A series of cystargolide-based β-lactone analogues containing nitrogen atoms at the Pz portion of the scaffold were prepared and evaluated as proteasome inhibitors, and for their cytotoxicity profile toward several cancer cell lines. Inclusion of one, two or even three nitrogen atoms at the Pz portion of the cystargolide scaffold is well tolerated, producing analogues with low nanomolar proteasome inhibition activity, in many cases superior to carfilzomib. Additionally, analogue 8g , containing an ester and pyrazine group at Pz, was shown to possess significant activity toward RPMI 8226 cells (IC 50 = 21 nM) and to be less cytotoxic toward the normal tissue model MCF10A cells than carfilzomib.

Scheme1.Preparation of N3-and N9-substituteda nalogues of 1.Scheme2.Preparation of N3-and N9-substituteda nalogues of 2.

Leadership in a large urban school district in Florida is responsible for supporting school counselors and College Assistance Program (CAP) Advisors as they endeavor to conduct data-driven decision making. District leaders are also responsible for supporting school counselors and advisors in achieving accountability measures related to their performance. District leadership did not have a systematic framework to analyze factors related to performance, nor was it able to use the "language" of Human Performance Improvement to communicate and plan interventions to address performance issues faced by school counselors and advisors (Binder, 1998, p. 51). Leadership also needed recommendations that identify appropriate interventions that can be used to effectively support school counselors and advisors by reducing barriers and increasing enablers that influence use of data-driven decision-making.Binder's (1998, 2009, 2011) Six Boxes Model was used in this basic qualitative study to identify enablers and barriers involved with improved performance by high school counselors and advisors in data-driven decision-making. The top row of boxes pertains to environmental (data, resources, incentives) factors. The bottom row of boxes pertains to individual (knowledge, capacity, motives) factors. Data collection and analysis also followed this recommended order.Significant findings such as identified barriers in the lack of clear expectations and feedback regarding data-driven decision-making practices by counselors and advisors; an abundance of technology tools without time available during the school day for learning how to use them, along with clerical duties being assigned to counselors and advisors. Identified enablers included supportive leadership, counselors and advisors that are knowledgeable and willing to participate in data-driven decision-making practices, as well as being perceived as capable by district leaders. Counselors and advisors also expressed interest and willingness to participate in professional learning communities and/or communities of practice to improve their decision-making skills.Opportunities for further research may include measuring the effectiveness of the recommendations offered for reducing the barriers and enhancing the enablers identified through this study. Further exploration of how Binder's Model could be used to identify barriers and enablers for other Student Services professionals and their practices, such as those serving elementary and middle schools.