In this study, new 7-chloro-4-aminoquinoline-benzimidazole compounds were synthesized and characterized by NMR, MS, and elemental analysis. These novel hybrids differ in the type of linker and in the substituent on the benzimidazole moiety. Their antiproliferative activities were evaluated on one non-tumor (MDCK1) and seven selected tumor (CaCo-2, MCF-7, CCRF-CEM, Hut78, THP-1, and Raji) cell lines by MTT test and flow cytometry analysis. The compounds with different types of linkers and an unsubstituted benzimidazole ring, 5d, 8d, and 12d, showed strong cytotoxic activity (the GI50 ranged from 0.4 to 8 µM) and effectively suppressed the cell cycle progression in the leukemia and lymphoma cells. After 24 h of treatment, compounds 5d and 12d induced the disruption of the mitochondrial membrane potential as well as apoptosis in HuT78 cells. The drug-like properties and bioavailability of the compounds were calculated using the Swiss ADME web tool, and a molecular docking study was performed on tyrosine-protein kinase c-Src (PDB: 3G6H). Compound 12d showed good solubility and permeability and bound to c-Src with an energy of −119.99 kcal/mol, forming hydrogen bonds with Glu310 and Asp404 in the active site and other residues with van der Waals interactions. The results suggest that compound 12d could be a leading compound in the further design of effective antitumor drugs.

Table of Contents POSTERS -RESEARCH 105 Genome structure and regulation 120 RNA function 129 Molecular evolution and phylogenetics 136 Epigenetics 147 Protein biosynthesis and expansion of genetic code 158 Autophagy and protein recycling 161 Proteolytic processing 169 Protein folding and misfolding 178 Protein localization and dynamics 197 Neurobiochemistry 212 Receptor-ligand interactions 222 Membranes 231 New approaches in structure determination 236 Molecular machines 240 Imaging for life: from molecules to organisms 244 Structures of nucleic acids 251 Metabolic engineering 255 Bionanotechnology 279 Designed regulatory circuits and genome editing 286 Plant biotechnology 295 Immunotherapy 299 New frontiers in medicinal chemistry 321 Pharmacogenomics and biomarkers 334 Stem cells and regenerative medicine 347 Bioinformatics and computational biology 360 Biochemistry of toxins 371 Mechanisms of microbiome-host interactions 376 Cellular organization 383 Molecular interactions of plants with the environment 395 Life on the edge -extremophilic/extremotolerant organisms 400 Cancer immunology and immunotherapy 412 Cancer initiation and progression 439 Immune and inflammatory disorders 461 Aging stress and neurodegeneration 477 Redox biology -oxidative stress signalling 494 The circadian clock and disease 496 Structural and functional glycobiology 499 Biomembranes and lipid mediators 501 Lipidomics POSTERS -EDUCATION 506 Educational technology and e-learning 507 Innovations and good practices Abstracts submitted to the virtual 45th FEBS Congress from 3rd to 8th July 2021 (originally planned to be held in Ljubljana, Slovenia) and accepted by the Congress Organizing Committee are published in this Supplement of FEBS Open Bio. Late-breaking abstracts are not included in this issue.

Psoriasis vulgaris (PV) is an autoinflammatory dermatosis of unknown etiology. Current evidence suggests a pathogenic role of γδT cells, but the growing complexity of this population has made the offending subset difficult to pinpoint. The work on γδTCRint and γδTCRhi subsets, which express intermediate and high levels of γδTCR at their surface, respectively, is particularly scarce, leaving their inner workings in PV essentially unresolved. We have shown here that the γδTCRint/γδTCRhi cell composition and their transcriptom are related to the differential miRNA expression by performing a targeted miRNA and mRNA quantification (RT-qPCR) in multiplexed, flow-sorted γδ blood T cells from healthy controls (n = 14) and patients with PV (n = 13). A significant loss of miR-20a in bulk γδT cells (~fourfold decrease, PV vs. controls) largely mirrored increasing Vδ1-Vδ2- and γδintVδ1-Vδ2- cell densities in the bloodstream, culminating in a relative excess of γδintVδ1-Vδ2- cells for PV. Transcripts encoding DNA-binding factors (ZBTB16), cytokine receptors (IL18R1), and cell adhesion molecules (SELPLG) were depleted in the process, closely tracking miR-20a availability in bulk γδ T-cell RNA. Compared to controls, PV was also associated with enhanced miR-92b expression (~13-fold) in bulk γδT cells that lacked association with the γδT cell composition. The miR-29a and let-7c expressions remained unaltered in case–control comparisons. Overall, our data expand the current landscape of the peripheral γδT cell composition, underlining changes in its mRNA/miRNA transcriptional circuits that may inform PV pathogenesis.

No abstract

No abstract