Fluorene/fluorenone carboxamide derivatives as selective light-up fluorophores for c-myc G-quadruplex.

The development of fluorescent dyes capable of selective recognition of G-quadruplexes is essential for studying its localization and biological functions. However, considering the G-quadruplex topologies may vary significantly, the synthesis of compounds showing both selectivity and strong fluorescence properties still remains a great challenge. Recently we have developed fluorene/fluorenone derivatives with structure-specific binding towards dsRNA, indicating its potential for structure-selective ligands. Herein, we report the synthesis of novel fluorene/fluorenone derivatives and their selectivity towards various DNA structures, particularly G-quadruplexes, two of which showed strong affinity to the proto-oncogene c-myc promoter G-quadruplex.

Synthesis, biological properties, and acid dissociation constant of novel naphthoquinone-triazole hybrids.

A series of novel 1,4-naphthoquinone-triazole hybrids, N-(3-amino-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-2-(4-R-1H-1,2,3-triazol-1-yl)acetamide, was synthesized by click chemistry in the presence of sodium ascorbate and copper(II) sulfate pentahydrate in 81-94% yield. Various biological properties of the synthesized compounds including DNA binding/cleavage, antioxidant, antibacterial and antifungal properties were evaluated. The DNA binding study was performed using dsDNA and G-quadruplex DNA. All of the compounds showed fluorescence increase in the presence of DNA, regardless of the structure. Up to 2.9 and 2.5 times fluorescence increase upon incubation with double stranded or G-quadruplex DNA was detected for 5f and 5g, respectively. The docking studies performed on dsDNA and G-quadruplex structures suggested compounds' mode of interactions were populated around the grooves. All of the compounds showed excellent DNA cleavage activity and 5e was almost degraded the plasmid DNA. The highest radical scavenging activity was obtained as 89.9% at 200 mg/L with 5d. However, the highest ferrous chelating activity was obtained as 68.1% at 200 mg/L with 5g. The compounds exhibited antimicrobial activity against Bacillus cereus, Legionella pneumophila subsp. pneumophila, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus hirae as bacteria strains and Candida albicans and Candida tropicalis as microfungus strains. The compounds exhibited antibacterial and antifungal activity in the range of 4-128 µg/mL and 16-128 µg/mL, respectively. The best antimicrobial activity was obtained with 5d and 5e with a MIC value of 4 µg/mL against Enterococcus hirae. The acid dissociation constants (pKa) were determined potentiometrically in 20% (v/v) dimethyl sulfoxide-water hydro-organic solvent at an ionic background of 0.1 mol/L of NaCl, at 25 ± 0.1 °C. Five pKa values were obtained for each ligand.

A novel method for conserved sequence extraction with prospective mutation prediction for SARS-CoV-2 PCR primer design.

While the whole genomic sequence of SARS-CoV-2 had been revealed, it was also demonstrated that the genome of SARS-CoV-2 exhibits identity with the genome of SARS-CoV and MERS-CoV with ratios of 80 % and 50 % respectively. In the light of SARS-CoV-2 infection and mortality data, diagnosis and treatment of COVID-19 came into prominence around the world. As such many RT-PCR kits have been developed by biotechnology scientists. However viruses are fast mutating organisms and in order to increase accuracy, feasibility in long term and avoid the off target results of RT-PCR assays, regions of viral genome with low mutation rate and designing of primers targeting these regions are quite important. In this scope, we are presenting a novel algorithm that could be used for finding low mutation rate regions of SARS-CoV-2 and primers that were designed according to findings from our algorithm in this study.