Flexibility in the bridge of chalcone derivatives is important for the inhibition of cellular growth.

Chalcones and their derivatives are a privileged scaffold in medicinal chemistry, demonstrating numerous biological activities. These molecules have shown significant potential toward the development of novel cancer therapies. While much is known about modification to the chalcone aryl rings, little is known about conformations of the bridge between the aryl rings. Here we report the synthesis and biological evaluation of a series of molecules with flexible and rigid bridge conformations. Crystal structures of a select group of molecules were determined. Flexibility in the chalcone bridge containing the enone moiety was determined to be important for activity. Screening in three distinct cancer cell lines showed significant differences in the activity between the flexible and rigid conformations. Crystal structures suggest an increase in bond rotation and weakened π-bonding in the flexible chalcone bridge, which may contribute to the stronger anti-proliferative activity.

The latent tuberculosis infection cascade of care during the COVID-19 pandemic response in a Mid-Sized US city.

Background: The COVID-19 pandemic response may unintentionally disrupt multiple public health services, including tuberculosis control programs. We aimed to assess differences in the cascade of care for latent tuberculosis infection (LTBI) in a Midwest U.S. city during the COVID-19 pandemic response. Methods: We conducted a retrospective cohort study of adult patients who presented for LTBI evaluation at the Hamilton County Public Health Tuberculosis Clinic in Ohio between 2019 and 2020. The pre-COVID-19 response period was defined as 01/2019 to 02/2020, and the COVID-19 pandemic response period (first wave) was defined as 04/2020 to 12/2020. We reviewed electronic medical records to extract sociodemographic information, medical history, follow-up and treatment data to define steps within the LTBI cascade of care. Logistic regressions were used to assess factors associated with LTBI treatment acceptance and completion, adjusted by potential confounders and COVID-19 period. Results: Data from 312 patients were included. There was a significant decrease in the number of monthly LTBI referrals (median, 18 vs. 8, p = 0.02) and LTBI evaluations (median, 17.5 vs. 7, p < 0.01) during the first wave of COVID-19. The proportion for whom immigration was listed as the indication for LTBI testing also declined (30% vs. 9%; p < 0.01) during COVID-19. More LTBI diagnoses were based on interferon-gamma release assay (IGRA; 30% vs. 49%; p < 0.01) during the COVID-19 response period. The proportion of people in the clinic for whom treatment for LTBI was recommended was similar before and during COVID-19 (76% vs. 81%, p = 0.41), as was LTBI treatment acceptance rates (56% vs. 64%, p = 0.28), and completion rates (65% vs. 63%, p = 0.85). In multivariate analysis, LTBI treatment acceptance was associated with Hispanic ethnicity, younger age, male sex, IGRA being used for diagnosis, and non-healthcare occupation, independent of COVID-19 period. LTBI treatment completion was associated with taking a rifamycin-containing regimen, independent of COVID-19 period. Conclusion: We observed a significant decline in the number of monthly LTBI referrals and evaluations during the first wave of COVID-19, revealing an unintended negative impact of the COVID-19 response in our region. However, LTBI treatment acceptance and completion rates were not affected during COVID-19.