Design, synthesis and biological evaluation of novel diazaspirodecanone derivatives containing piperidine-4-carboxamide as chitin synthase inhibitors and antifungal agents

Ji, Qinggang; Li, Bing; Chu, Yiwen; Wu, Hu; Du, Chuanbiao; Xu, Yajie; Shen, Yangli; Deng, Junfeng

doi:10.1016/j.bioorg.2021.105108

Cited by 8 publications

(5 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results indicate that virus infection of Aspergillus renders the fungus more susceptible to stresses affecting cell wall formation, especially towards NikZ, affecting chitin synthase. It would be of interest to compare the effects of other chitin synthase inhibitors, e.g., [ 29 ], to NikZ effects on infected vs. virus-free fungus in future studies. Stress induced by other inhibitors of cell wall synthesis (echinocandins) is not amplified by viral infection, indicating specificity for the kind of cell wall stress.…”

Section: Discussionmentioning

confidence: 99%

Polymycovirus Infection Sensitizes Aspergillus fumigatus for Antifungal Effects of Nikkomycin Z

Sass

Kotta‐Loizou

Martinez

et al. 2023

Viruses

View full text Add to dashboard Cite

Infection with Aspergillus fumigatus polymycovirus 1 (AfuPmV-1) weakens resistance of Aspergillus fumigatus common reference strain Af293 biofilms in intermicrobial competition with Pseudomonas aeruginosa. We compared the sensitivity of two infected and one virus-free Af293 strains to antifungal drugs. All three were comparably sensitive to drugs affecting fungal membranes (voriconazole, amphotericin) or cell wall glucan synthesis (micafungin, caspofungin). In contrast, forming biofilms of virus-free Af293 were much more resistant than AfuPmV-1-infected Af293 to nikkomycin Z (NikZ), a drug inhibiting chitin synthase. The IC50 for NikZ on biofilms was between 3.8 and 7.5 µg/mL for virus-free Af293 and 0.94–1.88 µg/mL for infected strains. The IC50 for the virus-free A. fumigatus strain 10AF was ~2 µg/mL in most experiments. NikZ also modestly affected the planktonic growth of infected Af293 more than the virus-free strain (MIC 50%, 2 and 4 µg/mL, respectively). Virus-free Af293 biofilm showed increased metabolism, and fungus growing as biofilm or planktonically showed increased growth compared to infected; these differences do not explain the resistance of the virus-free fungus to NikZ. In summary, AfuPmV-1 infection sensitized A. fumigatus to NikZ, but did not affect response to drugs commonly used against A. fumigatus infection. Virus infection had a greater effect on NikZ inhibition of biofilm than planktonic growth.

show abstract

Section: Discussionmentioning

confidence: 99%

Polymycovirus Infection Sensitizes Aspergillus fumigatus for Antifungal Effects of Nikkomycin Z

Sass

Kotta‐Loizou

Martinez

et al. 2023

Viruses

View full text Add to dashboard Cite

show abstract

“…Through systematic structural modifications, these researchers have been able to finetune the inhibitory potency and selectivity of these derivatives, enabling the development of lead compounds with enhanced bioactivity and reduced off-target effects. Besides, arylpiperidine and arylpiperazine derivatives exhibit diverse pharmacological activities beyond tyrosinase inhibition, making them attractive candidates for multifunctional therapeutic agents [48][49][50][51]. Very recently, while our study was in progress, an experimental and computational investigation involving compounds containing the 3-chloro-4-fluorophenyl group underscored the significance of this moiety in the inhibition of Agaricus bisporus TYR [52].…”

Section: Molecular Docking and MD Simulationsmentioning

confidence: 84%

Unlocking Tyrosinase Inhibition: Insights from Molecular Dynamics and Binding Free Energy Studies of Novel Arylpiperidine and Arylpiperazine-Based Inhibitors

