ABSTRACT
A series of new 1,2,3-triazole-tethered coumarin conjugates linked by N-phenylacetamide was efficiently synthesized via the click chemistry approach in excellent yields. The synthesized conjugates were evaluated for their in vitro antifungal and antioxidant activities. Antifungal activity determination was carried out against fungal strains such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger and Cryptococcus neoformans. Compounds 7b, 7d, 7e, 8b and 8e displayed higher potency than the standard drug miconazole, with lower minimum inhibitory concentration values. Also, compound 7a exhibited potential radical scavenging activity as compared with the standard antioxidant butylated hydroxytoluene. In addition, a molecular docking study of the newly synthesized compounds was carried out, and the results showed a good binding mode at the active site of the fungal (C. albicans) P450 cytochrome lanosterol 14α-demethylase enzyme. Furthermore, the synthesized compounds were also tested for ADME properties, and they demonstrated potential as good candidates for oral drugs.
Subject(s)
Antifungal Agents/pharmacology , Antioxidants/pharmacology , Coumarins/pharmacology , Fungi/drug effects , Molecular Docking Simulation , Triazoles/pharmacology , Administration, Oral , Antifungal Agents/administration & dosage , Antifungal Agents/chemical synthesis , Antioxidants/administration & dosage , Antioxidants/chemical synthesis , Biological Availability , Click Chemistry , Coumarins/administration & dosage , Coumarins/chemical synthesis , Drug Design , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship , Triazoles/administration & dosage , Triazoles/chemical synthesisABSTRACT
In search for new fungicidal and free radical scavenging agents, we synthesized a focused library of 2-chloroquinoline based monocarbonyl analogs of curcumin (MACs). The synthesized MACs were evaluated for inâ vitro antifungal and antioxidant activity. The antifungal activity was evaluated against five different fungal strains such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger, and Cryptococcus neoformans, respectively. Most of the synthesized MACs displayed promising antifungal activity compared to the standard drug Miconazole. Furthermore, molecular docking study on a crucial fungal enzyme sterol 14α-demethylase (CYP51) could provide insight into the plausible mechanism of antifungal activity. MACs were also screened for inâ vitro radical scavenging activity using butylated hydroxytoluene (BHT) as a standard. Almost all MACs exhibited better antioxidant activity compared to BHT.
Subject(s)
Antifungal Agents/chemical synthesis , Antioxidants/chemistry , Curcumin/analogs & derivatives , Fungal Proteins/metabolism , Molecular Docking Simulation , Quinolines/chemistry , Antifungal Agents/metabolism , Antifungal Agents/pharmacology , Aspergillus/drug effects , Binding Sites , Candida albicans/drug effects , Catalytic Domain , Cryptococcus neoformans/drug effects , Curcumin/metabolism , Curcumin/pharmacology , Fungal Proteins/chemistry , Microbial Sensitivity Tests , Sterol 14-Demethylase/chemistry , Sterol 14-Demethylase/metabolismABSTRACT
A facile, highly efficient, and greener method for the synthesis of new 1,4-disubstituted-1,2,3-triazoles was conducted using [Et3NH][OAc] as a medium by the implementation of ultrasound irradiation via click chemistry, affording excellent yields. The present synthetic method exhibited numerous advantages such as mild reaction conditions, excellent product yields, minimal chemical waste, operational simplicity, shorter reaction time, and a wide range of substrate scope. The synthesized compounds were further evaluated for in vitro antifungal activity against five fungal strains, and some of the compounds displayed equivalent or greater potency than the standard drug. A molecular docking study against the modelled three-dimensional structure of cytochrome P450 lanosterol 14α-demethylase was also performed to understand the binding affinity and binding interactions of the enzyme. Furthermore, the synthesized compounds were evaluated for DPPH radical scavenging activity and antitubercular activity against Mycobacterium tuberculosis H37Rv strain.
