Abstract
A series of 3-benzoyl imidazo[1,2-a]pyrimidines, obtained from N-heteroarylformamidines in good yields, was tested in silico and in vitro for binding and inhibition of seven Candida species (Candida albicans (ATCC 10231), Candida dubliniensis (CD36), Candida glabrata (CBS138), Candida guilliermondii (ATCC 6260), Candida kefyr, Candida krusei (ATCC 6358) and Candida tropicalis (MYA-3404)). To predict binding mode and energy, each compound was docked in the active site of the lanosterol 14α-demethylase enzyme (CYP51), essential for fungal growth of Candida species. Antimycotic activity was evaluated as the 50% minimum inhibitory concentration (MIC50) for the test compounds and two reference drugs, ketoconazole and fluconazole. All test compounds had a better binding energy (range: −6.11 to −9.43 kcal/mol) than that found for the reference drugs (range: 48.93 to −6.16 kcal/mol). In general, the test compounds showed greater inhibitory activity of yeast growth than the reference drugs. Compounds 4j and 4f were the most active, indicating an important role in biological activity for the benzene ring with electron-withdrawing substituents. These compounds show the best MIC50 against C. guilliermondii and C. glabrata, respectively. The current findings suggest that the 3-benzoyl imidazo[1,2-a]pyrimidine derivatives, herein synthesized by an accessible methodology, are potential antifungal drugs.
Highlights
Imidazo[1,2-a]pyrimidine is an important core with a wide range of biological activity, including antitumor [1,2,3], antihyperglycemic [4], antitubercular [5], antiviral [6,7], anti-HIV [8], and antiatherosclerosis [9]
The aim of the present study was to synthesize a series of 3-benzoyl imidazo[1,2-a]pyrimidine derivatives without conventional heating or microwave irradiation, and analyze these compounds by molecular docking studies to determine their binding mode and energy in relation to the active site of the CYP51 enzyme
By docking the test compounds in the active site of fungal CYP51, the binding mode and binding energy could be predicted in each case
Summary
Imidazo[1,2-a]pyrimidine is an important core with a wide range of biological activity, including antitumor [1,2,3], antihyperglycemic [4], antitubercular [5], antiviral [6,7], anti-HIV [8], and antiatherosclerosis [9]. There are reports on the application of imidazo[1,2-a]pyridine derivatives as antifungal agents [10,11,12]. Fungal infections have become a growing problem for patient health, implying great economic losses in hospitals [13,14]. Among the main fungal infections is invasive candidiasis, caused by species. A common treatment for these infections is the application of a broad-spectrum antifungal agent. Each of the CYP51 proteins has heme as its prosthetic group in the active site
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
