Design, synthesis and evaluation of 2-phenylpyrimidine derivatives as novel antifungal agents targeting CYP51 DOI

Zixuan Gao,

Jiachen Zhang,

Kejian Li

и другие.

RSC Medicinal Chemistry, Год журнала: 2023, Номер 15(2), С. 492 - 505

Опубликована: Ноя. 21, 2023

Invasive fungal infections, with high morbidity and mortality, have become one of the most serious threats to human health. There are a few kinds clinical antifungal drugs but large amounts them used, so there is an urgent need for new structural type drug. In this study, we carried out three rounds optimisation modification compound YW-01, which was obtained from preliminary screening group, by using strategy scaffold hopping. A series novel phenylpyrimidine CYP51 inhibitors were designed synthesised.

Язык: Английский

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

Cengiz Zobi,

Öztekin Algül

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

Процитировано

4

Conjugates of amphotericin B to resolve challenges associated with its delivery DOI
Vineet Jain, Keerti Jain, Harvinder Popli

и другие.

Expert Opinion on Drug Delivery, Год журнала: 2024, Номер 21(2), С. 187 - 210

Опубликована: Янв. 20, 2024

Introduction Amphotericin B (AmB), a promising antifungal and antileishmanial drug, acts on the membrane of microorganisms. The clinical use AmB is limited due to issues associated with its delivery including poor solubility bioavailability, instability in acidic media, intestinal permeability, dose aggregation state dependent toxicity, parenteral administration, requirement cold chain for transport storage, etc.

Язык: Английский

Процитировано

6

Antifungal Activity and Mechanism of Diaporthein B against Botryosphaeria dothidea in Prevention of Apple Ring Rot DOI

Hui-Fang Du,

Yahui Zhang,

Wan Li

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(38), С. 20892 - 20904

Опубликована: Сен. 10, 2024

Apple ring rot, caused by the pathogenic fungus

Язык: Английский

Процитировано

4

Polyene-Based Derivatives with Antifungal Activities DOI Creative Commons
Kwanele Ngece,

Thabisa L. Ntondini,

Vuyolwethu Khwaza

и другие.

Pharmaceutics, Год журнала: 2024, Номер 16(8), С. 1065 - 1065

Опубликована: Авг. 14, 2024

Polyenes are a class of organic compounds well known for their potent antifungal properties. They effective due to ability target and disrupt fungal cell membranes by binding ergosterol forming pores. Despite effectiveness as drugs, polyenes have several limitations, such high toxicity the host poor solubility in water. This has prompted ongoing research develop safer more efficient derivatives overcome limitations while enhancing activity. In this review article, we present thorough analysis polyene derivatives, structural modifications, influence on therapeutic effects against various strains. Key studies discussed, illustrating how modifications led improved By evaluating latest advancements synthesis highlight that incorporating amide linkers at carboxylic moiety molecules notably improves properties, evidenced 4, 5, 6G, 18. can help design development novel polyene-based with activities.

Язык: Английский

Процитировано

3

Effect of Defined Block Sequence Terpolymers on Antifungal Activity and Biocompatibility DOI Open Access

Hatu Gmedhin,

Sebastian Schaefer,

Nathaniel Corrigan

и другие.

Macromolecular Bioscience, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Invasive fungal infections cause over 3.7 million deaths worldwide annually, underscoring the critical need for new antifungal agents. Developing selective agents is challenging due to shared eukaryotic nature of both and mammalian cells. Toward addressing this, synthetic polymers designed mimic host defense peptides are promising candidates combating infections. This study investigates well-defined multiblock terpolymers with specific arrangements cationic, hydrophobic, hydrophilic groups, as potential The block sequence in these copolymers significantly impacts their minimum inhibition concentration (MIC) against Candida albicans biocompatibility. Furthermore, compared statistical counterparts, exhibit lower MIC values certain instances. Notably, triblock containing a central hydrophobic present an enhanced efficacy These findings highlight sequence-controlled versatile platform developing customized targeted therapies.

Язык: Английский

Процитировано

0

Alkyl Tail Variation on Chalcone‐Based Quaternary Pyridinium Salts as Rule‐of‐Thumb for Antimicrobial Activity DOI Creative Commons
Francesca Seghetti, Riccardo Ocello, Alessandra Bisi

и другие.

