Anticancer efficacy of 3-(4-isopropyl) benzylidene-8-ethoxy, 6-methyl, chroman-4-one (SBL-060), a novel, dual, estrogen receptor-Akt kinase inhibitor in acute myeloid leukemia cells.

Estrogen receptor (ER) α is expressed in a subset of patient-derived acute myeloid leukemia (AML) cells, whereas Akt is predominantly expressed in most types of AML. Targeting AML with dual inhibitors is a novel approach to combat the disease. Herein, we examined a novel small molecule, 3-(4-isopropyl) benzylidene-8-ethoxy,6-methyl, chroman-4-one (SBL-060), capable of targeting AML cells by inhibiting ERα and Akt kinase. The chemical properties of SBL-060 were identified by proton nuclear magnetic resonance (1H-NMR), 13C-NMR, and mass spectroscopy. In silico docking was performed using an automated protocol with AutoDock-VINA. THP-1 and HL-60 cell lines were differentiated using phorbol 12-myristate 13-acetate. ERα inhibition was assessed using ELISA. The MTT assay assessed cell viability. Flow cytometry was performed for cell cycle, apoptosis, and p-Akt analyses. Chemical analysis identified the compound as 3-(4-isopropyl) benzylidene-8-ethoxy,6-methyl, chroman-4-one, which showed high binding efficacy toward ER, with a ΔGbinding score of -7.4 kcal/mol. SBL-060 inhibited ERα, exhibiting IC50 values of 448 and 374.3 nM in THP-1 and HL-60 cells, respectively. Regarding inhibited cell proliferation, GI50 values of SBL-060 were 244.1 and 189.9 nM for THP-1 and HL-60 cells, respectively. In addition, a dose-dependent increase in sub G0/G1 phase cell cycle arrest and total apoptosis was observed after treatment with SBL-060 in both cell types. SBL-060 also dose-dependently increased the p-Akt-positive populations in both THP-1 and HL-60 cells. Our results indicate that SBL-060 has excellent efficacy against differentiated AML cell types by inhibiting ER and Akt kinase, warranting further preclinical evaluations.

Knowledge, awareness, and attitudes toward antibiotic use and antimicrobial resistance among Saudi population.

Background Inappropriate use of antibiotics is a public health problem of great concern. Objective To evaluate knowledge of antibiotics, race, gender and age as independent risk factors for self-medication. Setting Residents and population from different regions of Saudi Arabia. Methods We conducted a cross sectional survey study among residents. Data were collected between June 2014 to May, 2015 from 1310 participants and data were recorded anonymously. The questionnaire was randomly distributed by interview of participants and included sociodemographic characteristics, antibiotics knowledge, attitudes and behavior with respect to antibiotics usage. Main outcome measure Population aggregate scores on questions and data were analyzed using univariate logistic regression to evaluate the influence of variables on self-prescription of antibiotics. Results The response rate was 87.7 %. A cumulative 63.6 % of participants reported to have purchased antibiotics without a prescription from pharmacies; 71.1 % reported that they did not finish the antibiotic course as they felt better. The availability of antibiotics without prescription was found to be positively associated with self-medication (OR 0.238, 95 % CI 0.17-0.33). Of those who used prescribed or non-prescribed antibiotics, 44.7 % reported that they kept left-over antibiotics from the incomplete course of treatment for future need. Interestingly, 62 % of respondents who used drugs without prescription agreed with the statement that antibiotics should be access-controlled prescribed by a physician. We also found significant association between storage, knowledge/attitudes and education. Conclusions The overall level of awareness on antibiotics use among residents in Saudi Arabia is low. This mandates public health awareness intervention programs to be implemented on the use of antibiotics.