An Improved Synthesis of Key Intermediate to the Formation of Selected Indolin-2-Ones Derivatives Incorporating Ultrasound and Deep Eutectic Solvent (DES) Blend of Techniques, for Some Biological Activities and Molecular Docking Studies

We have developed a new idea to synthesize a key intermediate molecule by utilizing deep eutectic solvent (DES) and ultrasound in a multistep reaction to ensure process cost-effectiveness. To confirm the stability of reagents with DES, electronic energies were calculated at the B3LYP/6-31+G(d,p) level of theory. DES stabilized the reagents mainly due to strong intermolecular hydrogen bonding. Key intermediate (3) and final compounds (4a-n) were synthesized in a higher yield of 95% and 80%-88%, respectively. Further, final compounds (4a-n) were assessed for their anti-inflammatory, analgesic, ulcerogenic, and lipid peroxidation. The compounds 4f, 4g, 4j, 4l, and 4m showed good anti-inflammatory activity, while 4f, 4i, and 4n exhibited very good analgesic activity as compared to the standard drug. The ulcerogenicity of selected compounds was far less than the indomethacin. The ligands had also shown a good docking score (4f = -6.859 kcal/mol and 4n = -7.077 kcal/mol) as compared to control indomethacin (-6.109 kcal/mol) against the target protein COX-2. These derivatives have the potential to block this enzyme and can be used as NSAID. The state-of-art DFT theory was used to validate the lipid peroxidation mechanism of the active compounds which was in good agreement with the variations of BDEs and IP of the tested compounds.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

Molecules (Basel, Switzerland) - 25(2020), 5 vom: 02. März

Sprache:

Englisch

Beteiligte Personen:

Imran, Mohd [VerfasserIn]
Bakht, Md Afroz [VerfasserIn]
Khan, Abida [VerfasserIn]
Alam, Md Tauquir [VerfasserIn]
Anouar, El Hassane [VerfasserIn]
Alshammari, Mohammed B [VerfasserIn]
Ajmal, Noushin [VerfasserIn]
Vimal, Archana [VerfasserIn]
Kumar, Awanish [VerfasserIn]
Riadi, Yassine [VerfasserIn]

Links:

Volltext

Themen:

Analgesic
Analgesics
Anti-Inflammatory Agents, Non-Steroidal
Anti-inflammatory
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
DES
DFT
EC 1.14.99.-
EC 1.14.99.1
Indoles
Indolin-2-one
Journal Article
Lipid peroxidation
Molecular docking
Ptgs2 protein, mouse
Thiazole-indole
Ulcerogenic
Ultrasound

Anmerkungen:

Date Completed 04.12.2020

Date Revised 14.12.2020

published: Electronic

Citation Status MEDLINE

doi:

10.3390/molecules25051118

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM307226085