Synthesis, characterization, thermal properties, antimicrobial evaluation, ADMET study, and molecular docking simulation of new mono Cu (II) and Zn (II) complexes with 2-oxoindole derivatives

Ammar, Yousry A.; Ezzat, Ahmed; Mahmoud, Alaa; Mohamed, Mahmoud Basseem I.; El‐Tabl, Abdou Saad; Farag, R. S.

doi:10.1016/j.compbiomed.2022.105473

Cited by 46 publications

(29 citation statements)

References 82 publications

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“…In drug discovery research, computational docking is a very important tool to understand how synthetic compounds interact with biological targets. [ 57–59 ] In an attempt to develop potent anti‐inflammatory agents, a series of 3‐aminopyrazole derivatives 4a – c and 5a – c and pyrazolo[1,5‐ a ]pyrimidine derivatives 6 – 11 were docked against two proteins of cyclooxygenase‐1 and two cyclooxygenase‐2 using molecular operating environmental (MOE) 2014.10. Our study selected two crystal structure of cyclooxygenase‐1 (PDB: 3KK6 and 4O1Z), and two crystal structure of cyclooxygenase‐2 (PDB: 1CX2 and 3LN1) that were retrieved from protein data bank (https://www.rcsb.org/).…”

Section: Resultsmentioning

confidence: 99%

“…In drug discovery research, computational docking is a very important tool to understand how synthetic compounds interact with biological targets. [57][58][59] In an attempt to develop potent anti-inflammatory agents, in Table 1. The docking data have been compared with celecoxib and meloxicam as two reference drugs.…”

Section: Virtual Screening As Anti-inflammatory Agentsmentioning

confidence: 99%

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Discovery of novel pyrazole and pyrazolo[1,5‐a]pyrimidine derivatives as cyclooxygenase inhibitors (COX‐1 and COX‐2) using molecular modeling simulation

Ayman

Radwan

Elmetwally

et al. 2022

Archiv der Pharmazie

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Searching for effective and selective anti-inflammatory agents, our study involved designing and synthesizing new pyrazole and pyrazolo[1,5-a]pyrimidine derivatives 4-11. The structures of the synthesized derivatives were confirmed using different spectroscopic techniques. Virtual screening was achieved for the newly designed derivatives using in silico docking simulation inside the active sites of four proteins classified as two cyclooxygenases (COX)-1 (PDB: 3KK6 and 4OIZ) and two COX-2 (PBD: 1CX2 and 3LN1). Among them, six derivatives 4c, 5b, 6a, 7a, 7b, and 10b displayed the highest binding energy. These derivatives were evaluated for their in vitro COX-1 and COX-2 inhibitory activities and their selectivity indexes were calculated. Additionally, these derivatives displayed IC 50 values ranging between 4.909 ± 0.25 and 57.53 ± 2.91 µM, and 3.289 ± 0.14 and 124 ± 5.32 µM, against COX-1 and COX-2, respectively. Furthermore, the tested derivatives were found to have selective inhibitory activity on the COX-2 enzyme. Surprisingly, the two pyrazole derivatives 4c and 5b were found to be the most active, with IC 50 values of 9.835 ± 0.50 and 4.909 ± 0.25 µM and 4.597 ± 0.20 and 3.289 ± 0.14 µM compared with meloxicam (1.879 ± 0.1 and 5.409 ± 0.23 µM) and celecoxib (5.439 ± 0.28 and 2.164 ± 0.09 µM) against COX-1/-2, respectively. Besides, two pyrazole derivatives, 4c and 5b, displayed a COX-1/COX-2 SI of 2.14 and 1.49. Computational techniques such as molecular docking, density function theory (DFT) calculation, and chemical absorption, distribution, metabolism, excretion, and toxicity evaluation were applied to explain the molecules' binding mode, chemical nature, drug likeness, and toxicity prediction.

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Section: Resultsmentioning

confidence: 99%

Section: Virtual Screening As Anti-inflammatory Agentsmentioning

confidence: 99%

Discovery of novel pyrazole and pyrazolo[1,5‐a]pyrimidine derivatives as cyclooxygenase inhibitors (COX‐1 and COX‐2) using molecular modeling simulation

Ayman

Radwan

Elmetwally

et al. 2022

Archiv der Pharmazie

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“…Molecular docking study for the most active hydrazono‐quinoline and positive control (ciprofloxacin and levofloxacin) were evaluated inside the active site of DNA gyrase (PDB: 4URO) and topoisomerase IV (PDB: 4EMV) using Molecular operating Environmental (MOE) (Eldeeb et al, 2022; El‐Kalyoubi, et al, 2022; Ragab, Ammar et al, 2022; Saadon et al, 2022). Firstly, the structure of the synthesized quinoline and positive controls were built using chembiodraw 2014 and then exported to MOE (Hassan et al, 2022; Rizk et al, 2021, Rizk et al, 2020), where the hydrogen bond added, and the structure exposed to energy minimized using MMFF94x forcefield as described previously (Ezzat et al, 2022; Ibrahim et al, 2022; Khattab et al, 2022).…”

