The Significance of Mono‐ and Dual‐Effective Agents in the Development of New Antifungal Strategies

Chemical Biology & Drug Design, Год журнала: 2025, Номер 105(1)

Опубликована: Янв. 1, 2025

ABSTRACT Invasive fungal infections (IFIs) pose significant challenges in clinical settings, particularly due to their high morbidity and mortality rates. The rising incidence of these infections, coupled with increasing antifungal resistance, underscores the urgent need for novel therapeutic strategies. Current drugs target cell membrane, wall, or intracellular components, but resistance mechanisms such as altered drug‐target interactions, enhanced efflux, adaptive cellular responses have diminished efficacy. Recent research has highlighted potential dual inhibitors that simultaneously multiple pathways enzymes involved growth survival. Combining pharmacophores, lanosterol 14α‐demethylase (CYP51), heat shock protein 90 (HSP90), histone deacetylase (HDAC), squalene epoxidase (SE) inhibitors, led development compounds activity reduced resistance. This dual‐target approach, along chemical scaffolds, not only represents a promising strategy combating is also being utilized anticancer agents. review explores new agents employ mono‐, dual‐, multi‐target strategies combat IFIs. We discuss emerging targets, mechanisms, innovative approaches offer hope managing challenging infections.

Язык: Английский

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Novel flavonoid derivatives containing 1,2,4-triazolo[4,3-a]pyridine as potential antifungal agents: Design, synthesis, and biological evaluation

Journal of Saudi Chemical Society, Год журнала: 2023, Номер 28(2), С. 101797 - 101797

Опубликована: Дек. 23, 2023

A series of flavonoid derivatives containing 1,2,4-triazolo[4,3-a]pyridine were designed, synthesized and evaluated for their antifungal activity. Bioactivity tests showed that some target compounds exhibited the strong activity against Botrytis cinerea (B. cinerea), Sclerotinia sclerotiorum (S. sclerotiorum), Phomopsis sp. Among them, half maximal effective concentration (EC50) value S2 B. was 3.3 μg/mL, which less than control drug azoxystrobin (21.0 μg/mL). The EC50 S. 12.7 better (28.1 In addition, in vivo protective curative activities blueberry 92.0 79.8 % at 200 respectively, higher those (89.4 71.7%). Scanning electron microscopy (SEM) spore germination experiments could not only cause mycelium damage but also inhibited germination. Fluorescence (FM) observation, relative electrical conductivity measurement cytoplasmic leakage assays indicated affect cell membrane integrity by inducing lipid peroxidation increasing permeability as well causing contents. These results show had excellent inhibitory effects on cinerea, providing another supplement development new pesticides.

Язык: Английский

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Natural Substances as Valuable Alternative for Improving Conventional Antifungal Chemotherapy: Lights and Shadows

Journal of Fungi, Год журнала: 2024, Номер 10(5), С. 334 - 334

Опубликована: Май 5, 2024

Fungi are eukaryotic organisms with relatively few pathogenic members dangerous for humans, usually acting as opportunistic infections. In the last decades, several life-threatening fungal infections have risen mostly associated worldwide extension of chronic diseases and immunosuppression. The available antifungal therapies cannot combat this challenge because arsenal compounds is scarce displays low selective action, significant adverse effects, increasing resistance. A growing isolation outbreaks triggered by species formerly considered innocuous being recorded. From ancient times, natural substances harvested from plants been applied to folk medicine some them recently emerged promising antifungals. most used briefly revised herein. Combinations chemotherapeutic drugs products obtain more efficient gentle treatments also revised. Nevertheless, considerable research work still necessary before their clinical use can be generally accepted. Many a highly complex chemical composition, active principles partially unknown. Here, we survey field underlying lights shadows both groups. More studies involving strains necessary, but illustrate matter discussing potential applications combined carnosic acid plus propolis formulations.

Язык: Английский

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Rational modification of melatonin for broad‐spectrum antifungal agents discovery

Journal of Pineal Research, Год журнала: 2024, Номер 76(4)

Опубликована: Май 1, 2024

Abstract Natural products, known for their environmental safety, are regarded as a significant basis the modification and advancement of fungicides. Melatonin, low‐cost natural indole, exhibits diverse biological functions, including antifungal activity. However, its potential an agent has not been fully explored. In this study, series melatonin derivatives targeting mitogen‐activated protein kinase (Mps1) fungal pathogens were synthesized based on properties melatonin, among which trifluoromethyl‐substituted derivative Mt‐23 exhibited activity against seven plant pathogenic fungi, effectively reduced severity crop diseases, rice blast, Fusarium head blight wheat gray mold tomato. particular, EC 50 (5.4 µM) blast fungus Magnaporthe oryzae is only one‐fourth that isoprothiolane (22 µM), commercial fungicide. Comparative analyzes revealed simultaneously targets conserved Mps1 lipid Cap20. Surface plasmon resonance assays showed directly binds to we provide strategy developing agents by modifying resultant commercially valuable, eco‐friendly broad‐spectrum combat disease.

Язык: Английский

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Synthesis and Antifungal Activities of Novel Griseofulvin Derivatives as Potential Anti-Phytopathogenic Fungi Agents

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(23), С. 13015 - 13022

Опубликована: Май 29, 2024

The extensive and repeated application of chemical fungicides results in the rapid development fungicide resistance. Novel antifungal pesticides are urgently required. Natural products have been considered precious sources pesticides. It is necessary to discover by using natural products. Herein, 42 various griseofulvin derivatives were synthesized. Their activities evaluated vitro. Most them showed good activity, especially 3d exhibited a very broad spectrum most significant against 7 phytopathogenic fungi. In vivo activity suggested that protected apples tomatoes from serious infection These proved had potential be product-derived antiphytopathogenic fungi agent. Furthermore, docking analysis tubulin might one action sites 3d. reasonable believe worth further for discovery new

Язык: Английский

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A one-pot synthesized dual-emission MOFs-based ratiometric fluorescent sensor for hypersensitive and portable detection of griseofulvin

Sensors and Actuators B Chemical, Год журнала: 2025, Номер unknown, С. 137613 - 137613

Опубликована: Март 1, 2025

Язык: Английский

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Four unreported aporphine alkaloids with antifungal activities from Artabotrys hexapetalus

Fitoterapia, Год журнала: 2024, Номер 174, С. 105868 - 105868

Опубликована: Фев. 18, 2024

Язык: Английский

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Novel pyrazole-4-carboxamides and aromatic carboxamides derivatives containing a hydrazine moiety as potential SDHIs

Journal of Molecular Structure, Год журнала: 2023, Номер 1292, С. 136202 - 136202

Опубликована: Июль 13, 2023

Язык: Английский

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Cytotoxic glutarimide-containing polyketides isolated from Streptomyces sp. JCM 4793

The Journal of Antibiotics, Год журнала: 2024, Номер 77(9), С. 627 - 633

Опубликована: Май 30, 2024

Язык: Английский

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Novel Essential Oil-Based Thiosemicarbazone Compounds as Potential Fungicides in Controlling Postharvest Diseases of Citrus Fruit

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Сен. 20, 2024

To develop novel fungicides for controlling postharvest fungal diseases in citrus fruits, 12 essential oil (EO)-based thiosemicarbazones compounds, termed hydrazine-carbothioamide, were prepared according to the condensation method.

Язык: Английский

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