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.
AIMS & OBJECTIVES: In this study, we synthesized thirteen derivatives of gallic acid and evaluated their antibacterial potential against seven multi-drug resistant bacteria, as well as cytotoxic effects against human embryonic kidney cell line in vitro. Methods: 13 compounds were successfully synthesized with moderate to good yield and evaluated. Synthesized derivatives were characterized by using nuclear magnetic resonance spectroscopy, mass spectrometry, and Fourier transformation infrared spectroscopy. Antibacterial activity was determined using microdilution while cytotoxicyt was assessed using MTT assay.
RESULTS: The results of antibacterial assay showed that seven out of thirteen compounds exhibited antibacterial effects with compound 6 and 13 being most potent against Staphylococcus aureus (MIC 56 μg/mL) and Salmonella enterica (MIC 475 μg/mL) respectively. On the other hand, most of these compounds showed lower cytotoxicity against human embryonic kidney cells (HEK 293), with IC50 values ranging from over 700 μg/mL.
CONCLUSION: Notably, compound 13 was found to be non-toxic at concentrations as high as 5000 μg/mL. These findings suggest that the present synthetic derivatives of gallic acid hold potential for further studies in the development of potent antibacterial agents.
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.
METHODS: This is a prospective, observational cohort study investigating short- and long-term AEs related to the BNT162b2 vaccine in patients with IBD (study group) after the first and second dose compared to healthy participants (control group). Patients were recruited at the time of attendance to the clinic or infusion rooms. Short term (<3 weeks) localized and systemic AEs were assessed via questionnaire. Follow-up phone-based survey was made to collect data on long term (up to 24 weeks) AEs.
RESULTS: A total of 408 patients answered the questionnaires, 204 patients in each group, the study and control group. No serious adverse events were reported in either the study or the control group after the first or the second dose. Participants in the control group reported more frequent pain at the injection site than those in the study group after the first dose [58 (57%) vs. 38 (37%) respectively, P = 0.005]. After the second dose, tiredness was reported more frequently in the control group [49 (48%)] compared to the study group [25 (24%) (P < 0.001)]. At 20-24 weeks post vaccination, 386 out of 408 (94.6%) patients were willing to participate in the follow-up phone based questionnaire [196 (96.1%) in the study group vs. 190 (93.1%) in the control group]. In both groups, none of the patients reported local, systemic, or severe adverse events (0 out of 386) at week 20-24 post second dose.
CONCLUSION: The BNT162b2 vaccine is safe in patients with IBD. No severe or long-term adverse events were reported in our study. The frequency of local and systemic adverse events after the second dose was generally higher among healthy participants compared to patients with IBD. Further studies including a larger cohort with a longer follow-up duration are needed to assess for possible rare adverse events.