Synthesis, characterization, lipoxygenase inhibitory activity and in silico molecular docking of biaryl bis(benzenesulfonamide) and indol-3-yl-hydrazide derivatives

Mutahir, Sadaf; Yar, Muhammad; Khan, Muhammad Asim; Ullah, Nisar; Shahzad, Sohail Anjum; Khan, Islam Ullah; Mehmood, Rana Atif; Ashraf, Muhammad; Nasar, Rumana; Pontiki, Eleni

doi:10.1007/s13738-014-0573-9

Cited by 4 publications

(3 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Molecular docking is a useful tool for complex interactions between the receptor and ligand. [36,37] To further investigate the binding ability and mode of compounds 1-4 to cholinesterase, molecular modeling was carried out by the Cdocker module of Discovery studio (DS, V7.6). As shown in Figures 4 -7, the docking results indicated that 1-4 could bind with the CAS, mid-gorge site and PAS of AChE.…”

Section: Docking Studiesmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Yang

Qiao

Hui

et al. 2020

Chemistry & Biodiversity

View full text Add to dashboard Cite

Four xanthone derivatives were synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) with metal chelating ability and antioxidant ability against Alzheimer's disease (AD). Most of them exhibited potential acetylcholinesterase (AChE), butylcholinesterase (BuChE) inhibitory, antioxidant and metal chelating properties. Among them, 1-hydroxy-3-[2-(pyrrolidin-1-yl)ethoxy]-9H-xanthen-9-one had the highest ability to inhibit AChE and displayed high selectivity towards AChE (IC 50 = 2.403 � 0.002 μM for AChE and IC 50 = 31.221 � 0.002 μM for BuChE), and it was also a good antioxidant (IC 50 = 2.662 � 0.003 μM). Enzyme kinetic studies showed that this compound was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Interestingly, its copper complex showed more significant inhibitory activity for AChE (IC 50 = 0.934 � 0.002 μM) and antioxidant activity (IC 50 = 1.064 � 0.003 μM). Molecular dockings were carried out for the four xanthone derivatives in order to further investigate the binding modes. Finally, the blood-brain barrier (BBB) penetration prediction indicated that all compounds might penetrate BBB. These results suggested that 1-hydroxy-3-[2-(pyrrolidin-1-yl)ethoxy]-9H-xanthen-9-one was promising AChEI with metal chelating ability and antioxidant ability for the further investigation.

show abstract

Section: Docking Studiesmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Yang

Qiao

Hui

et al. 2020

Chemistry & Biodiversity

View full text Add to dashboard Cite

show abstract

“…The biologically active Mannich bases are a structurally diverse family of chemical compounds formed by the addition of an aminomethyl functional group via the Mannich reaction, also known as amino alkylation reactions, involving active hydrogen, an amine, and an aldehyde. It has a wide range of uses in the treatment of natural macromolecules such as leather, paper, textiles, cosmetics products, analytical reagents, paint, water treatment, as an additive in the petroleum industry, and the preparation of synthetic polymers [13][14][15]. However, pharmaceutical chemistry is a significant field for Mannich bases, as evidenced by the multiple articles published on the importance and uses of this active class each year [16,17].…”

Section: Introductionmentioning

confidence: 99%

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases

Mutahir

Khan

Mushtaq³

et al. 2023

Molecules

Self Cite

View full text Add to dashboard Cite

Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment.

show abstract

“…A slight alteration in the structure of 1,3,4oxadiazole can result in both qualitative and quantitative variations in biological activities. [12 -14] It has been reported that oxadiazole derivatives inhibit aldose reductase, [15] urease, [16] thymidine phosphorylase, [17] acetylcholinesterase inhibition, [18,19] lipoxygenase inhibitors, [20,21] α-glucosidase inhibitors, [22] human DNA topoisomerase Iiα, [23] and carbonic anhydrase I, II, IX, and XII. [24] All these and other reported derivatives exhibit a broad spectrum of pharmacological activities including antituberculosis, [25] anti-Alzheimer's activity, [26] anti-inflammatory, [27] anticonvulsant and antimicrobial, [28] analgesic and antiepileptic, [29] antidiabetic, [30] cytotoxic, [31] anticancer, [32] activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, in Vitro Cholinesterase Inhibition, Molecular Docking, DFT, and ADME Studies of Novel 1,3,4‐Oxadiazole‐2‐Thiol Derivatives

Tariq

Mutahir

Khan

et al. 2022

Chemistry & Biodiversity

Self Cite

View full text Add to dashboard Cite

A series of 1,3,4-oxadiazole-2-thiol derivatives bearing various alkyl or aryl moieties were designed, synthesized, and characterized using modern spectroscopic methods to yield 17 compounds (6a-6q) that were screened for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in the search for 'lead' compounds for Alzheimer's disease treatment (AD). The compounds 6q, 6p, 6k, 6o, and 6l showed inhibitory capability against AChE and BChE, with IC 50 values ranging from 11.73 � 0.49 to 27.36 � 0.29 μM for AChE and 21.83 � 0.39 to 39.43 � 0.44 μM for BChE, inhibiting both enzymes within a limited range. The SAR ascertained that the substitution of the aromatic moiety had a profound effect on the AChE and BChE inhibitory potential as compared to the aliphatic substitutions which were supported by the molecular docking studies. The druglikeness of the most synthesized compounds was confirmed by in silico ADME investigations. These results were additionally supplemented by the molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps got from DFT calculations. ESP maps expose that on all structures, there are two potential binding sites conquered by the most positive and most negative districts.

show abstract

Synthesis, characterization, lipoxygenase inhibitory activity and in silico molecular docking of biaryl bis(benzenesulfonamide) and indol-3-yl-hydrazide derivatives

Cited by 4 publications

References 46 publications

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi‐Target Strategy

Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases

Synthesis, in Vitro Cholinesterase Inhibition, Molecular Docking, DFT, and ADME Studies of Novel 1,3,4‐Oxadiazole‐2‐Thiol Derivatives

Contact Info

Product

Resources

About