Pyridyl thiosemicarbazide: synthesis, crystal structure, DFT/B3LYP, molecular docking studies and its biological investigations

Abu‐Melha, Sraa

doi:10.1186/s13065-018-0469-3

Cited by 11 publications

(10 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results revealed that compound 3 showed the least energy gap (ΔE) compared with the other isolated compounds suggesting high chemical reactivity and considerable intramolecular charge transfer from electron donor (HOMO) to electron acceptor (LUMO) groups. 34 Based on this results compound 3 has better bioactivity compared with other reported compounds herein. Additionally, compound 3 has large electronegativity (χeV), global softness (σ eV −1 ), and global electrophilicity (ωeV) compared with other compounds ( Table 6 ).…”

Section: Resultsmentioning

confidence: 58%

In silico Molecular Docking, DFT Analysis and ADMET Studies of Carbazole Alkaloid and Coumarins from Roots of Clausena anisata: A Potent Inhibitor for Quorum Sensing

Eswaramoorthy¹,

Hailekiros²,

Sabir³

et al. 2021

AABC

View full text Add to dashboard Cite

Introduction In modern drug design, in silico methods are largely used to understand drug-receptor interactions and quantum chemical properties. In the present study, a computational de novo design approach was used to confirm mode of binding for antibacterial activity, elucidating quantum chemical properties and ADMET-drug-likeness of carbazole alkaloid ( 1 ) and three coumarins ( 2 – 4 ) isolated from roots of Clausena anisata . Methods Docking studies were performed with DNA-Gyrase (6F86) and LasR binding domain (2UV0) employing a flexible ligand docking approach using AutoDock Vina. SwissADME prediction and toxicological predictions were performed by ADMET. The optimized structures and molecular electrostatic potential surface of the isolated compounds were predicted by DFT analysis using B3LYP/6-31G basis levels. Results and Discussion The docking results revealed that compound 3 showed better docking scores against both DNA gyrase B and LasR binding domain compared with ciprofloxacin with potential as an inhibitor of bacterial DNA gyrase and quorum sensing LasR binding domain. The SwissADME prediction results showed that all the isolated compounds ( 1–4 ) satisfy Lipinski’s rule of five with zero violations. Toxicological prediction results suggested that all compounds and ciprofloxacin are non-hepatotoxic, non-carcinogenic, non-irritant, immunogenic, and non-cytotoxic. The DFT analysis results revealed that compound 3 has large electronegativity (χeV), global softness (σ eV −1 ), global electrophilicity (ωeV), and mutagenicity value closer to ciprofloxacin (with LD 50 value of 480 mg/kg) suggesting better bioactivity and chemical reactivity with considerable intra-molecular charge transfer between electron-donor to electron-acceptor groups. Conclusion Overall, compound 3 may serve as a lead molecule that could be developed into a potent E. coli DNA gyrase B inhibitor and efficient inhibitor for quorum sensing auto-inducer LasR binding domain of Pseudomonas aeruginosa .

show abstract

Section: Resultsmentioning

confidence: 58%

In silico Molecular Docking, DFT Analysis and ADMET Studies of Carbazole Alkaloid and Coumarins from Roots of Clausena anisata: A Potent Inhibitor for Quorum Sensing

Eswaramoorthy¹,

Hailekiros²,

Sabir³

et al. 2021

AABC

View full text Add to dashboard Cite

show abstract

“…All these factors have a significant impact on biological activity, including cell membrane permeability, metal complexation, and inter- and intra-molecular interactions. Since the thiosemicarbazides studied here formally can exist in tautomeric thione (C=S) and thiole (C–S) forms [ 24 , 25 , 55 , 56 ] ( Figure 3 ), we evaluated theoretically their relative Gibbs free energies. For this purpose, geometries of the thione and thiole forms of the thiosemicarbazides were optimized at the DFT level of theory, using the ωB97X-D functional [ 57 ] expressed in the def2-TZVP basis set [ 58 ], as implemented in the Gaussian16 program [ 59 ].…”

