Abstract:
:Antibiotic-resistant bacteria continue to play an important role in human health and disease. Inventive strategies are necessary to develop new therapeutic leads to challenge drug-resistance problems. From this perception, new quinoline hybrids bearing bioactive pharmacophores were synthesized. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against nine bacterial pathogenic strains. The results revealed that most compounds exhibited good antibacterial activities. Seven compounds (2b, 3b, 4, 6, 8b, and 9c,d) displayed enhanced activity against methicillin-resistant Staphylococcus aureus compared to ampicillin. These compounds were subjected to an in vitro S. aureus DNA gyrase ATPase inhibition study, which revealed that compounds 8b, 9c, and 9d showed the highest inhibitory activity with IC50 values of 1.89, 2.73, and 2.14 μM, respectively, comparable to novobiocin (IC50 , 1.636 μM). Compounds 2a-c, 3a, 7c, 9c,d, and 10a,b revealed half the potency of levofloxacin in inhibiting the growth of Pseudomonas aeruginosa. As an attempt to rationalize the observed antibacterial activity for the most active compounds 8b, 9c, and 9d, molecular docking in the ATP binding site of S. aureus gyrase B was performed using Glide. Such compounds could be considered as promising scaffolds for the development of new potent antibacterial agents.
journal_name
Arch Pharm (Weinheim)journal_title
Archiv der Pharmazieauthors
Rizk OH,Bekhit MG,Hazzaa AAB,El-Khawass EM,Abdelwahab IAdoi
10.1002/ardp.201900086subject
Has Abstractpub_date
2019-10-01 00:00:00pages
e1900086issue
10eissn
0365-6233issn
1521-4184journal_volume
352pub_type
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