Sulphonamide and sulphonyl-hydrazone cyclic imide derivatives: Antinociceptive activity, molecular modeling and In Silico ADMET screening

Oliveira, Kely Navakoski de; Souza, M M; Sathler, P.C; Magalhães, Uiaran O.; Rodrigues, Carlos Rangel; Castro, Helena C.; Palm, Patrícia R.; Sarda, Maicon; Perotto, Pablo E.; Cezar, Sabrina; Brito, Monique Araújo de; Ferreira, Ariane S. S. R.; Cabral, Lúcio Mendes; Machado, Clodoaldo; Nunes, Ricardo José

doi:10.1007/s12272-012-1002-1

Cited by 24 publications

(9 citation statements)

References 43 publications

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“…blood) and Pgp inhibition [ 55 ]. Bioactivity of synthesized compounds was predicted by Molinspiration ( http://www.molinspiration.com/ ) online tool kit [ 56 ] and toxicity parameters like mutagenicity, tumorigenicity irritating effects and reproductive effects were computed by OSIRIS property explorer [ 57 ].…”

Section: Methodsmentioning

confidence: 99%

Synthesis, molecular docking and molecular dynamic simulation studies of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives as antidiabetic agents

et al. 2020

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A series of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives (5a-5v) has been synthesized and confirmed by physicochemical(R f , melting point) and spectral means (IR, 1 HNMR, 13 CNMR). The results of in vitro antidiabetic study against α-glucosidase indicated that compound 5o bearing 2-CH 3-5-NO 2 substituent on phenyl ring was found to be the most active compound against both enzymes. The electron donating (CH 3) group and electron withdrawing (NO 2) group on a phenyl ring highly favoured the inhibitory activity against these enzymes. The docking simulations study revealed that these synthesized compounds displayed hydrogen bonding, electrostatic and hydrophobic interactions with active site residues. The structure activity relationship studies of these compounds were also corroborated with the help of molecular modeling studies. Molecular dynamic simulations have been done for top most active compound for validating its α-glucosidase and α-amylase inhibitory potential, RMSD analysis of ligand protein complex suggested the stability of top most active compound 5o in binding site of target proteins. In silico ADMET results showed that synthesized compounds were found to have negligible toxicity, good solubility and absorption profile as the synthesized compounds fulfilled Lipinski's rule of 5 and Veber's rule.

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Section: Methodsmentioning

confidence: 99%

Synthesis, molecular docking and molecular dynamic simulation studies of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives as antidiabetic agents

et al. 2020

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“…The drug-resemblance of the derived variants was evaluated using Molinspiration online toolkit [48] and OSIRIS property explorer. [67] Lipinski's rule of five [47] states that a chemical is regarded to be a drug if it has a molecular weight of 500 Daltons or less, lower than 5 hydrogen bond donors, a log P value of no greater than 5, and lower than 10 hydrogen bond acceptors. Violation of more than two of these criteria may indicate potential bioavailability issues.…”

Section: Drug Likeness Parametersmentioning

confidence: 99%

Exploration of N‐(6‐Indazolyl) benzenesulfonamide Derivatives as Potential Antioxidants and Antimicrobial Agents: Integrating Synthesis, In Silico Docking, and Bioactivity Profiling

