Identification of potential CYP51 inhibiting anti-Aspergillus phytochemicals using molecular docking and ADME/T studies

Abstract

Aspergillosis caused by Aspergillus fumigatus is the second most common pulmonary disease after tuberculosis and recognized as threat to public health in last 2-3 decades. Immunosuppressive action and toxicity of currently available antifungals has necessitated search for new molecules with better efficacy, especially from medicinal plants. In this paper, we screened 1099 phytochemicals from 12 anti-Aspergillus medicinal plants by molecular docking against CYP51 and one best docked molecule from each plant having docking score better than voriconazole was further analysed for ADME/T properties. The best 03 molecules 2, 3 and 5 from Solanum xanthocarpum, Ocimum sanctum and Argemone Mexicana respectively showed better docking score, lowest blood-brain barrier permeability, high percentage of human oral absorption, good octanol-water partition coefficient and high rate of bioavailability in comparison with other molecules and voriconazole. These molecules may be considered as the best drug leads from this study. The study indicated that the selected molecules may be synthesized and further analyzed for in vitro/in vivo anti-Aspergillus activity to develop effective and safer antifungal drug.