RESUMO
Evaluation of the drug ligand interactions between the C. cassia bio-compounds with the SAP-1 in C. albicans to explore the inhibitory medicinal potential of C. cassia bio-compounds by a computational approach is performed in the present investigation. Antimicrobial assay was done using agar well diffusion method with the crude aqueous and ethanolic extracts of the dried barks of C. cassia against C. albicans. 2D & 3D structures of the active bio-compounds of C. cassia were optimized and the 3D structure of SAP-1 was retrieved from the PDB data bank. In-silico inhibitory potential of the selected C. cassia biocompounds against SAP-1 was done by Auto Dock 2.0 and was visualized with Accelrys discovery studio visualizing tool with the assessment of the molecular properties of the ligands against SAP-1 by molinspiration calculations and further assessment for their drug likeliness. In-vitro analysis showed a promising anti-fungal activity of C. cassia extracts against C. albicans. Cinnamoyl E-acetate and Eugenyl acetate seem to possess promising inhibitory effect to target SAP-1 with a least binding energy of –5.33 and -5.21 Kcal/mol with four hydrogen bonds respectively. Molinspiration assessments showed zero violations for all the C. cassia compounds with the TPSA scores of <140 Å towards the best oral bioavailability. The findings of the study emphasize that cinnamaldehyde, cinnamoyal acetate and eugenol from C. cassia seem to possess a promising inhibitory effect against SAP-1 of C. albicans suggesting the medicinal value of the spice against SAP-1
RESUMO
Aims@#The aim of this study was to attempt to evaluate the antifungal activity of carvacrol in combination with fluconazole or amphotericin B against Candida albicans.@*Methodology and results@#Antifungal susceptibilities to carvacrol alone and in combination with fluconazole or amphotericin B were performed using the CLSI standard reference method against clinical isolates of C. albicans isolated from the immuno-compromised patients. Proteinase production assay and the expression of genes associated with secreted aspartyl proteinases synthesis (SAP1 and SAP2) were carried out to evaluate the antifungal activity of carvacrol in combination with fluconazole or amphotericin B against C. albicans. The carvacrol alone and in combination with fluconazole and amphotericin B exhibited strong inhibitory activity. The carvacrol, exhibited significant synergy and bpartial synergy with fluconazole or amphotericin B against the test isolates. The data indicated that combination of carvacrol with fluconazole or amphotericin B exerted antifungal effects through reducing SAP enzyme activity. The expression levels of SAP1 and SAP2 genes were down-regulated by carvacrol, fluconazole and amphotericin B alone. After carvacrol was employed in combination with fluconazole or amphotericin B, the expression levels of SAP1 and SAP2 genes demonstrated the lower expression in comparison to carvacrol alone.@*Conclusion, significance and impact of study@#These results provide proof of concept for the implementation of carvacrol alone or in combination with fluconazole or amphotericin B inhibitors of C. albicans.