Identification and molecular modeling of new quinolin-2-one thiosemicarbazide scaffold with antimicrobial urease inhibit
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ORIGINAL ARTICLE
Identification and molecular modeling of new quinolin‑2‑one thiosemicarbazide scaffold with antimicrobial urease inhibitory activity Mohammed A. I. Elbastawesy1 · Yaseen A. M. M. El‑Shaier2 · Mohamed Ramadan1 · Alan B. Brown3 · Ashraf A. Aly4 · Gamal El‑Din A. Abuo‑Rahma5 Received: 10 August 2019 / Accepted: 29 November 2019 © Springer Nature Switzerland AG 2020
Abstract A new series of 6-substituted quinolin-2-one thiosemicarbazides 6a–j has been synthesized. The structure of the target compounds was proved by different spectroscopic and elemental analyses. All the designed final compounds were evaluated for their in vitro activity against the urease-producing R. mucilaginosa and Proteus mirabilis bacteria as fungal and bacterial pathogens, respectively. Moreover, all compounds were in vitro tested as potential urease inhibitors using the cup-plate diffusion method. Compounds 6a and 6b were the most active with (IC50 = 0.58 ± 0.15 and 0.43 ± 0.09 µM), respectively, in comparison with lead compound I (IC50 = 1.13 ± 0.00 µM). Also, the designed compounds were docked into urease proteins (ID: 3LA4 and ID: 4UBP) using Open E ye® software to understand correctly about ligand–receptor interactions. The docking results revealed that the designed compounds can interact with the active site of the enzyme through multiple strong hydrogen bonds. Moreover, rapid overlay of chemical structures’ analysis was described to understand the 3D QSAR of synthesized compounds as urease inhibitors. The results emphasize the importance of polar thiosemicarbazide directly linked to 6-substituted quinolone moieties as promising antimicrobial urease inhibitors.
* Ashraf A. Aly [email protected] * Gamal El‑Din A. Abuo‑Rahma [email protected] 1
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
2
Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Sadat‑City, Menufia, Egypt
3
Chemistry Department, Florida Institute of Technology, Melbourne, FL 32901, USA
4
Department of Chemistry, Faculty of Science, Minia University, El‑Minia 61519, Egypt
5
Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, El‑Minia 61519, Egypt
13
Vol.:(0123456789)
Molecular Diversity
Graphic abstract left arm O2N
S HN N
HN
O
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ring enlargmnet N H
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H N
N O
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I Reported compound IC50 = 1.13 ± 0.00µM
II Reported compound IC50 = 16.4 ± 0.8µM
-Thiosemicarbazide -Ring modification with keeping amid -Aryl replacment -Substituent on the aryl ring R1
liker H N
left arm HN
Ar = Phenyl, benzyl, allyl R1 = EDG, WEG
S N H
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Keywords Molecular docking · ROCS analysis · R. mucilaginosa · Proteus mirabilis · Hybridization
Introduction Nitrogen containing heterocycles are important structural units in medicinal chemistry. Among various heterocyclic compounds, quinolines have gained the largest attention. Througho
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