ABSTRACT
The current study evaluated the cytotoxic activity of 11-(1,4-bisaminopropylpiperazinyl)5-methyl-5H-indolo[2,3-b]quinoline (BAPPN), a novel derivative of 5-methyl-5H-indolo[2,3-b]quinoline, against hepatocellular carcinoma (HepG2), colon carcinoma (HCT-116), breast (MCF-7), and lung (A549) cancer cell lines and the possible molecular mechanism through which it exerts its cytotoxic activity. BAPPN was synthesized and characterized with FT-IR and NMR spectroscopy. The binding affinity scores of BAPPN for caspase-3 PDB: 7JL7 was -7.836, with an RMSD of 1.483° A. In silico screening of ADME properties indicated that BAPPN showed promising oral bioavailability records in addition to their high gastrointestinal absorption and blood-brain barrier penetrability. BAPPN induced cytotoxicity, with IC50 values of 3.3, 23, 3.1, and 9.96 µg/mL against cancer cells HepG2, HCT-116, MCF-7, and A549, respectively. In addition, it induced cell injury and morphological changes in ultracellular structure, including cellular delayed activity, vanishing of membrane blebbing, microvilli, cytoplasmic condensation, and shrunken nucleus with more condensed chromatin autophagosomes. Furthermore, BAPPN significantly increased the protein expression of caspase-3 and tumor suppressor protein (P53). However, it significantly reduced the secretion of vascular endothelial growth factor (VEGF) protein into the medium and decreased the protein expression of proliferation cellular nuclear antigen (PCNA) and Ki67 in HepG2, HCT-116, MCF-7, and A549 cells. This study indicates that BAPPN has cytotoxic action against liver, colon, breast, and lung cancer cell lines via the up-regulation of apoptotic proteins, caspase-3 and P53, and the downregulation of proliferative proteins, VEGF, PCNA, and Ki67.
ABSTRACT
Introduction: COVID-19, is one of the biggest challenges facing humanity in the 21st century (1). The pandemic outbreak as affected all human activities, starting with healthcare and medical service passing with economy and social relationships, as well as political, religious and cultural enactments (2). The healthcare workers were the most affected fighting in the frontline working longer hours under a high risk of being infected (3). This study aims to assess the depression, anxiety and stress levels of the healthcare workforce (physicians, nurses, pharmacists and dentists) in the Middle East and North Africa-MENA-region. Methods: We invited healthcare workers in the Middle East to participate in our cross-sectional survey by answering to the DASS-21 questionnaire. Results: A total of 4,845 healthcare workers participated in the study. The participants were from 11 countries as follows: 436 from Egypt, 430 from Algeria, 458 from Iraq, 453 from Jordan, 473 from Libya, 428 from Palestine, 419 from Saudi Arabia, 452 from Sudan, 451 from Syria, 424 from Tunisia, and 421 from Yemen. The doctors among the healthcare workers were 51.7%, 19.0% were from the nursing staff, 16.8% were pharmacists, and 12.5% were from dentists. The depression level among the healthcare workers was as follows: 29.1% were normal, 13.7% were mildly depressed, 26.9% were moderately depressed, 14.4% were suffering from severe depression, and the depression state was extremely severe for the last 15.9%. At the same time, 29.1% were suffering from no anxiety, while 6.9% were at a mild level, 22.3% were at a moderate level, 13.4% were at a severe level, and 28.3% were at an extremely severe level. For the stress levels, 38.6% were normal, 14.9% were suffering from mild stress, 20.3% were moderate, 17.4% were severe, and the stress level was extremely severe for the other 8.9%. Discussion: This study indicates that in the Middle East and North Africa-MENA-region, the prevalence of depression, anxiety, and stress among the healthcare workforce during the COVID-19 pandemic was 70.9, 70.9, 61.4, respectively.