A novel class of 1,4-disubstituted 1,2,3-triazoles: Regioselective synthesis, antimicrobial activity and molecular docking studies

Rao, K. Chennakesava; Balachandran, C.; Arun, Y.; Easwaramoorthi, K.; Mahalingam, Sakkarapalayam M.; Ignacimuthu, S.; Arumugam, Natarajan; Almansour, Abdulrahman I.; Perumal, Paramasivan T.

doi:10.1016/j.arabjc.2020.10.026

Cited by 7 publications

(6 citation statements)

References 20 publications

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“…The active site of DNA gyrase (PDB: 4URO) was generated according to the previously reported method (Alotaibi & Amer, 2020; Fayed et al, 2022), where the trigonal matcher placement method was used to generate the optimized 3D structure of ligand inside the active site of pocket. Additionally, the active site topoisomerase IV (PDB: 4EMV) was obtained according to the previously reported method (Kella et al, 2020 ) , and the co‐crystalized ligand redocked inside the active site at RMSD = 0.49 Å with binding energy S = −41.74 kcal/mol. The co‐crystallized ligand exhibited five hydrogen bonds with Asp78, Asn140, Arg140, and Arg81, as well as one arene‐cation interaction with Arg81.…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, the active site topoisomerase IV (PDB: 4EMV) was obtained according to the previously reported method (Kella et al, 2020), and the co-crystalized ligand redocked inside the active site at RMSD = 0.49 Å with binding energy S = −41.74 kcal/mol. The cocrystallized ligand exhibited five hydrogen bonds with Asp78, Asn140, Arg140, and Arg81, as well as one arene-cation interaction with Arg81.…”

Section: Molecular Docking Simulationmentioning

confidence: 99%

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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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Section: Methodsmentioning

confidence: 99%

Section: Molecular Docking Simulationmentioning

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

View full text Add to dashboard Cite

show abstract

“…The active site of DNA gyrase (PDB: 4URO) was generated according to the previously reported method (Alotaibi & Amer, 2020), where the Trigonal matcher placement method was used to generate the optimized 3D structure of ligand inside the active site of pocket. Additionally, the active site topoisomerase IV (PDB: 4EMV) obtained according to the previously reported method (Kella et al, 2020), and the co‐crystalized ligand redocked inside the active site at RMSD = 0.49 °A with binding energy S = −41.74 Kcal/mol. The co‐crystallized ligand exhibited five hydrogen bonds with Asp78, Asn140, Arg140, and Arg81, as well as one arene‐cation interaction with Arg81.…”

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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“…The improvement of useful and novel construction approaches for synthesizing polycyclic-containing heterocyclic molecules has assigned a wide-ranging field of pharmaceutical chemistry [ 12 ]. Various attempts have been focused on utilizing hydrazide as a unique synthon for synthesizing five- and six-membered heterocyclic rings, and their great biological applications [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Many heterocyclic compounds possessing nitrogen and oxygen exhibit various pharmacological and biological activities involving antimicrobial, antitubercular, antitumor, anti-inflammatory, antileishmanial, serine-protease-inhibitory, and antiviral activity ( Figure 1 ) [ 16 , 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase Enzymes

Al-Ghorbani,

Alharbi,

Al-Odayni

et al. 2023

Pharmaceuticals

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Novel analogs of quinoline and isoindoline containing various heterocycles, such as tetrazole, triazole, pyrazole, and pyridine, were synthesized and characterized using FT-IR, NMR, and mass spectroscopy, and their antioxidant and antidiabetic activities were investigated. The previously synthesized compound 1 was utilized in conjugation with ketone-bearing tetrazole and isoindoline-1,3-dione to synthesize Schiff’s bases 2 and 3. Furthermore, hydrazide 1 was treated with aryledines to provide pyrazoles 4a–c. Compound 5 was obtained by treating 1 with potassium thiocyanate, which was then cyclized in a basic solution to afford triazole 6. On the other hand, pyridine derivatives 7a–d and 8a–d were synthesized using 2-(4-acetylphenyl)isoindoline-1,3-dione via a one-pot condensation reaction with aryl aldehydes and active methylene compounds. From the antioxidant and antidiabetic studies, compound 7d showed significant antioxidant activity with an EC50 = 0.65, 0.52, and 0.93 mM in the free radical scavenging assays (DPPH, ABTS, and superoxide anion radicals). It also displayed noteworthy inhibitory activity against both enzymes α-glycosidase (IC50: 0.07 mM) and α-amylase (0.21 mM) compared to acarbose (0.09 mM α-glycosidase and 0.25 mM for α-amylase), and higher than in the other compounds. During in silico assays, compound 7d exhibited favorable binding affinities towards both α-glycosidase (−10.9 kcal/mol) and α-amylase (−9.0 kcal/mol) compared to acarbose (−8.6 kcal/mol for α-glycosidase and −6.0 kcal/mol for α-amylase). The stability of 7d was demonstrated by molecular dynamics simulations and estimations of the binding free energy throughout the simulation session (100 ns).

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A novel class of 1,4-disubstituted 1,2,3-triazoles: Regioselective synthesis, antimicrobial activity and molecular docking studies

Cited by 7 publications

References 20 publications

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

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

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

Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase Enzymes

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