Targeting PPAR-γ to design and synthesize antidiabetic thiazolidines

Sawant, Ramesh L.; Wadekar, Jyoti B.; Kharat, Santosh B; Makasare, Hitakshi S

doi:10.17179/excli2018-1325

Cited by 2 publications

(1 citation statement)

References 13 publications

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“…Several heterocyclic compounds have been observed to have a significant role in the chemotherapy of malignancy. 18 Although 2,4-dioxothiazolidines have been reported to be a potential platform because they are known to stimulate the PPARγ 19 receptor, they also have multiple PPARγ independent effects, and the dose required for anticancer activity of 2,4-dioxothiazolidines is significantly lower than that required for hypoglycemic activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antioxidant Studies of 2,4-Dioxothiazolidine-5-acetic Acid Based Organic Salts: SC-XRD and DFT Approach

Mashhadi,

Bhatti,

Jabeen

et al. 2023

ACS Omega

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In the current study, two organic salts (1 and 2) are synthesized, and then crystalline structures are characterized by FTIR, UV spectroscopy, and X-ray crystallographic studies. The organic salts 1 and 2 are optimized at the M06/6-311G(d,p)level of theory and further utilized for analysis of natural bond orbitals (NBOs), natural population, frontier molecular orbitals (FMOs), and global reactivity parameters, which confirmed the stability of the studied compounds and charge transfer phenomenon in the studied compounds. The studies further revealed that 1 and 2 are more stable than 3. The lowest energy merged monomer–coformer conformations were docked as flexible ligands with rigid fungal proteins and DNA receptors. The stagnant binding of the monomer through two H bonds with protein was observed for ligands 1 and 3 while different pattern was found with 2. The coformers formed a single H bond with the active site in 2 and 3 and a single pi–arene H interaction in 1. The two-point ligand–receptor interactions hooked the monomer between DNA base pairs for partial intercalation; pi stacking with additive hydrogen bonding with the base pair led to a strong benzimidazole interaction in 1 and 2, whereas ethylene diamine formed weak H bonding. Thus, the molecular docking predicted that the coformer exhibited DNA intercalation reinforced by its salt formation with benzimidazole 1 and methyl benzimidazole 2. Antioxidant studies depicted that 3 has a higher IC50 value than that of 2,4-D and also the largest value among the studied compounds, whereas 2 showed the lowest value among the studied compounds.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Antioxidant Studies of 2,4-Dioxothiazolidine-5-acetic Acid Based Organic Salts: SC-XRD and DFT Approach

Mashhadi,

Bhatti,

Jabeen

et al. 2023

ACS Omega

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Impact of Molecular Symmetry/Asymmetry on Insulin-Sensitizing Treatments for Type 2 Diabetes

et al. 2022

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Although the advantages and disadvantages of asymmetrical thiazolidinediones as insulin-sensitizers have been well-studied, the relevance of symmetry and asymmetry for thiazolidinediones and biguanides has scarcely been explored. Regarding symmetrical molecules, only one thiazolidinedione and no biguanides have been evaluated and proposed as an antihyperglycemic agent for treating type 2 diabetes. Since molecular structure defines physicochemical, pharmacological, and toxicological properties, it is important to gain greater insights into poorly investigated patterns. For example, compounds with intrinsic antioxidant properties commonly have low toxicity. Additionally, the molecular symmetry and asymmetry of ligands are each associated with affinity for certain types of receptors. An advantageous response obtained in one therapeutic application may imply a poor or even adverse effect in another. Within the context of general patterns, each compound must be assessed individually. The current review aimed to summarize the available evidence for the advantages and disadvantages of utilizing symmetrical and asymmetrical thiazolidinediones and biguanides as insulin sensitizers in patients with type 2 diabetes. Other applications of these same compounds are also examined as well as the various uses of additional symmetrical molecules. More research is needed to exploit the potential of symmetrical molecules as insulin sensitizers.

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Targeting PPAR-γ to design and synthesize antidiabetic thiazolidines

Cited by 2 publications

References 13 publications

Synthesis and Antioxidant Studies of 2,4-Dioxothiazolidine-5-acetic Acid Based Organic Salts: SC-XRD and DFT Approach

Synthesis and Antioxidant Studies of 2,4-Dioxothiazolidine-5-acetic Acid Based Organic Salts: SC-XRD and DFT Approach

Impact of Molecular Symmetry/Asymmetry on Insulin-Sensitizing Treatments for Type 2 Diabetes

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