Design and Synthesis of Novel 1,3-Thiazole and 2-Hydrazinyl-1,3-Thiazole Derivatives as Anti- Candida Agents: In Vitro Antifungal Screening, Molecular Docking Study, and Spectroscopic Investigation of their Binding Interaction with Bovine Serum Albumin

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 19; p. 3435
• Main Authors: Pricopie, Andreea-Iulia, Ionuț, Ioana, Marc, Gabriel, Arseniu, Anca-Maria, Vlase, Laurian, Grozav, Adriana, Găină, Luiza Ioana, Vodnar, Dan C, Pîrnău, Adrian, Tiperciuc, Brîndușa, Oniga, Ovidiu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-09-2019; MDPI
• Subjects: 1,3-thiazole; anti-Candida; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Binding sites; Biological activity; Bovine serum albumin; Candida; Candida - drug effects; Drugs; Fluconazole; Fluorescence; fluorescence quenching; Fluorescence spectroscopy; Fungicides; Hydrogen bonds; Lanosterol; Ligands; Minimum inhibitory concentration; Molecular docking; Molecular Docking Simulation; NMR; Nuclear magnetic resonance; Pharmacokinetics; Serum albumin; Serum Albumin, Bovine - chemistry; Structure-Activity Relationship; anti-Candida; 1,3-thiazole; molecular docking; bovine serum albumin; fluorescence quenching
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24193435

In the context of there being a limited number of clinically approved drugs for the treatment of
sp.-based infections, along with the rapid development of resistance to the existing antifungals, two novel series of 4-phenyl-1,3-thiazole and 2-hydrazinyl-4-phenyl-1,3-thiazole derivatives were synthesized and tested in vitro for their anti-
potential. Two compounds (
and
) showed promising inhibitory activity against the pathogenic
strain, exhibiting substantially lower MIC values (7.81 μg/mL and 3.9 μg/mL, respectively) as compared with the reference drug fluconazole (15.62 μg/mL). Their anti-
activity is also supported by molecular docking studies, using the fungal lanosterol C14α-demethylase as the target enzyme. The interaction of the most biologically active synthesized compound
with bovine serum albumin was investigated through fluorescence spectroscopy, and the obtained data suggested that this molecule might efficiently bind carrier proteins in vivo in order to reach the target site.