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

Abstract

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 novel N‐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 μg/ml) and low cytotoxicity (∼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, with Kb value in the range of 2.0 × 103–2.2 × 105 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 μg/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), with Ki 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 compounds 2–17 with AChE (PDB ID: 4EY6), hCA I (PDB ID: 1BMZ), and hCA II (PDB ID: 2ABE).

Quinoline‐based thiazolidinone derivatives as potent cytotoxic and apoptosis‐inducing agents through EGFR inhibition

“…Quinoline nucleus is a well‐known pharmacophore used for developing new biologically active compounds due to its synthetic versatility (Ökten et al, 2020) and medicinal applications (Kerru et al, 2020) as well as its incorporation in several natural and synthetic molecules (Perin et al, 2020; Shang, Morris‐Natschke, Liu, et al, 2018; Shang, Morris‐Natschke, Yang, et al, 2018). Over the years, many quinoline derivatives have been synthesized and reported for anticancer activity (Afzal et al, 2015; Gopaul et al, 2015; Mohamed & Abuo‐Rahma, 2020; Solomon & Lee, 2011).…”

Design, synthesis, molecular docking, and some metabolic enzyme inhibition properties of novel quinazolinone derivatives

“…Alzheimer's disease (AD), characterized by memory loss, language, and cognitive impairment, and severe behavioral abnormalities, is an agerelated and progressive neurodegenerative disorder. [22,23] At present, approximately 46 million people worldwide suffer from dementia, which is expected to reach 131.5 million by 2050. Due to the complex and unidentified etiology, many factors are perceived to be related to the occurrence and development of AD, including acetylcholine (ACh) decline, β-amyloid (Aβ) deposits, dyshomeostasis of biometals, oxidative stress, and hyperphosphorylated τ-protein.…”

Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines

“…Ökten and coworkers described the synthesis of 5,7-dibromo-8-hydroxyquinoline [ 47 ] in excellent yield via reaction of 8-hydroxyquinoline with two equivalents of bromine in chloroform. The target molecule exhibited IC 50 values (mg/mL) of 5.8, 17.6, 18.7, 5.4, 16.5, and >1000 against A549, FL, HeLa, HT29, MCF7, and Hep3B, respectively.…”