Screening of Some Novel Isoxazoles Against C. Albicans for their Potential Use as antifungals: A Computational Approach

Antifungal resistance represents a major challenge for treating invasive fungal infections due to the limited arsenal of systemic antifungal agents. Azole resistance among Candida and Aspergillus species and the spread of such species is alarming. Isoxazoles play a significant role in the field of medicinal chemistry. The great interest associated with this class of compounds is their versatility as synthetic intermediates. Isoxazole derivatives were found to possess anti-bacterial, anti-fungal, anti-inflammatory, pesticidal and herbicidal activities. This study focuses on screening some novel isoxazoles against essential enzymes of C. albicans using molecular docking and dynamic studies. Molecular docking studies were performed on twenty novel isoxazoles against N- methyl transferase and DNA gyrase of C. albicans using GLIDE. 2D and 3D dock poses were visualized. Molecular dynamic study was carried out by DESMOND. Docking study in the XP mode has given significant results with good GScores and Emodel for NMT. Compound 2D (2-hydroxy derivative) was ranked highest among the derivatives. The ligands bound tightly with the target protein, indicated by of hydrogen bond interactions and pi-pi stacking interactions at the active site. Molecular dynamic studies were carried out for two complexes. Complex was found to be stable during molecular dynamic simulation. Docking study suggests that compound 2D (2-hydroxy derivative) may be prospective inhibitors of N-methyl transferase as it are specific in binding to the active site of this enzyme. Hence it may be considered as lead molecule for the design of potential inhibitors of C. albicans.