Section: Resultsmentioning

confidence: 99%

Antibacterial Activity of Fluorobenzoylthiosemicarbazides and Their Cyclic Analogues with 1,2,4-Triazole Scaffold

et al. 2020

View full text Add to dashboard Cite

The development of drug-resistant bacteria is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of antibacterial drugs is urgently needed. In this structure–activity relationship study, a library of ortho-, meta-, and para-fluorobenzoylthiosemicarbazides, and their cyclic analogues with 1,2,4-triazole scaffold, was created and tested for antibacterial activity against Gram-positive bacteria strains. While all tested 1,2,4-triazoles were devoid of potent activity, the antibacterial response of the thiosemicarbazides was highly dependent on substitution pattern at the N4 aryl position. The optimum activity for these compounds was found for trifluoromethyl derivatives such as 15a, 15b, and 16b, which were active against both the reference strains panel, and pathogenic methicillin-sensitive and methicillin-resistant Staphylococcus aureus clinical isolates at minimal inhibitory concentrations (MICs) ranging from 7.82 to 31.25 μg/mL. Based on the binding affinities obtained from docking, the conclusion can be reached that fluorobenzoylthiosemicarbazides can be considered as potential allosteric d-alanyl-d-alanine ligase inhibitors.

show abstract

“…The DFT calculated Mullikan’s atomic charges ( Figure 4 ) revealed charge distribution in individual atoms ( Table S4 ). 27 The HOMO, LUMO and energy gap (ΔE) of the isolated compounds are calculated and given in table. The results revealed that all the compounds have showed the least energy gap (ΔE) suggesting that high chemical reactivity and considerable intramolecular charge transfer from electron donor (HOMO) to electron acceptor (LUMO) groups ( Figure 6 ).…”

Section: Resultsmentioning

confidence: 99%

“…The results revealed that all the compounds have showed the least energy gap (ΔE) suggesting that high chemical reactivity and considerable intramolecular charge transfer from electron donor (HOMO) to electron acceptor (LUMO) groups ( Figure 6 ). 26 , 27 Additionally, compounds 8 and 9 have large electronegativity (χeV), and global electrophilicity (ωeV) compared to other compounds ( Table S3 and Figure S15 ). 27 Based on the results compounds 8 and 9 may have better bioactivity compared to other reported compounds ( 6 and 7 ) herein.…”

Section: Resultsmentioning

confidence: 99%

“… 26 , 27 Additionally, compounds 8 and 9 have large electronegativity (χeV), and global electrophilicity (ωeV) compared to other compounds ( Table S3 and Figure S15 ). 27 Based on the results compounds 8 and 9 may have better bioactivity compared to other reported compounds ( 6 and 7 ) herein.

Figure 6 Molecular orbitals and energies for the HOMO and LUMO of compounds ( 6 - 9 ).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Antibacterial, Docking, DFT and ADMET Properties Evaluation of Chalcone-Sulfonamide Derivatives Prepared Using ZnO Nanoparticle Catalysis

Weyesa¹,

Eswaramoorthy²,

Melaku³

et al. 2021

AABC

View full text Add to dashboard Cite

Introduction In the present work, two novel compounds were synthesized using zinc oxide nanoparticles through green synthesis protocol. The zinc oxide nanoparticles catalyzed reactions were afforded good to excellent yields of the target compounds 76.3–98.6%. Methodology The synthesized compounds were characterized by UV-Vis, IR and NMR. The antibacterial activity of the synthesized compounds was screened against two Gram-positive bacteria ( Bacillus cereus and Staphylococcus aureus ) and two Gram-negative bacteria ( Escherichia coli and Salmonella typhimurium ). Results and Discussion The synthesized compounds displayed potent activity against the bacterial strains. Among them, compound 8 showed strong activity against Bacillus cereus relative to the standard drug. On the other hand, compound 9 exhibited strong activity against Escherichia coli . The molecular docking study of the synthesized compounds was conducted to investigate their binding pattern with DNA gyrase and E. coli dihydropteroate synthase and all of them were found to have minimum binding energy ranging from –6.0 to −7.3 kcal/mol, and the best result achieved with compound 8 and 9 . Conclusion The findings of the in vitro antibacterial and molecular docking analysis demonstrated that the synthesized compounds have potential of antibacterial activity and can be further optimized to serve as a lead compound.

show abstract

Pyridyl thiosemicarbazide: synthesis, crystal structure, DFT/B3LYP, molecular docking studies and its biological investigations

Cited by 11 publications

References 41 publications

In silico Molecular Docking, DFT Analysis and ADMET Studies of Carbazole Alkaloid and Coumarins from Roots of Clausena anisata: A Potent Inhibitor for Quorum Sensing

In silico Molecular Docking, DFT Analysis and ADMET Studies of Carbazole Alkaloid and Coumarins from Roots of Clausena anisata: A Potent Inhibitor for Quorum Sensing

Antibacterial Activity of Fluorobenzoylthiosemicarbazides and Their Cyclic Analogues with 1,2,4-Triazole Scaffold

Antibacterial, Docking, DFT and ADMET Properties Evaluation of Chalcone-Sulfonamide Derivatives Prepared Using ZnO Nanoparticle Catalysis

Contact Info

Product

Resources

About