1-(2-Hydroxy-5-((trimethylsilyl)ethynyl)phenyl)ethanone based α,β-unsaturated derivatives an alternate to non-sulfonamide carbonic anhydrase II inhibitors, synthesis via Sonogashira coupling, binding analysis, Lipinsk’s rule validation

Mahar, Jamaluddin; Saeed, Aamer; Belfield, Kevin D.; Larik, Fayaz Ali; Channar, Pervaiz Ali; Kazi, Mehar Ali; Abbas, Qamar; Hassan, Mubashir; Raza, Hussain

doi:10.1016/j.bioorg.2018.11.031

Cited by 9 publications

(6 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the case of phenyl-substituted acyl hydrazide derivatives, an enhancement of the activity against the three isozymes was observed in compounds 28 , 29 , 30 , and 31 . While for the compounds having 3-methoxyphenyl acyl derivatives, 32 , 33 , 34 , 35 , and 36 lead to variation between the three isozymes and the enhancement or decrease in the activity of the compound depended on other substituents coming from phenyl sulfonyl chloride part [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Carbonic Anhydrase II/IX/XII Inhibition, DFT, and Molecular Docking Studies of Hydrazide-Sulfonamide Hybrids of 4-Methylsalicyl- and Acyl-Substituted Hydrazide

Khushal

Mumtaz

Shadoul

et al. 2022

BioMed Research International

View full text Add to dashboard Cite

Carbonic anhydrases (CAs and EC 4.2.1.1) are the Zn2+ containing enzymes which catalyze the reversible hydration of CO2 to carbonate and proton. If they are not functioning properly, it would lead towards many diseases including tumor. Synthesis of hydrazide-sulfonamide hybrids (19-36) was carried out by the reaction of aryl (10-11) and acyl (12-13) hydrazides with substituted sulfonyl chloride (14-18). Final product formation was confirmed by FT-IR, NMR, and EI-MS. Density functional theory (DFT) calculations were performed on all the synthesized compounds to get the ground-state geometries and compute NMR properties. NMR computations were in excellent agreement with the experimental NMR data. All the synthesized hydrazide-sulfonamide hybrids were in vitro evaluated against CA II, CA IX, and CA XII isozymes for their carbonic anhydrase inhibition activities. Among the entire series, only compounds 22, 32, and 36 were highly selective inhibitors of hCA IX and did not inhibit hCA XII. To investigate the binding affinity of these compounds, molecular docking studies of compounds 32 and 36 were carried out against both hCA IX and hCA XII. By using BioSolveIT’s SeeSAR software, further studies to provide visual clues to binding affinity indicate that the structural elements that are responsible for this were also studied. The binding of these compounds with hCA IX was highly favorable (as expected) and in agreement with the experimental data.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis, Carbonic Anhydrase II/IX/XII Inhibition, DFT, and Molecular Docking Studies of Hydrazide-Sulfonamide Hybrids of 4-Methylsalicyl- and Acyl-Substituted Hydrazide

Khushal

Mumtaz

Shadoul

et al. 2022

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Carbonic anhydrase inhibition assay . Carbonic anhydrase inhibition was measured as described previously with some modifications [53–55]. The method is based on the principle that p ‐nitrophenyl acetate is hydrolyzed by carbonic anhydrase to form yellow colored p ‐nitrophenol, which was measured spectrophotometrically.…”

Section: Methodsmentioning

confidence: 99%

Convergent synthesis of carbonic anhydrase inhibiting bi‐heterocyclic benzamides: Structure–activity relationship and mechanistic explorations through enzyme inhibition, kinetics, and computational studies

Khan

Abbasi

Aziz-Ur-Rehman

et al. 2021

Journal of Heterocyclic Chem

Self Cite

View full text Add to dashboard Cite

By using a convergent methodology, a novel series of N‐arylated 4‐yl‐benzamides containing a bi‐heterocyclic thiazole–triazole core was synthesized, and the structures of these hybrid molecules, 9a–k, were corroborated through spectral analyses. The in vitro studies of these multifunctional molecules demonstrated their potent carbonic anhydrase inhibition relative to the standard used. The kinetics mechanism was exposed by Lineweaver–Burk plots, which revealed that 9j inhibited carbonic anhydrase non‐competitively by forming an enzyme‐inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 1.2 μM. The computational study was also persuasive with the experimental results, and these molecules disclosed good results of all scoring functions and interactions, which suggested a good binding to carbonic anhydrase. So, it was predicted from the inferred results that these molecules might be considered as promising medicinal scaffolds for various diseases related to the uncontrolled production of this enzyme.

