Quinoline-based promising anticancer and antibacterial agents, and some metabolic enzyme inhibitors

Okten S., AYDIN A., KOÇYİĞİT Ü. M. , Cakmak O. , ERKAN S., Andac C. A. , ...More

ARCHIV DER PHARMAZIE, vol.353, no.9, 2020 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 353 Issue: 9
  • Publication Date: 2020
  • Doi Number: 10.1002/ardp.202000086
  • Journal Indexes: Science Citation Index Expanded, Scopus, BIOSIS, CAB Abstracts, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: acetylcholinesterase enzyme inhibition, antibacterial, anticancer activity, carbonic anhydrase enzyme inhibition, DNA binding, molecular docking, quinolone, BIOLOGICAL EVALUATION, 8-SUBSTITUTED QUINOLINES, PHOSPHOLIPASE C-GAMMA-1, CRYSTAL-STRUCTURE, METAL-COMPLEXES, DERIVATIVES, EFFICIENT, DOCKING, SAR, CHOLINESTERASE


A series of substituted quinolines was screened for their antiproliferative, cytotoxic, antibacterial activities, DNA/protein binding affinity, and anticholinergic properties by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation, lactate dehydrogenase cytotoxicity, and microdilution assays, the Wolfe-Shimmer equality method, the Ellman method, and the esterase assay, respectively. The results of the cytotoxic and anticancer activities of the compounds displayed that 6-bromotetrahydroquinoline (2), 6,8-dibromotetrahydroquinoline (3), 8-bromo-6-cyanoquinoline (10), 5-bromo-6,8-dimethoxyquinoline (12), the novelN-nitrated 6,8-dimethoxyquinoline (13), and 5,7-dibromo-8-hydroxyquinoline (17) showed a significant antiproliferative potency against the A549, HeLa, HT29, Hep3B, and MCF7 cancer cell lines (IC50 = 2-50 mu g/ml) and low cytotoxicity (similar to 7-35%) as the controls, 5-fluorouracil and cisplatin. The compound-DNA linkages are hyperchromic or hypochromic, causing variations in their spectra. This situation shows that they can be bound to DNA with the groove-binding mode, withK(b)value in the range of 2.0 x 10(3)-2.2 x 10(5) M-1. Studies on human Gram(+) and Gram(-) pathogenic bacteria showed that the substituted quinolines exhibited selective antimicrobial activities with MIC values of 62.50-250 mu g/ml. All tested quinoline derivatives were found to be effective inhibitors of acetylcholinesterase (AChE) and the human carbonic anhydrase I and II isoforms (hCA I and II), withK(i)values of 46.04-956.82 nM for hCA I, 54.95-976.93 nM for hCA II, and 5.51-155.22 nM for AChE. As a result, the preliminary data showed that substituted quinolines displayed effective pharmacological features. Molecular docking studies were performed to investigate the binding modes and interaction energies for compounds2-17with AChE (PDB ID: 4EY6), hCA I (PDB ID: 1BMZ), and hCA II (PDB ID: 2ABE).