OBJECTIVE: The objective of the present study was to investigate the effects of alkoxy chain length and 1-hydroxy group on anticolorectal cancer activity of a series of 2-bromoalkoxyanthraquinones and corroborate it with their in silico properties.
METHODS: In vitro anticancer activity of 2-bromoalkoxyanthraquinones was evaluated against HCT116, HT29, and CCD841 CoN cell lines, respectively. Molecular docking was performed to understand the interactions of these compounds with putative p53 and KRAS targets (7B4N and 6P0Z).
RESULTS: 2-Bromoalkoxyanthraquinones with the 1-hydroxy group were proven to be more active than the corresponding counterparts in anticancer activity. Among the tested compounds, compound 6b with a C3 alkoxy chain exhibited the most promising antiproliferation activity against HCT116 cells (IC50 = 3.83 ± 0.05 μM) and showed high selectivity for HCT116 over CCD841 CoN cells (SI = 45.47). The molecular docking reveals additional hydrogen bonds between the 1-hydroxy group of 6b and the proteins. Compound 6b has adequate lipophilicity (cLogP = 3.27) and ligand efficiency metrics (LE = 0.34; LLE = 2.15) close to the proposed acceptable range for an initial hit.
CONCLUSION: This work highlights the potential of the 1-hydroxy group and short alkoxy chain on anticolorectal cancer activity of 2-bromoalkoxyanthraquinones. Further optimisation may be warranted for compound 6b as a therapeutic agent against colorectal cancer.
METHODS: A cross sectional study was performed in an IBD tertiary care center. Data was obtained from patients with IBD attending outpatient clinics from January 1st, 2021 until November 1st, 2021. Adult patients, older than 18 years, with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were recruited. The primary outcome was the association between BMI and medication used in IBD. The secondary outcome was the association between BMI and disease type and location in patients with IBD.
RESULTS: The study included a total of 528 patients of which, 66.5% have CD. Patients with normal weight comprises 55.9% of the participants, while those who are underweight, overweight or obese are 3.4, 28.2, and 12.5%, respectively. None of the underweight patients had UC. Among the normal weight, overweight and obese BMI categories, 34.6% vs. 36.2% vs. 31.8% had UC, respectively. Patients who are on tumor necrosis factor inhibitors (anti-TNF) with an immunomodulator (anti-TNF combination), are more likely to be overweight or obese than patients who are not on anti-TNF combination (OR 2.86, 95% CI 1.739-4.711, p < 0.001). Patients on vedolizumab are twice as likely to be overweight or obese than patients not on vedolizumab (OR 2.23, 95% CI 1.086-4.584, p < 0.05). Patients with ileocolonic CD are more likely to be overweight or obese compared to other subtypes of CD (OR 1.78, 95% CI 1.14-2.77, p = 0.01).
CONCLUSION: Many patients with IBD are either obese or overweight. Patients with IBD who are on anti-TNF combination therapy or vedolizumab monotherapy are more likely to be obese and overweight. In addition, patients will ileocolonic CD are more likely to be obese or overweight.