show abstract

“…[27] Certain chalcone derivatives such as 1-(2-Hydroxy-5-((trimethylsilyl)ethynyl)phenyl)ethanone based chalcones possess the ability to hinder various crucial cellular enzymes, including xanthine oxidase, aldose reductase, epoxide hydrolase, protein tyrosine kinase, and quinone reductase. [28,29] Synthetic chalcones are capable of targeting the bacteria and also have drug potentiating activities. [30] To date, thousands of chalcone derivatives have been synthesized in chemical labs by various synthetic methods shown in Figure 3.…”

Section: Introductionmentioning

confidence: 99%

“…In farming it acts as a growth regulators and for the control of diseases and harmful bugs [27] . Certain chalcone derivatives such as 1‐(2‐Hydroxy‐5‐((trimethylsilyl)ethynyl)phenyl)ethanone based chalcones possess the ability to hinder various crucial cellular enzymes, including xanthine oxidase, aldose reductase, epoxide hydrolase, protein tyrosine kinase, and quinone reductase [28,29] . Synthetic chalcones are capable of targeting the bacteria and also have drug potentiating activities [30] .…”

Section: Introductionmentioning

confidence: 99%

Chalcones As Broad‐Spectrum Antimicrobial Agents: A Comprehensive Review And Analysis Of Their Antimicrobial Activities

Nawaz,

Tajammal,

Qurashi

2023

ChemistrySelect

View full text Add to dashboard Cite

The rise of drug‐resistant microbes necessitates the development of new antimicrobial agents. Increasing resistance among multidrug‐resistant microbes has spurred research efforts to overcome drug resistance through novel scaffolds and strategies. Chalcones, distinguished by their chemical structure of 1,3‐diphenylprop‐2‐en‐1‐one, have exhibited a multifaceted array of biological activities, prominently including antimicrobial and antiviral properties. Modifying the structure by adding substituent groups to the aromatic ring enhances potency, reduces toxicity, and expands pharmacological effects. This review highlights the potential of chalcones and analogues in preventing diseases affected by diverse antibiotic resistance genes, including viruses, bacteria, fungal spores, and Plasmodiidae. Our analysis underscores the fact that a multitude of chalcone compounds effectively obstruct various molecular targets pivotal in the development of antibiotic resistance, thus rendering bacteria vulnerable to conventional antibacterial agents and potentially obliterating resistance mechanisms. Certain chalcone compounds exhibit higher activity levels compared to traditional antibiotics like vancomycin and tetracycline. Additionally, Docking and SAR studies of chalcones summarize their role in developing novel drugs. Chalcones and their derivatives demonstrate promising broad‐spectrum antimicrobial activities. Investigating structure‐activity relationships (SAR) enhances our understanding of chalcone‐based drug design, enabling the development of more effective therapeutic interventions against the pressing global health challenge of antimicrobial resistance.

show abstract

1-(2-Hydroxy-5-((trimethylsilyl)ethynyl)phenyl)ethanone based α,β-unsaturated derivatives an alternate to non-sulfonamide carbonic anhydrase II inhibitors, synthesis via Sonogashira coupling, binding analysis, Lipinsk’s rule validation

Cited by 9 publications

References 24 publications

Synthesis, Carbonic Anhydrase II/IX/XII Inhibition, DFT, and Molecular Docking Studies of Hydrazide-Sulfonamide Hybrids of 4-Methylsalicyl- and Acyl-Substituted Hydrazide

Synthesis, Carbonic Anhydrase II/IX/XII Inhibition, DFT, and Molecular Docking Studies of Hydrazide-Sulfonamide Hybrids of 4-Methylsalicyl- and Acyl-Substituted Hydrazide

Convergent synthesis of carbonic anhydrase inhibiting bi‐heterocyclic benzamides: Structure–activity relationship and mechanistic explorations through enzyme inhibition, kinetics, and computational studies

Chalcones As Broad‐Spectrum Antimicrobial Agents: A Comprehensive Review And Analysis Of Their Antimicrobial Activities

Contact Info

Product

Resources

About