Synthesis of novel methyl 7-[(hetero)arylamino]thieno[2,3-b] pyrazine-6-carboxylates and antitumor activity evaluation: effects in human tumor cells growth, cell cycle analysis, apoptosis and toxicity in non-tumor cells

Several novel methyl 7-[(hetero)arylamino]thieno[2,3-b]pyrazine-6-carboxylates were synthesized by Pd-catalyzed C–N Buchwald–Hartwig cross-coupling of either methyl 7-aminothieno[3,2-b]pyrazine-6-carboxylate with (hetero)arylhalides or 7-bromothieno[2,3-b]pyrazine-6-carboxylate with (hetero)arylamines in good-to-excellent yields (50% quantitative yield), using different reaction conditions, namely ligands and solvents, due to the different electronic character of the substrates. The antitumoral potential of these compounds was evaluated in four human tumor cell lines: gastric adenocarcinoma (AGS), colorectal adenocarcinoma (CaCo-2), breast carcinoma (MCF7), and non-small-cell lung carcinoma (NCI-H460) using the SRB assay, and it was possible to establish some structure–activity relationships. Furthermore, they did not show relevant toxicity against a non-tumor cell line culture from the African green monkey kidney (Vero). The most promising compounds (GI50 ≤ 11 µM), showed some selectivity either against AGS or CaCo-2 cell lines without toxicity at their GI50 values. The effects of the methoxylated compounds 2b (2-OMeC6H4), 2f and 2g (3,4- or 3,5-diOMeC6H3, respectively) on the cell cycle profile and induction of apoptosis were further studied in the AGS cell line. Nevertheless, even for the most active (GI50 = 7.8 µM) and selective compound (2g) against this cell line, it was observed that a huge number of dead cells gave rise to an atypical distribution on the cell cycle profile and that these cells were not apoptotic, which points to a different mechanism of action for the AGS cell growth inhibition.This research was funded by Fundação para a Ciência e Tecnologia (FCT)—Portugal, which financially supports CQUM (UID/QUI/686/2019), and also financed by the European Regional Develop- ment Fund (ERDF), COMPETE2020 and Portugal2020, and the PTNMR network also supported by Portugal2020. J.M.R. PhD grant (SFRH/BD/115844/2016) was financed by FCT, ESF (European Social Fund—North Portugal Regional Operational Program) and HCOP (Human Capital Operational Program). The authors are grateful to FCT, Portugal, for financial support through national funds FCT/MCTES to the CIMO (UIDB/00690/2020). L.B. and R.C.C. thank the national funding by FCT, Portugal, through the institutional scientific employment program-contract for their contracts

Intake of Plant Based Foods and Colorectal Cancer. A Case-Control Study in Romania

Colorectal cancer (CRC) represents the third most common type of cancer worldwide with high incidence rates in our country as well. Both dietary habits and lifestyle factors have a strong contribution in preventing colorectal cancer. A healthy dietary pattern based on adequate intake of fruit, non-starchy vegetables, and whole grains is associated with positive outcomes regarding CRC development. The aim of the present study was to evaluate the dietary intake of plant-based food and food groups, along with lifestyle habits of CRC patients. A case-control study was conducted during April 2015 – October 2017. Patients (n=151) recently diagnosed with CRC and undergoing conventional treatment were recruited from Medisprof Oncology Hospital. Controls (n=151) were selected randomly from generally healthy adults. Dietary and lifestyle data were collected during a face to face interview and the applied lifestyle questionnaire included 74 items. The results showed that intake of specific food groups with high content of bioactive components was significantly higher in the control group compared to the CRC group (p<0.05), even though overall vegetable intake was similar between groups (p=0.51). Results also showed significant lower intakes of fiber-rich foods such as whole grains, nuts and legumes in the CRC group

Determinants of Early Initiation of Breastfeeding among Mothers of Children Aged Less Than 24 Months in Northwestern Romania

Early initiation of breastfeeding (EIBF), defined as putting newborns to the breast within 1 h of birth, may have important benefits for both infant and mother. The aim of this study was to assess EIBF practices and its determinants in northwestern Romania. This cross-sectional study was conducted from March to June 2019, based on a sample of 1399 mothers of children aged less than 24 months. The sample was recruited from the community, from 29 cities and 41 communes distributed across the six counties of the northwestern region of Romania. Mothers responded by face-to-face interviews to a structured questionnaire. Multivariate logistic regression was used to identify factors independently associated with EIBF. Only 24.3% of the mothers initiated breastfeeding within 1 h of birth. Delivering at a private hospital (adjusted odds ratio (AOR): 5.17, 95% confidence interval (CI) 3.87, 6.91), vaginal delivery (AOR: 4.39, 95% CI 3.29, 5.88), mother&ndash;newborn skin-to-skin contact for 1 h or more (AOR: 55.6, 95% CI 23.0, 134.2), and breastfeeding counseling during antenatal visits (AOR: 1.48, 95% CI 1.12, 1.97) were factors associated with increased likelihood of EIBF. Overall, the practice of EIBF was poor. Targeting modifiable factors associated with EIBF may be used to improve early initiation practice

Breastfeeding Practices and Determinant Factors of Exclusive Breastfeeding among Mothers of Children Aged 0–23 Months in Northwestern Romania

In terms of breastfeeding (BF) practices in Romania, there is a lack of up-to-date data. The aim of the present study was to assess current BF practices, and to investigate the factors associated with exclusive BF (EBF) under 6 months of age in northwestern Romania. A structured questionnaire was used to collect data among 1399 mothers of children aged 0–23 months, recruited between March and June 2019, from the community. BF practices were evaluated based on the World Health Organization indicators for assessing infant and young child feeding practices, whereas determinants of EBF were explored using logistic regression models. Almost all mothers (95.7%) breastfed their child at least once. The EBF rate was 46.7%, the continued BF rate at one year of age was 54.2%, and the continued BF rate at 2 years of age was 30.3%. The place of delivery and parental leave duration were strong determinants of EBF. The improving rates observed in this study for all the BF practices assessed suggest the continuation of efforts to develop effective national policies and programs for promoting, protecting, and supporting BF in Romania. Particular emphasis should be given to the creation in maternity hospitals of an environment that is supportive towards breastfeeding