Synthesis, in vitro evaluation and molecular docking of new pyrazole derivatives bearing 1,5,10,10a-tetrahydrobenzo[ g ]
- PDF / 1,370,770 Bytes
- 15 Pages / 595.276 x 790.866 pts Page_size
- 70 Downloads / 183 Views
ORIGINAL PAPER
Synthesis, in vitro evaluation and molecular docking of new pyrazole derivatives bearing 1,5,10,10a‑tetrahydrobenzo[g] quinoline‑3‑carbonitrile moiety as potent antibacterial agents Nadia A. A. Elkanzi1,2 · Hajer Hrichi1,3 · Rania B. Bakr4,5 · O. Hendawy4,6 · May M. Alruwaili1 · Enas D. Alruwaili1 · Rahaf W. Almamtrfi1 · Hadeel Kh. Alsharary1 Received: 30 June 2020 / Accepted: 3 October 2020 © Iranian Chemical Society 2020
Abstract In the current study, a new series of pyrazole derivatives 4a–d, 5a–d and 6a–d possessing 1,5,10,10a-tetrahydrobenzo[g] quinoline-3-carbonitrile moiety were synthesized by treating chalcones (3a–d) with hydrazine monohydrate/acetic anhydride, hydrazine monohydrate/formic acid and 4-chlorophenylhydrazine in ethanol, respectively. These reactions proceeded smoothly with satisfactory yields, and the obtained compounds were characterized using FTIR, 1H-NMR, 13C-NMR and elemental analyses. All the synthesized compounds were subjected to antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa bacteria and molecular docking studies. The antibacterial studies showed that all compounds exhibited good to excellent antibacterial activity against the tested bacterial strains. The structure–activity relationship studies revealed that the compounds 3b, 4b, 5b and 6b bearing a chlorine atom at the para position of the phenyl group attached to pyrazole moiety in displayed the highest antibacterial activity against all the tested bacteria exceeding the standard drug ampicillin. Moreover, the molecular docking results showed that the highest scores docking have been obtained from the most active antibacterial compounds 3b, 3d, 4b, 4d, 4c, 5b and 6b with good energy binding score within the active site of topoisomerase II DNA gyrase enzymes (PDB ID: 2XCS), suggesting that they can act by the inhibition of DNA replication. These compounds are auspicious candidates as antibacterial agents that would deserve further investigations. Keywords Heterocycles · Pyrazole · Quinoline · Antibacterial activity · Molecular docking
Introduction * Nadia A. A. Elkanzi [email protected] 1
Chemistry Department, College of Science, Jouf University, P.O. Box 2014, Sakaka, Saudi Arabia
2
Chemistry Department, Faculty of Science, Aswan University, P.O. Box 81528, Aswan, Egypt
3
National Institute of Applied Sciences and Technology, Carthage University, Centre Urbain Nord, B.P.N 676, 1080 Tunis Cedex, Tunisia
4
Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf 2014, Saudi Arabia
5
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni Suef 62514, Egypt
6
Department of Clinical Pharmacology, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt
The transmission and infection by microbes, such as bacteria and fungi, are considered the main origin of diseases in humans in both developed and developing countries [1, 2]. The major reason for the increas
Data Loading...
