Antifungal screening and in silico mechanistic studies of an in-house azole library

Systemic Candida infections pose a serious public health problem with high morbidity and mortality. C. albicans is the major pathogen identified in candidiasis, however non-albicans Candida spp. with antifungal resistance are now more prevalent. Azoles are first-choice antifungal drugs for candidiasis, however they are ineffective for certain infections caused by the resistant strains. Azoles block ergosterol synthesis by inhibiting fungal CYP51, which leads to disruption of fungal membrane permeability. In this study, we screened for antifungal activity of an in-house azole library of 65 compounds to identify hit matter followed by a molecular modelling study for their CYP51 inhibition mechanism. Antifungal susceptibility tests against standard Candida spp. including C. albicans revealed derivatives 12 and 13 as highly active. Furthermore, they showed potent antibiofilm activity as well as neglectable cytotoxicity in a mouse fibroblast assay. According to molecular docking studies 12 and 13 have the necessary binding characteristics for effective inhibition of CYP51. Finally, molecular dynamics (MD) simulations of the C. albicans CYP51 (CACYP51) homology model's catalytic site complexed with 13 was stable demonstrating excellent binding. This article is protected by copyright. All rights reserved

Analyzing the effects of organizational trust and organizational commitment in anti-productivity behaviours in managerial approach dimension to achieve a strategic competitive advantage

It is observed that negative approaches in organizational functioning and attitudes towards work have recently become increasingly common. Such developments weaken employees’ feelings of commitment and dedication to the organization and work. To improve the organizational commitment and dedication of the employees, first, the causes of emotions that inhibit these emotions and solution methods to eliminate alienation to work should be analyzed. In this study, anti-productivity behaviours, their causes, factors that influence the formation of organizational trust and commitment, and the relations between anti-productivity behaviours will be evaluated