, the selenoderivatives 1 and 2 of fluconazole displayed similar cytotoxic properties compared to the unmodified drug. 95 Conversely, the replacement of its central scaffold with a 1,2,3-selenadiazole ring furnished compounds with an improved antifungal activity. 96 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%

“…On the one hand, amidst the different Se analogues of MMI, a shrinkage of the activity was observed for 49 . 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 .…”

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%

See 2 more Smart Citations

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

Morán-Serradilla,

Plano,

Sanmartín

et al. 2024

J. Med. Chem.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Selenized Small Molecule Drugsmentioning

confidence: 99%

See 1 more Smart Citation

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

Morán-Serradilla,

Plano,

Sanmartín

et al. 2024

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…But unfortunately, resistance to drugs complicates the treatment process . Studies have shown that ergosterol biosynthesis is crucial for the survival of fungi, and many antifungal drug targets have been found based on these studies …”

Section: Introductionmentioning

confidence: 99%

“…4 Studies have shown that ergosterol biosynthesis is crucial for the survival of fungi, and many antifungal drug targets have been found based on these studies. 5 As antifungal agents, azoles act through inhibition of fungal lanosterol 14-α-demethylases (CYP51), an enzyme required to catalyze the oxidative removal of 14-α-demethylases in sterol biosynthesis by fungi. 6 Fluconazole is used in the treatment of fungal infections as a drug with high oral bioavailability and therapeutic index.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antifungal Activities, Molecular Docking and Molecular Dynamic Studies of Novel Quinoxaline-Triazole Compounds

Osmaniye,

Baltacı Bozkurt,

Levent

et al. 2023

ACS Omega

View full text Add to dashboard Cite

Uncontrolled use of antifungal drugs affects the development of resistance to existing drugs. Azole antifungals constitute a large part of antifungal therapy. Therefore, there is a need for new azole antifungals. Within the scope of this study, 17 new triazole derivative compounds were synthesized. Structure determinations were clarified by spectroscopic analysis methods ( 1 H-NMR, 13 C-NMR, HRMS). In addition, structure matching was completed using two-dimensional NMR techniques, HSQC, HMBC and NOESY. The antifungal effects of the compounds were evaluated on Candida strains by means of in vitro method. Compound 5d showed activity against Candida glabrata with a MIC 90 = 2 μg/mL. Compound 5d showed activity against Candida krusei with a MIC 90 = 2 μg/mL. This activity value, which is higher than fluconazole, is promising. In addition, the biofilm inhibition percentages of the compounds were calculated. Molecular docking and molecular dynamics simulations performed with compound 5d are in harmony with activity studies.

show abstract

New 5,6‐dihydrobenzo[h]quinoline derivatives as potential demethylase inhibitors (DMIs): design, synthesis, activity evaluation and molecular dynamics simulation

Xie,

Wang,

Bao

et al. 2024

Pest Management Science

View full text Add to dashboard Cite

BACKGROUNDBipolaris maydis is a serious plant fungus and strongly affects the yield and quality of crops. The main control strategy is the employment of fungicides. To research efficient fungicide with novel structure, a series of novel 5,6‐dihydrobenzo[h]quinoline derivatives were designed and synthesized.RESULTSThirty‐six novel 5,6‐dihydrobenzo[h]quinoline analogues were designed and synthesized. The assay results showed that most compounds exhibited significant fungicidal activity against Pyricularia oryzae, Bipolaris maydis, Sclerotinia sclerotiorum, Penicillium digitatum and Valsa mali at 16 μg mL−1. Compounds 4 h, 5e, 6a and 6b showed better antifungal activity than fluquinconazole against B. maydis. Their half maximal effective concentration (EC50) values were 0.732, 0.283, 0.529, 0.644 and 0.826 μg mL−1, respectively. Furthermore, the bioactive compounds were determined against sterol 14α‐demethylase (CYP51). The results indicated that they displayed prominent inhibiting activities, 4 h, 5e, 6a and 6b also had better inhibitory activities than fluquinconazole against CYP51. Their half maximal inhibitory concentration (IC50) values were 0.840, 0.315, 0.601, 0.750 and 1.018 μg mL−1, respectively. The fluorescent quenching tests of proteins indicated that the quenching patterns of compounds 5e and 6a were analogous to fluquinconazole. The molecular dynamics (MD) simulations indicated that compound 5e possessed stronger affinity than fluquinconazole to CYP51.CONCLUSIONThe results of the present study displayed that novel 5,6‐dihydrobenzo[h]quinoline derivatives could be one scaffold of potential CYP51 inhibitor and will provide some valuable information for the research and development of new fungicides. © 2024 Society of Chemical Industry.

show abstract

Design, synthesis and antifungal activities of novel triazole derivatives with selenium-containing hydrophobic side chains

Cited by 9 publications

References 13 publications

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

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

Synthesis, Antifungal Activities, Molecular Docking and Molecular Dynamic Studies of Novel Quinoxaline-Triazole Compounds

New 5,6‐dihydrobenzo[h]quinoline derivatives as potential demethylase inhibitors (DMIs): design, synthesis, activity evaluation and molecular dynamics simulation

Contact Info

Product

Resources

About