Design and Synthesis of 2-(4-Bromophenyl)Quinoline-4-Carbohydrazide Derivatives via Molecular Hybridization as Novel Microbial DNA-Gyrase Inhibitors

Abstract

Microbial DNA gyrase is regarded as an outstanding microbial target. Hence, 15 new quinoline derivatives (5–14) were designed and synthesized. The antimicrobial activity of the afforded compounds was pursued via in vitro approaches. The investigated compounds displayed eligible MIC values, particularly against G-positive Staphylococcus aureus species. Consequently, an S. aureus DNA gyrase supercoiling assay was performed, using ciprofloxacin as a reference control. Obviously, compounds 6b and 10 unveiled IC50 values of 33.64 and 8.45 μM, respectively. Alongside, ciprofloxacin exhibited an IC50 value of 3.80 μM. Furthermore, a significant docking binding score was encountered by compound 6b (−7.73 kcal/mol), surpassing ciprofloxacin (−7.29 kcal/mol). Additionally, both compounds 6b and 10 revealed high GIT absorption without passing the blood brain barrier. Finally, the conducted structure−activity relationship study assured the usefulness of the hydrazine moiety as a molecular hybrid for activity either in cyclic or opened form.

Novel Acrylate-Based Derivatives: Design, Synthesis, Antiproliferative Screening, and Docking Study as Potential Combretastatin Analogues

“…It is noteworthy that the polar interactions with Leu248, Met259, and Lys254 as well as the hydrophobic interactions involving the side chains of the aforementioned amino acid residues, as well as the hydrogen bond and hydrophobic interaction with Cys241, played a significant role in the intricate process of protein–ligand binding. These important interactions probably play a role in the exceptional tubulin inhibitory activity that CA-4, compounds 4b , and compound 5e all exhibit. − The results of the docking study point to compounds 4b and 5e′s extraordinary capacity to disrupt the process of tubulin polymerization as the likely cause of their potent cytotoxic effects on the MDA-MB-231 breast cancer cell line.…”

“…These important interactions probably play a role in the exceptional tubulin inhibitory activity that CA-4, compounds 4b , and compound 5e all exhibit. 39 − 41 The results of the docking study point to compounds 4b and 5e′s extraordinary capacity to disrupt the process of tubulin polymerization as the likely cause of their potent cytotoxic effects on the MDA-MB-231 breast cancer cell line.…”

Synthesis, biofilm formation inhibitory, and inflammation inhibitory activities of new coumarin derivatives

“…MBC has been performed by streaking of the two concentrations higher than MIC and the plates exhibiting no growth were considered as MBC 35 , 36 . Neomycine has been used as positive control 55 .…”

“…A volume of 200 μL of ethanol was added to each stained well to solubilize the dye 35 , 38 . Neomycine has been used as positive control 55 . Optical density (O.D.)…”

Exploring the antitumor potential of novel quinoline derivatives via tubulin polymerization inhibition in breast cancer; design, synthesis and molecular docking

“…The SwissADME web tool was used to estimate physicochemical and pharmacokinetics characteristics in silico (SwissADME: http:// www.swissadme.ch/). 59…”