Exploring the synthesis, structure, spectroscopy and biological activities of novel 4-benzylidene-1-(2-(2,4-dichloro phenyl)acetyl) thiosemicarbazide derivatives: An integrated experimental and theoretical investigation

Waheed, Mahnoor; Idris, Sana; Jan, Faheem; Alam, Aftab; Alam, Aftab; Ibrahim, Muhammad; AlAsmari, Abdullah F.; Alharbi, Metab; Alasmari, Fawaz; Khan, Momin

doi:10.1016/j.jsps.2023.101874

Cited by 16 publications

(2 citation statements)

References 60 publications

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“…All the density functional theory (DFT) calculations were carried out at Gaussian 09 package. The geometry optimizations were performed using a hybrid functional B3LYP with 6-311++G(d,p) basis set 42 , 43 . To further ensure the true minima, the frequency calculations were performed without imaginary frequency.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment

Gul,

Jan,

Alam

et al. 2024

Sci Rep

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A library of novel bis-Schiff base derivatives based on thiobarbituric acid has been effectively synthesized by multi-step reactions as part of our ongoing pursuit of novel anti-diabetic agents. All these derivatives were subjected to in vitro α-glucosidase inhibitory potential testing after structural confirmation by modern spectroscopic techniques. Among them, compound 8 (IC50 = 0.10 ± 0.05 µM), and 9 (IC50 = 0.13 ± 0.03 µM) exhibited promising inhibitory activity better than the standard drug acarbose (IC50 = 0.27 ± 0.04 µM). Similarly, derivatives (5, 6, 7, 10 and 4) showed significant to good inhibitory activity in the range of IC50 values from 0.32 ± 0.03 to 0.52 ± 0.02 µM. These derivatives were docked with the target protein to elucidate their binding affinities and key interactions, providing additional insights into their inhibitory mechanisms. The chemical nature of these compounds were reveal by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-311++G(d,p) basis set. The presence of intramolecular H-bonding was explored by DFT-d3 and reduced density gradient (RGD) analysis. Furthermore, various reactivity parameters were explored by performing TD-DFT at CAM-B3LYP/6-311++G(d,p) method.

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Section: Methodsmentioning

confidence: 99%

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment

Gul,

Jan,

Alam

et al. 2024

Sci Rep

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“…Moreover, molecular docking and molecular dynamic simulation studies [55] were executed to forecast the binding conformations of the ligands within the binding site of the target protein and suggested the stability of the most active compounds at the target protein's binding site. This effort to comprehend the binding properties assumes paramount significance in the domain of drug design, furnishing invaluable insights into fundamental biochemical processes [56] . This exhaustive pharmacological exploration is positioned not only to aid researchers in pinpointing the most efficacious compound for subsequent drug development but also to substantially contribute to the progression of pharmaceutical science.…”

Section: Introductionmentioning

confidence: 99%

“Synergistic Innovation: Crafting Indazole Derivatives for Advanced Anticancer, Antioxidant, and Antimicrobial Efficacy through Integrative Design and Holistic Evaluation”

Yadav,

Pal,

Purawarga Matada

et al. 2024

ChemistrySelect

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This study presents the synthesis and characterization of a newer series of N‐(1‐(2‐(phenylamino) pyrimidin‐4‐yl)‐1H‐indazol‐5‐yl)benzenesulfonamide (6 a–6 n) and N‐(6‐ethoxy‐1‐(2‐(phenylamino) pyrimidin‐4‐yl)‐1H‐indazol‐5‐yl)benzenesulfonamide (7 a–7 c) derivatives through the reaction of N‐(1‐(2‐chloropyrimidin‐4‐yl)‐1H‐indazol‐5‐yl) benzenesulfonamide (4 a–i) and N‐(1‐(2‐chloropyrimidin‐4‐yl)‐6‐ethoxy‐1H‐indazol‐5‐yl) benzenesulfonamide (5 a–i) with various aniline derivatives in isopropanol. The compounds were thoroughly evaluated for their biological activities, encompassing antifungal, antibacterial, and anticancer assays, as well as antioxidant potential in DPPH and ABTS assays. Compound 7 b (IC50: 0.0125 MIC), 6 e (IC50: 0.0128 MIC), and 6 i (IC50: 0.0128 MIC) demonstrated exceptional antibacterial efficacy, while 6 d (IC50: 0.0124 MIC), 6 f (IC50: 0.0125 MIC) and 7 c (IC50: 0.0118 MIC), exhibited notable antifungal activity. Compounds 6 c (IC50: 13.31±0.32 μM, A459) & (IC50: 22.36±1.76 μM, MCF7) displayed significant anticancer activity comparable to established drugs. Moreover, 6 b (IC50: 11.22±0.16 μM, A459) & (IC50: 18.21±1.32 μM, MCF7) and 6 d (IC50: 11.23±0.17 μM, A459) & (IC50: 18.31±1.41 μM, MCF7) showed remarkable anticancer potency. Notably, compound N‐(1‐(2‐(methyl(phenyl)amino)pyrimidin‐4‐yl)‐1H‐indazol‐5‐yl)‐4‐nitrobenzenesulfonamide (IC50:0.1090 μmol/mL for DPPH and IC50: 0.1286 μmol/mL for ABTS) exhibited the most significant antioxidant activity. Computational docking studies revealed robust binding interactions with target enzymes (PDB ID: 4JT3 for anticancer, PDB ID: 1EA1 for antifungal, PDB ID: 1KZN for antibacterial, PDB ID: 3SRG for antioxidant), supported by molecular dynamics simulations indicating consistent stability of the most potent compound within the binding sites of the target proteins. These findings underscore the therapeutic potential of these derivatives, warranting further investigation for potential clinical applications.

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Designing and Synthesis of Novel Fexofenadine‐Derived Hydrazone‐Schiff Bases as Potential Urease Inhibitors: In‐Vitro, Molecular Docking and DFT Investigations

Ayaz,

Alam,

Zainab

et al. 2024

Chemistry & Biodiversity

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Thirteen novel hydrazone‐Schiff bases (3‐15) of fexofenadine were succesfully synthesized, structurally deduced and finally assessed their capability to inhibit urease enzyme (in vitro). In the series, six compounds 12 (IC50 = 10.19 ± 0.16 µM), 11 (IC50 = 15.05 ± 1.11 µM), 10 (IC50 = 17.01 ± 1.23 µM), 9 (IC50 = 17.22 ± 0.81 µM), 13 (IC50 = 19.31 ± 0.18 µM), and 14 (IC50 = 19.62 ± 0.21 µM) displayed strong inhibitory action better than the standard thiourea (IC50 = 21.14 ± 0.24 µM), while the remaining compounds displayed significant to less inhibition. LUMO and HOMO showed the transferring of charges from molecules to biological transfer and MEP map showed the chemically reactive zone appropriate for drug action are calculated using DFT. AIM charges, non‐bonding orbitals, and ELF are also computed. The urease protein binding analysis benefited from the docking studies.

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Exploring the synthesis, structure, spectroscopy and biological activities of novel 4-benzylidene-1-(2-(2,4-dichloro phenyl)acetyl) thiosemicarbazide derivatives: An integrated experimental and theoretical investigation

Cited by 16 publications

References 60 publications

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment

“Synergistic Innovation: Crafting Indazole Derivatives for Advanced Anticancer, Antioxidant, and Antimicrobial Efficacy through Integrative Design and Holistic Evaluation”

Designing and Synthesis of Novel Fexofenadine‐Derived Hydrazone‐Schiff Bases as Potential Urease Inhibitors: In‐Vitro, Molecular Docking and DFT Investigations

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