Novel quinoline-based derivatives as the PqsR inhibitor against Pseudomonas aeruginosa PAO1.

Aims: The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps.

Design and synthesis of quinolinium-based derivatives targeting FtsZ for antibacterial evaluation and mechanistic study.

The discovery of small molecular inhibitors targeting essential and conserved bacterial drug targets such as FtsZ protein is a promising approach to fight against multi-drug resistant bacteria. In the present study, two new series of FtsZ inhibitors based on a 1-methylquinolinium scaffold were synthesized. The inhibitors possess a variety of substituent groups including the cyclic or linear amine skeleton at the 2- and 4-position of the quinolinium ring for structure-activity relationship study.

Rational design of small-molecules to recognize G-quadruplexes of c-MYC promoter and telomere and the evaluation of their in vivo antitumor activity against breast cancer.

DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket.

The study of 9,10-dihydroacridine derivatives as a new and effective molecular scaffold for antibacterial agent development.

The emergence of worldwide spreading drug-resistant bacteria has been a serious threat to public health during the past decades. The development of new and effective antibacterial agents to address this critical issue is an urgent action. In the present study, we investigated the antibacterial activity of two 9,10-dihydroacridine derivatives and their mechanism.

Molecular Recognition and Imaging of Human Telomeric G-Quadruplex DNA in Live Cells: A Systematic Advancement of Thiazole Orange Scaffold To Enhance Binding Specificity and Inhibition of Gene Expression.

A series of fluorescent ligands, which were systematically constructed from thiazole orange scaffold, was investigated for their interactions with G-quadruplex structures and antitumor activity. Among the ligands, compound was identified to exhibit excellent specificity toward telomere G4-DNA over other nucleic acids. The affinity of -Htg24 was almost 5 times higher than that of double-stranded DNA and promoter G4-DNA.

A small-sized benzothiazole-indolium fluorescent probe: the study of interaction specificity targeting c-MYC promoter G-quadruplex structures and live cell imaging.

A small-sized c-MYC promoter G-quadruplex selective fluorescent BZT-Indolium binding ligand was demonstrated for the first time as a highly target-specific and photostable probe for in vitro staining and live cell imaging and it was found to be able to inhibit the amplification of the c-MYC G-rich sequence (G-quadruplex) and down-regulate oncogene c-MYC expression in human cancer cells (HeLa).

Antibacterial activity of indolyl-quinolinium derivatives and study their mode of action.

Filamenting temperature-sensitive mutant Z (FtsZ) is recognized as a promising target for new antibiotics development because of its high conservatism and pivotal role in the bacteria cell division. The aromatic heterocyclic scaffold of indole is known showing merit medical functions in antiviral and antimicrobial. In the present study, a series of 1-methylquinolinium derivatives, which were integrated with an indole fragment at its 2-position and a variety of amino groups (cyclic or linear, mono- or di-amine) at the 4-position were synthesized and their antibacterial activities were evaluated.