A recently developed dimerization/macrocyclization was employed to synthesize a series of macroheterocycles which were biologically evaluated, leading to the discovery of a number of potent cytotoxic agents (e.g., 27: GI50 = 51 nM against leukemia CCRF-CEM cell line; 29: GI50 = 99 nM against melanoma MDA-MB-435 cell line). Further biological studies support an apoptosis mechanism of action for these compounds involving deregulation of the tricarboxylic acid cycle activity and suppression of mitochondrial function in cancer cells.

Background: Disparities encountered by men and women physicians are well documented. However, evidence is lacking concerning the effects of gender on daily practice in the specialty of anesthesiology. Aims: To evaluate gender disparities perceived by female anesthesiologists. Setting and Design: Anonymous, voluntary 30-question, electronic secure REDcap survey. Materials and Methods: Survey link was sent via email, Twitter and the Facebook page, Physician Mom's Group. Instructions dictated that only female attending anesthesiologists participate and to partake in the survey one time. Statistical Analysis: Categorical variables were summarized using frequencies and percentages. Associations between categorical variables were tested using Chi-square test. Likert scale items were treated as continuous variables. T-tests were utilized to examine differences between those who reported burnout and those who did not. Results: 502 survey responses were received and analyzed. Female leadership was valued by 78%, yet only 47% had leadership roles. Being female was identified by 51% as negatively affecting career advancement and 90% perceived that women in medicine need to work harder than men to achieve the same career goals. Sexual harassment was experienced by 55%. Nearly 35% of institutions did not offer paid maternity leave. Burnout was identified in 43% of respondents and was significantly associated with work-life balance not being ideal ( P < 0.0001), gender negatively affecting career advancement ( P < 0.0001), experiencing sexual harassment at work ( P = 0.002), feeling the need to work harder than men ( P = 0.0033), being responsible for majority of household duties ( P = 0.0074), lack of weekly exercise ( P = 0.0135) and lack of lactation needs at work ( P = 0.0007). Conclusions: Understanding perceptions of female anesthesiologists may lead to actionable plans aimed at improving workplace equity or conditions.

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