Infective diseases have become health threat of a global proportion due to appearance and spread of microorganisms resistant to majority of therapeutics currently used for their treatment. Therefore, there is a constant need for development of new antimicrobial agents, as well as novel therapeutic strategies. Quinolines and quinolones, isolated from plants, animals, and microorganisms, have demonstrated numerous biological activities such as antimicrobial, insecticidal, anti-inflammatory, antiplatelet, and antitumor. For more than two centuries quinoline/quinolone moiety has been used as a scaffold for drug development and even today it represents an inexhaustible inspiration for design and development of novel semi-synthetic or synthetic agents exhibiting broad spectrum of bioactivities. The structural diversity of synthetized compounds provides high and selective activity attained through different mechanisms of action, as well as low toxicity on human cells. This review describes quinoline and quinolone derivatives with antibacterial, antifungal, anti-virulent, antiviral, and anti-parasitic activities with the focus on the last 10 years literature.

/pdf/quinolines-and-quinolones-as-antibacterial-antifungal-anti-ht2iq5vzgw.pdf

Quinolines and quinolones as antibacterial, antifungal, anti-virulence, antiviral and anti-parasitic agents

The resistance of pathogenic microbes to currently available antimicrobial agents has been considered a global alarming concern. Hence, close attention should be paid to the development of novel potent antimicrobials. Herein, we report the synthesis, in vitro antimicrobial evaluation, of two novel sets of quinoline derivatives as potential DNA gyrase and DHFR inhibitors. The design of new compounds depended on modifying the structural aspects of previously reported fluoroquinolones. In both sets, the methyl group replaced the fluorine atom at C-6. In the first set, the diverse heterocyclic fragments of reported antimicrobial potentials, including pyrazole, isoxazole, and pyrimidine, were attached to C-3 of the quinoline scaffold. In the second set, the quinolone ring was replaced with the pyrazolo[3,4-b]quinoline scaffold to examine the effect of this action on the antimicrobial activity and the in silico virtual binding with DNA gyrase and DHFR. The preliminary antimicrobial activity of new compounds was assessed against a panel of pathogenic microbes including Gram-positive bacteria (Streptococcus pneumonia and Bacillus subtilis), Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli), and fungal strains (Aspergillus fumigatus, Syncephalastrum racemosum, and Geotriucum candidum). Six derivatives displayed relatively potent antimicrobial activity with a percent activity range of 80–113% relative to ampicillin, gentamicin, and amphotericin B as reference antimicrobial agents. Molecular docking studies were conducted to predict the binding affinities of new compounds toward the active sites of DNA gyrase and DHFR as proposed therapeutic targets.

The antimicrobial potential and pharmacokinetic profiles of novel quinoline-based scaffolds: synthesis and in silico mechanistic studies as dual DNA gyrase and DHFR inhibitors

Rhodium-Catalyzed Selective C−H Bond Functionalization of Quinolines

The recent data (2007–2018) on the synthesis of thieno[2,3-b]pyridines are summarized and systematized.

Recent advances in the chemistry of thieno[2,3-b]pyridines 1. Methods of synthesis of thieno[2,3-b]pyridines

A small library of novel quinoline-3-carbaldehyde hydrazones (Series 1), acylhydrazones (Series 2), and arylsulfonylhydrazones (Series 3) bearing either a 1,2,4-triazole or benzotriazole ring at position 2 was prepared, characterized by elemental analyses and IR, NMR, and MS spectra, and then subjected to in vitro cytotoxicity studies on three human tumor cell lines: DAN-G, LCLC-103H, and SISO. In general, compounds 4, 6, and 8 substituted with a 1,2,4-triazole ring proved to be inactive, whereas the benzotriazole-containing quinolines 5, 7, and 9 elicited pronounced cancer cell growth inhibitory effects with IC50 values in the range of 1.23–7.39 µM. The most potent 2-(1H-benzotriazol-1-yl)-3-[2-(pyridin-2-yl)hydrazonomethyl]quinoline (5e) showed a cytostatic effect on the cancer cell lines, whereas N′-[(2-(1H-benzotriazol-1-yl)quinolin-3-yl)methylene]-benzohydrazide (7a) and N′-[(2-1H-benzotriazol-1-yl)quinolin-3-yl)methylene]-naphthalene-2-sulfonohydrazide (9h) exhibited selective activity against the pancreas cancer DAN-G and cervical cancer SISO cell lines. Based on the determined IC50 values, the compound 5e seems to be leading compound for further development as anticancer agent.

Synthesis, Structure, Chemical Stability, and In Vitro Cytotoxic Properties of Novel Quinoline-3-Carbaldehyde Hydrazones Bearing a 1,2,4-Triazole or Benzotriazole Moiety.

This review highlights the recently cited research data in the literature on the chemistry of 2-chloroquinoline-3-carbaldehyde and related analogs and their applications over the period from 2013 to 2017. It covers: synthesis of quinoline ring systems and reactions adopted to construct fused or binary quinoline-cord heterocyclic systems. The biological evaluation and the synthetic applications of the target compounds were illustrated.

/pdf/recent-advances-in-the-chemistry-of-2-chloroquinoline-3-zc9wk2lseq.pdf

Ayaa A. Gooda

Papers

Recent advances in the chemistry of 2-chloroquinoline-3-carbaldehyde and related analogs

Efficient Synthesis, Antimicrobial, Antioxidant Assessments and Geometric Optimization Calculations of Azoles‐ Incorporating Quinoline Moiety