Archiv der Pharmazie, Год журнала: 2025, Номер 358(5)

Опубликована: Май 1, 2025

ABSTRACT Aiming at developing a new class of quaternary pyridinium salts, the lead compound 1 , characterized by pyridine‐3‐yl chalcone framework, was rationally modified inserting alkyl functions varying from 6 to 18 carbon units. Among set, some valuable compounds were identified. Derivatives 4 – primarily active against Staphylococcus aureus and Candida albicans respectively (MIC = 1.56 3.125 μM). In comparison, analogs 5 showed significant activities Escherichia coli 6.25 Interestingly, antimicrobial property as well their antibiofilm activity, occurred lower concentrations than cyto‐ erythrocyte toxicities, thus ensuring favorable safety profile. Structure–activity relationship analysis highlighted critical role tail length in optimal results observed for moieties ranging 10 14 Molecular dynamics studies performed on 2 modeling them Gram‐positive Gram‐negative membranes that derivatives, upon diffusing across periodic boundary conditions, able intercalate into microbial membranes. The difference diffusion rates provides useful information support diverse potencies newly designed salt.

Язык: Английский

Процитировано

0

Recent Advances in the Development of Antifungal Agents: Beyond Azoles, Polyenes, and Echinocandins DOI
Varsha Saini,

Sayed M. Safwan,

Devashish Mehta

и другие.

ACS Infectious Diseases, Год журнала: 2025, Номер unknown

Опубликована: Май 13, 2025

The escalating incidence of antimicrobial resistance to antifungal agents, alongside the emergence drug-resistant fungal strains, constitutes a significant threat potential global pandemic. In response, researchers are intensifying efforts identify novel compounds through diverse methodologies. Emerging strategies focus on innovative therapeutic targets that may reduce risk development while offering broad-spectrum efficacy against infections. Additionally, these approaches present cost-effectiveness and accelerated timelines. This review systematically categorizes range compounds, including peptides, cationic amphiphiles, small molecules, polymers, repurposed drugs, based their in inhibiting growth associated virulence factors. These exhibit notable activity across silico, vitro, vivo systems various pathogenic with several showing substantial promise for clinical application. Furthermore, highlights limitations standard antifungals elucidates mechanisms by which strains develop resistance. work aims engage distinctive field biology foster exploration new strategies.

Язык: Английский

Процитировано

0

Synthesis of Lipophilic Quinazolinone Template as Pollutant's Scavenger in Aqueous System and Evaluation of Its Anti‐Yeast Activity DOI
Pijus Ghorai, Shubhankar Ghorai,

P. Dutta

и другие.

Small, Год журнала: 2025, Номер unknown

Опубликована: Июнь 2, 2025

Abstract Non‐polymeric small amphiphiles have attained a significant role in various applications due to their defined and consistent molecular assembly hydrophobic/lipophilic balance. Synthesized Amphiphiles 2‐(5‐(bis(dodecylthio)methyl)‐2‐hydroxyphenyl)quinazolin‐4(3H)‐one (Q‐C12) has been recognized as new amphiphiles. The structurally Q‐C12 fluorescent quinazolinone moiety attached with two sulfur centers long alkyl chains. structural uniqueness of for the presence sulfur‐based chain backbone makes it selective towards detection mercury (Hg 2 ⁺) ions, followed by scavenging from aqueous system. It also shows its ability detect bind diethyl chlorophosphate (DCP), toxic stimulant nerve agents, using fluorescence efficacy. Each observation well studied NMR, fluorescence, DLS analysis. Further, behaves very effectively an anti‐yeast agent. yeast cell imaging study captured against Pichia sp. strain KG2 Fluorescent Q‐C12. development low‐cost functional amphiphile, claims great promise environmental monitoring, advanced material, biomedical innovations, offers multifunctional approach addressing key challenges pollution control healthcare.

Язык: Английский

Процитировано

0

Exploring the molecular structure of lipids in the design of artificial lipidated antifungal proteins DOI Creative Commons
Hendra Saputra, Muhammad Safaat,

Kazuki Uchida

и другие.

RSC Pharmaceutics, Год журнала: 2024, Номер 1(2), С. 372 - 378

Опубликована: Янв. 1, 2024

The antifungal activity of a small chitin-binding domain from chitinase was enhanced by the artificial lipidation with specific alkyl chain length and structure in presence amphotericin B.

Язык: Английский

Процитировано

1

Insights into the antifungal activity and mechanisms of cinnamon components against Aspergillus flavus and Penicillium citrinum DOI

Wanning Liu,

Tao Wang, Erzheng Su

и другие.

Food Research International, Год журнала: 2024, Номер 197, С. 115291 - 115291

Опубликована: Ноя. 5, 2024

Язык: Английский

Процитировано

1