Synthesis, biological evaluation and molecular docking studies of novel 3,5-disubstituted 2,4-thiazolidinediones derivatives

• Published in: Bioorganic chemistry Vol. 89; p. 102993
• Main Authors: Ranjan Srivastava, Alok, Bhatia, Rohit, Chawla, Pooja
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.08.2019; Elsevier
• Subjects: Anti diabetic; Anti inflammatory; Anti oxidant; Biochemistry & Molecular Biology; Chemistry; Chemistry, Organic; Docking; Life Sciences & Biomedicine; Physical Sciences; Science & Technology; Structure activity relationship; Thiazolidinedione; Docking; Structure activity relationship; Anti diabetic; Anti oxidant; Anti inflammatory; Thiazolidinedione; OXIDATIVE STRESS; ACTIVATED RECEPTOR-GAMMA; FREE-RADICALS; ANTIDIABETIC ACTIVITY; INFLAMMATION; PPAR-GAMMA; ROSIGLITAZONE; DYSFUNCTION; EXPRESSION
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.102993

[Display omitted] •The manuscript describes the simple synthetic protocol towards potent multiple-action 2,4-thiazolidinedione derivatives.•The corroboration of the pharmacological activity with in-silico evaluation has also been reported.•The compounds are promising dual action or even triple action drug candidates.•Free radicals responsible for inflammation can be curbed thus tackling inflammation. A series of thirteen novel 2,4-thiazolidinedione derivatives were synthesized through three step reaction procedure. The title compounds were synthesized by Knoevenagel condensation at the 5th position of the 2,4-thiazolidinedione ring. Various physicochemical and spectral studies were conducted to characterize the synthesized derivatives including- IR, Mass, 1H NMR, 13C NMR and elemental analysis. The derivatives were screened for in vivo anti diabetic, in vivo anti-inflammatory and in vitro free radical scavenging activities by carrageenan induced rat paw edema method, alloxan induced diabetes in wistar rats method and FRAP (ferric reducing antioxidant power) method respectively. Some of the derivatives emerged out as potent antidiabetic, anti inflammatory and free radical scavenging agents. Molecular docking was carried out to investigate some possible structural insights into the potential binding patterns of the most potent anti-diabetic molecules NB7,NB12 and NB13 with the active sites of target PPARγ (PDB ID: 2PRG) using MOE software. Dichloro derivative compound NB-7 has shown great potential in the present study as it not only has maximum antidiabetic activity but also possess excellent anti-inflammatory and antioxidant potential.