Design, Facile Synthesis and Characterization of Dichloro Substituted Chalcones and Dihydropyrazole Derivatives for Their Antifungal, Antitubercular and Antiproliferative Activities

Infectious diseases caused by fungi and mycobacteria pose an important problem for humankind. Similarly, cancer is one of the leading causes of death globally. Therefore, there is an urgent need for the development of novel agents to combat the deadly problems of cancer, tuberculosis, and also fungal infections. Hence, in the present study, we designed, synthesized, and characterized 30 compounds including 15 chalcones (2–16) and 15 dihydropyrazoles (17–31) containing dichlorophenyl moiety and also screened these compounds for their antifungal, antitubercular, and antiproliferative activities. Among these compounds, the dihydropyrazoles showed excellent antifungal and antitubercular activities whereas the chalcones exhibited promising antiproliferative activity. Among the dihydropyrazoles, compound 31 containing 2-thienyl moiety showed promising antifungal activity (MIC 5.35 µM), whereas compounds 22 and 24 containing 2,4-difluorophenyl and 4-trifluoromethyl scaffolds revealed significant antitubercular activity with the MICs of 3.96 and 3.67 µM, respectively. Compound 16 containing 2-thienyl moiety in the chalcone series showed the highest anti-proliferative activity with an IC₅₀ value of 17 ± 1 µM. The most active compounds identified through this study could be considered as starting points in the development of drugs with potential antifungal, antitubercular, and antiproliferative activities

LXR Deficiency Confers Increased Protection against Visceral Leishmania Infection in Mice

Leishmania spp. are protozoan single-cell parasites that are transmitted to humans by the bite of an infected sand fly, and can cause a wide spectrum of disease, ranging from self-healing skin lesions to potentially fatal systemic infections. Certain species of Leishmania that cause visceral (systemic) disease are a source of significant mortality worldwide. Here, we use a mouse model of visceral Leishmania infection to investigate the effect of a host gene called LXR. The LXRs have demonstrated important functions in both cholesterol regulation and inflammation. These processes, in turn, are closely related to lipid metabolism and the development of atherosclerosis. LXRs have also previously been shown to be involved in protection against other intracellular pathogens that infect macrophages, including certain bacteria. We demonstrate here that LXR is involved in susceptibility to Leishmania, as animals deficient in the LXR gene are much more resistant to infection with the parasite. We also demonstrate that macrophages lacking LXR kill parasites more readily, and make higher levels of nitric oxide (an antimicrobial mediator) and IL-1β (an inflammatory cytokine) in response to Leishmania infection. These results could have important implications in designing therapeutics against this deadly pathogen, as well as other intracellular microbial pathogens

Eyes wide open: perceived exploitation and its consequences

Drawing on the array of literature on exploitation from several social science disciplines, we propose a new way of seeing employer-employee relationships by introducing the concept of perceived exploitative employee-organization relationships, distinguish it from related concepts, and conduct five studies to develop a scale and test our theoretical model of the effects of such employee perceptions. Contributing to the Employee-Organization Relationships and workplace emotions literatures, perceived exploitation is defined as employees’ perceptions that they have been purposefully taken advantage of in their relationship with the organization, to the benefit of the organization itself. We propose and find that such perceptions are associated with both outward-focused emotions of anger and hostility toward the organization and inward-focused ones of shame and guilt at remaining in an exploitative job. In two studies including construction workers and a time-lagged study of medical residents, we find that the emotions of anger and hostility partially mediate the effects of perceived exploitation on employee engagement, revenge against the organization, organizational commitment, and turnover intentions, whereas the emotions of shame and guilt partially mediate the effects of perceived exploitation on employee burnout, silence, and psychological withdrawal

Directive versus empowering leadership: A field experiment comparing impacts on task proficiency and proactivity

Using a field experiment in the United Arab Emirates, we compared the impacts of directive and empowering leadership on customer-rated core task proficiency and proactive behaviors. Results of tests for main effects demonstrated that both directive and empowering leadership increased work unit core task proficiency, but only empowering leadership increased proactive behaviors. Examination of boundary conditions revealed that directive leadership enhanced proactive behaviors for work units that were highly satisfied with their leaders, whereas empowering leadership had stronger effects on both core task proficiency and proactive behaviors for work units that were less satisfied with their leaders. We discuss implications for both theory and practice. © Academy of Management Journal

Socioeconomic mobility and talent utilization of workers from poorer backgrounds: The overlooked importance of within-organization dynamics

Socioeconomic mobility, or the ability of individuals to improve their socioeconomic standing through merit-based contributions, is a fundamental ideal of modern societies. The key focus of societal efforts to ensure socioeconomic mobility has been on the provision of educational opportunities. We review evidence that even with the same education and job opportunities, being born into a poorer family undermines socioeconomic mobility due to processes occurring within organizations. The burden of poorer background might, ceteris paribus, be economically comparable to the gender gap. We argue that in the societal and scientific effort to promote socioeconomic mobility, the key context in which mobility is supposed to happen—organizations—as well as the key part of the life of people striving toward socioeconomic advancement—that as working adults—have been overlooked. We integrate the organizational literature pointing to key within-organizational processes impacting objective (socioeconomic) success with research, some emergent in organizational sciences and some disciplinary, on when, why, and how people from poorer backgrounds behave or are treated by others in the relevant situations. Integrating these literatures generates a novel and useful framework for identifying issues people born into poorer families face as employees, systematizes extant evidence and makes it more accessible to organizational scientists, and allows us to lay the agenda for future organizational scholarshi