Martins,

Bentes,

Lameira

et al. 2023

Preprint

View full text Add to dashboard Cite

Tyrosinases (TYR) play an important role in oxidizing phenols and catechols, leading to the formation of catechols and ortho-quinones, respectively. In mammals, TYR catalyzes the conversion of L-Tyrosine to quinone, a pivotal step in melanogenesis, which generates melanin pigments responsible for protecting against UV radiation and oxidative stress. Given TYR's importance in melanin-related disorders and cosmetic applications, the inhibition of TYR has garnered attention for controlling melanin production. However, current inhibitors like hydroquinone, arbutin, and kojic acid (KA) have limitations in terms of side effects and effectiveness. A novel class of TYR inhibitors featuring arylpiperidine and arylpiperazine components has demonstrated potent inhibitory activity. This study presents a computational analysis of these inhibitors using molecular docking, molecular dynamics (MD) simulations, and the Linear Interaction Energy (LIE) method was used to estimate binding free energies. The arylpiperidine and arylpiperazine inhibitors exhibit remarkable stability within the TYR active site during simulations. The van der Waals interactions are notably sustained, indicating effective inhibition mechanisms. The results from LIE calculations closely align with experimental binding affinities. In summary, these results contribute to the understanding of TYR inhibition and underscore the potential of arylpiperidine and arylpiperazine derivatives as effective agents for modulating melanin production in both cosmetic and pharmaceutical applications. Overall, this study sheds light on the intricate interactions between inhibitors and TYR, opening avenues for the development of novel therapies and interventions.

show abstract

“…Based on screening, compound 29 was reported as the most active antifungal agent against aspergillus flavus with MIC of 0.07 μg/ mL, better than reference fluconazole MIC of 0.209 μg/mL. [79] Yun et al synthesized piperidine-containing fluoroquinolone hybrids and evaluated them for antibacterial activity. Compound 30 was more potent than levofloxacin against MRSA, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumonia, and Shigella sonnei with MIC ranging from 0.125-4 μg/mL.…”

Section: Antibacterial and Antifungal Agentsmentioning

confidence: 99%

“…and screened for antifungal activity. Based on screening, compound 29 was reported as the most active antifungal agent against aspergillus flavus with MIC of 0.07 μg/mL, better than reference fluconazole MIC of 0.209 μg/mL [79] . Yun et al .…”

Section: Antibacterial and Antifungal Agentsmentioning

confidence: 99%

Versatile Therapeutic Values of N‐Containing Heterocycles Benzimidazole, Piperazine and Piperidine Hybrids

Zala,

Kumari

2023

ChemistrySelect

View full text Add to dashboard Cite

Nitrogen‐containing benzimidazole, piperazine, and piperidine are significant pharmacophores in medicinal chemistry and drug development. Many medications, lead compounds, and various reagents have these N‐containing scaffolds. This review concentrated on the development of novel therapeutic agents as well as the broad range of pharmacological actions demonstrated by benzimidazole, piperazine, and piperidine hybrids. The review emphasizes these hybrids′ potential, range, and medical significance. The review also discusses the structural criteria for benzimidazole, piperazine, and piperidine hybrids created by diverse chemists to be physiologically effective against a variety of disorders.

show abstract

Design, synthesis and biological evaluation of novel diazaspirodecanone derivatives containing piperidine-4-carboxamide as chitin synthase inhibitors and antifungal agents

Cited by 8 publications

References 35 publications

Polymycovirus Infection Sensitizes Aspergillus fumigatus for Antifungal Effects of Nikkomycin Z

Polymycovirus Infection Sensitizes Aspergillus fumigatus for Antifungal Effects of Nikkomycin Z

Unlocking Tyrosinase Inhibition: Insights from Molecular Dynamics and Binding Free Energy Studies of Novel Arylpiperidine and Arylpiperazine-Based Inhibitors

Versatile Therapeutic Values of N‐Containing Heterocycles Benzimidazole, Piperazine and Piperidine Hybrids

Contact Info

Product

Resources

About