Yadav,

Rao,

Kumar

et al. 2023

ChemistrySelect

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A new series of N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl) benzenesulfonamide derivatives (4 a–i) and N‐(1‐(2‐chloropyrimidin‐4‐yl)‐6‐ethoxy‐1H‐indazol‐5‐yl) benzenesulfonamide derivatives (5 a–i) was synthesized via reduction of 1‐(2‐halopyrimidin‐4‐yl)‐5‐nitro‐1H‐indazole (3) with SnCl2 followed by reaction with various aryl sulphonyl chlorides in pyridine. The structures were confirmed using IR, 1H‐NMR, 13C‐NMR, and mass spectral methods. Compounds 4 a–i and 5 a–i were evaluated for antifungal and antibacterial activities against Gram‐negative and Gram‐positive bacteria. They also exhibited antioxidant potential in DPPH (IC50=0.094‐0.467 μmol/ml) and ABTS assays (IC50=0.101–0.496 μmol/ml). Remarkably, N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl)‐2‐nitrobenzenesulfonamide displayed the highest antibacterial activity, while N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl)‐4‐methoxybenzenesulfonamide showed excellent antifungal potential. Compound N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl)‐2‐nitrobenzenesulfonamide exhibited the most significant antioxidant activity. In this study, molecular dynamics simulations were utilized to rigorously examine the stability of ligand‐protein complexes, demonstrating a consistent and robust binding of the most potent compound within the target proteins′ binding sites. Computational assessments were further employed to predict the drug‐likeness and ADMET properties of the synthesized compounds. The results unequivocally confirmed the remarkable antioxidant and antimicrobial potential of all derivatives, a finding substantiated by comprehensive molecular docking analyses that revealed intricate interactions involving hydrogen bonds, electrostatic forces, and hydrophobic contacts. These findings collectively provide invaluable insights into the complex molecular structure and receptor target site dynamics, laying a strong foundation for the development of novel active antioxidant and antimicrobial agents with promising pharmaceutical implications.

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“…Sulfonylhydrazones (SH) are organic compounds described as nonclassical isosteres of acylhydrazones (NA) and considered as privileged structures. − The synthesis and applications of SH are widely explored in medicinal chemistry due to their different biological and pharmacological properties, such as antinociceptive, − antiasthmatic, antioxidant, antibacterial, , antidepressant, antineoplastic, − and antidiabetic …”

Section: Introductionmentioning

confidence: 99%

Methyl Effect on the Metabolism, Chemical Stability, and Permeability Profile of Bioactive N-Sulfonylhydrazones

et al. 2022

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Sulfonylhydrazones are privileged structures with multifaceted pharmacological activity. Exploring the hypoglycemic properties of these organic compounds, we previously revealed a new series of Nsulfonylhydrazones (NSH) as antidiabetic drug candidates. Here, we evaluated the microsomal metabolism, chemical stability, and permeability profile of these NSH prototypes, focusing on the pharmacokinetic differences in N-methylated and non-N-methylated analogs. Our results demonstrated that the N-methylated analogs (LASSBio-1772 and LASSBio-1774) were metabolized by CYP, forming three and one metabolites, respectively. These prototypes exhibited chemical stability at pH 2.0 and 7.4 and brain penetration ability. On the other hand, non-Nmethylated analogs (LASSBio-1771 and LASSBio-1773) were hydrolyzed in acid pH and could not cross the artificial blood−brain barrier. The cyano group in LASSBio-1771 was postulated as a possible site of interaction with the heme group, potentially inhibiting CYP enzymes. Moreover, prototypes with the methyl ester group were metabolized by carboxylesterase, and non-N-methylated analogs did not show oxidative metabolism. The prototypes (except LASSBio-1774) showed excellent gastrointestinal absorption. Altogether, our data support the idea that the methyl effect on NSH strongly alters their pharmacokinetic profile, enhances the recognition by CYP enzymes, promotes brain penetration, and plays a protective effect upon acid hydrolysis.

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Sulphonamide and sulphonyl-hydrazone cyclic imide derivatives: Antinociceptive activity, molecular modeling and In Silico ADMET screening

Cited by 24 publications

References 43 publications

Synthesis, molecular docking and molecular dynamic simulation studies of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives as antidiabetic agents

Synthesis, molecular docking and molecular dynamic simulation studies of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives as antidiabetic agents

Exploration of N‐(6‐Indazolyl) benzenesulfonamide Derivatives as Potential Antioxidants and Antimicrobial Agents: Integrating Synthesis, In Silico Docking, and Bioactivity Profiling

Methyl Effect on the Metabolism, Chemical Stability, and Permeability Profile of Bioactive N-Sulfonylhydrazones

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