Section: Methodsmentioning

confidence: 99%

Development and radiosterilization of new hydrazono‐quinoline hybrids as DNA gyrase and topoisomerase IV inhibitors: Antimicrobial and hemolytic activities against uropathogenic isolates with molecular docking study

et al. 2022

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This study aimed to synthesize new potent quinoline derivatives based on hydrazone moieties and evaluate their antimicrobial activity. The newly synthesized hydrazono‐quinoline derivatives 2, 5a, 9, and 10b showed the highest antimicrobial activity with MIC values ≤1.0 μg/ml against bacteria and ≤8.0 μg/ml against the fungi. Further, these derivatives exhibited bactericidal and fungicidal effects with MBC/MIC and MFC/MIC ratio ≤4. Surprisingly, the most active compounds displayed good inhibition to biofilm formation with MBEC values ranging between (40.0 ± 10.0 – 230.0 ± 31.0) and (67.0 ± 24.0 – 347.0 ± 15.0) μg/ml against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. The hemolytic assays confirmed that the hydrazono‐quinoline derivatives are non‐toxic with low % lysis values ranging from 4.62% to 14.4% at a 1.0 mg/ml concentration. Besides, compound 5a exhibited the lowest hemolytic activity value of ~4.62%. Furthermore, the study suggests that the hydrazono‐quinoline analogs exert their antibacterial activity as dual inhibitors for DNA gyrase and DNA topoisomerase IV enzymes with IC50 values ranging between (4.56 ± 0.3 – 21.67 ± 0.45) and (6.77 ± 0.4 – 20.41 ± 0.32) μM, respectively. Additionally, the recent work advocated that compound 5a showed the reference SAL at the ɣ‐radiation dose of 10.0 kGy in the sterilization process without affecting its chemical structure. Finally, the in silico drug‐likeness, toxicity properties, and molecular docking simulation were performed. Besides, the result exhibited good oral‐bioavailability, lower toxicity prediction, and lower binding energy with good binding mode rather than the positive control.

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“…Hybridization is an emerging concept in drug discovery that has recently gained increased attention in the scientific community to circumvent serious drug resistance (Eldeeb et al, 2022; Fares et al, 2015; Hassan et al, 2021; Ragab, Ammar, et al, 2022). Based on the abovementioned results and continuing our recent efforts to synthesize a heterocyclic nucleus with high biological significance containing a hybrid structure (Fayed, Ammar, et al, 2021; Ragab, Elsisi, et al, 2022; Saadon et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

A new exploration toward adamantane derivatives as potential anti‐MDR agents: Design, synthesis, antimicrobial, and radiosterilization activity as potential topoisomerase IV and DNA gyrase inhibitors

Abusaif

Aboul-Magd

Wassel

et al. 2022

Drug Development Research

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Developing novel antimicrobial agents has become a necessitate due to the increasing rate of microbial resistance to antibiotics. All the newly adamantane derivatives were evaluated for their antimicrobial activities against six MDR clinical pathogenic isolates. The results exhibited that 13 compounds have from potent to good activity. Among those, five derivatives (6, 7, 9, 14a, and 14b) displayed the potent activities against the different isolates tested (MIC < 0.25 µg/ml with bacteria and <8 µg/ml with fungi) compared with Ciprofloxacin (CIP) and Fluconazole (FCA). Additionally, the potent adamantanes showed bactericidal and fungicidal effects based on (MBCs and MFCs) and the time‐kill assay. The most active adamantane derivatives 7 and 14b exhibited a synergistic effect of ΣFIC ≤ 0.5 with CIP and FCA against the bacterial and fungal isolates. Moreover, no antagonistic effect appeared for the tested derivatives. Additionally, the interaction of DNA gyrase and topoisomerase IV enzymes with the compounds 6, 7, 9, 14a, and 14b exhibited potent antimicrobial activity using in vitro biochemical assays and gel‐based DNA‐supercoiling inhibition method. The activity of DNA gyrase and topoisomerase IV enzymes showed inhibitory activity (IC50) of 6.20 µM and 9.40 µM with compound 7 and 10.14 µM and 13.28 µM with compound 14b, respectively. Surprisingly, exposing compound 7 to gamma irradiation sterilized and increased its activity. Finally, the in‐silico analysis predicted that the most active derivatives had good drug‐likeness and safe properties. Besides, molecular docking and quantum chemical studies revealed several important interactions inside the active sites and showed the structural features necessary for activity.

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Synthesis, characterization, thermal properties, antimicrobial evaluation, ADMET study, and molecular docking simulation of new mono Cu (II) and Zn (II) complexes with 2-oxoindole derivatives

Cited by 46 publications

References 82 publications

Discovery of novel pyrazole and pyrazolo[1,5‐a]pyrimidine derivatives as cyclooxygenase inhibitors (COX‐1 and COX‐2) using molecular modeling simulation

Discovery of novel pyrazole and pyrazolo[1,5‐a]pyrimidine derivatives as cyclooxygenase inhibitors (COX‐1 and COX‐2) using molecular modeling simulation

Development and radiosterilization of new hydrazono‐quinoline hybrids as DNA gyrase and topoisomerase IV inhibitors: Antimicrobial and hemolytic activities against uropathogenic isolates with molecular docking study

A new exploration toward adamantane derivatives as potential anti‐MDR agents: Design, synthesis, antimicrobial, and radiosterilization activity as potential topoisomerase IV and DNA gyrase inhibitors

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