GPR119 agonists: Novel therapeutic agents for type 2 diabetes mellitus

Manaithiya, Ajay; Alam, Ozair; Sharma, Vrinda; Naim, Mohd. Javed; Mittal, Shruti; Khan, Imran

doi:10.1016/j.bioorg.2021.104998

Cited by 20 publications

(14 citation statements)

References 153 publications

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“…G‐protein coupled receptor 119 (GPR 119) agonists have emerged as a new target for drug development for type‐2 diabetes Mellitus. [ 124 ] In an effort to identify a potent and oral GPR 119 agonist, Pola and co‐workers carried out the design and synthesis of novel series of benzylidene TZD derivatives ( 73–75 , Figure 42). The synthesized compounds were subjected to in vitro GRP119 antagonistic evaluation using cAMP assay taking AR231453 as a positive control.…”

Section: Biological Spectrum Of Tzdsmentioning

confidence: 99%

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The medicinal perspective of 2,4‐thiazolidinediones based ligands as antimicrobial, antitumor and antidiabetic agents: A review

Singh

Kajal

Pradhan

et al. 2022

Archiv der Pharmazie

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2,4-Thiazolidinedione (2,4-TZD), commonly known as glitazone, is a ubiquitous heterocyclic pharmacophore possessing a plethora of pharmacological activities and offering a vast opportunity for structural modification. The diverse range of biological activities endowed with a novel mode of action, low cost, and easy synthesis has attracted the attention of medicinal chemists. Several researchers have integrated the TZD core with different structural fragments to develop a wide range of lead molecules against various clinical disorders. The most common sites for structural modifications at the 2,4-TZD nucleus are the N-3 and the active methylene at C-5. The review covers the recent development of TZD derivatives such as antimicrobial, anticancer, and antidiabetic agents. Various 2,4-TZD based agents or drugs, which are either under clinical development or in the market, are discussed in the study. Different synthetic methodologies for synthesizing the 2,4-TZD core are also included in the manuscript.The importance of various substitutions at N-3 and C-5 and the mechanisms of action and structure-activity relationships are also discussed. We hope this study will serve as a valuable tool for the scientific community engaged in the structural exploitation of the 2,4-TZD core for developing novel drug m\olecules for life-threatening ailments.

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Section: Biological Spectrum Of Tzdsmentioning

confidence: 99%

“…Mellitus. [124] In an effort to identify a potent and oral GPR 119 agonist, Pola and co-workers carried out the design and synthesis of novel series of benzylidene TZD derivatives (73-75, Figure 42). The synthesized compounds were subjected to in vitro GRP119…”

Section: C-5 Substituted Tzdsmentioning

confidence: 99%

The medicinal perspective of 2,4‐thiazolidinediones based ligands as antimicrobial, antitumor and antidiabetic agents: A review

Singh

Kajal

Pradhan

et al. 2022

Archiv der Pharmazie

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“…A clinical study in dyslipidemia patients demonstrated that administration of GSK1292263 enhanced plasma HDL-cholesterol levels and significantly reduced LDL-cholesterol and triglyceride levels compared to placebo [ 107 ]. The detrimental effect of the decrease in oxidative/metabolic capacity warrants more studies before GPR119 agonists can treat metabolic diseases [ 104 , 108 , 109 , 110 ].…”

Section: Lipid Metabolitesmentioning

confidence: 99%

Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases

Strassheim

Sullivan

Irwin

et al. 2021

Cells

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G protein-coupled receptors (GPCRs) have originally been described as a family of receptors activated by hormones, neurotransmitters, and other mediators. However, in recent years GPCRs have shown to bind endogenous metabolites, which serve functions other than as signaling mediators. These receptors respond to fatty acids, mono- and disaccharides, amino acids, or various intermediates and products of metabolism, including ketone bodies, lactate, succinate, or bile acids. Given that many of these metabolic processes are dysregulated under pathological conditions, including diabetes, dyslipidemia, and obesity, receptors of endogenous metabolites have also been recognized as potential drug targets to prevent and/or treat metabolic and cardiovascular diseases. This review describes G protein-coupled receptors activated by endogenous metabolites and summarizes their physiological, pathophysiological, and potential pharmacological roles.

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“…Type 2 diabetes mellitus (T2DM) accounts for nearly 90% of diabetes mellitus (DM) worldwide and is a chronic metabolic disorder characterized by hyperglycemia which is triggered by dysfunction of insulin secretion or insulin resistance (Tiwari et al, 2014;Manaithiya et al, 2021). Current clinical antidiabetic drugs, including sulfonylureas and glucagon-like peptide (GLP-1) receptor agonists, increase insulin secretion via different pharmacological mechanism.…”

Section: Introductionmentioning

confidence: 99%

Microbial biotransformation to obtain stilbene methylglucoside with GPR119 agonistic activity

Huan

Chen

et al. 2023

Front. Microbiol.

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IntroductionLimitation of pharmaceutical application of resveratrol (RSV) and piceatannol (PIC) continue to exist, there is a need to obtain the superior analogs of two stilbenes with promoted activity, stability, and bioavailability. Microbial transformation has been suggested as a common and efficient strategy to solve the above problems.MethodsIn this study, Beauveria bassiana was selected to transform RSV and PIC. LC-MS and NMR spectroscopies were used to analyze the transformed products and identify their structures. The biological activities of these metabolites were evaluated in vitro with GPR119 agonist and insulin secretion assays. Single factor tests were employed to optimize the biotransformation condition.ResultsThree new methylglucosylated derivatives of PIC (1–3) and two known RSV methylglucosides (4 and 5) were isolated and characterized from the fermentation broth. Among them, 1 not only showed moderate GPR119 agonistic activity with 65.9%, but also promoted insulin secretion level significantly (12.94 ng/mg protein/hour) at 1 μM. After optimization of fermentation conditions, the yield of 1 reached 45.53%, which was increased by 4.2-fold compared with the control.DiscussionOur work presents that 3-O-MG PIC (1), obtained by microbial transformation, is an effective and safer ligand targeting GPR119, which lays a foundation for the anti-diabetic drug design in the future.

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GPR119 agonists: Novel therapeutic agents for type 2 diabetes mellitus

Cited by 20 publications

References 153 publications

The medicinal perspective of 2,4‐thiazolidinediones based ligands as antimicrobial, antitumor and antidiabetic agents: A review

The medicinal perspective of 2,4‐thiazolidinediones based ligands as antimicrobial, antitumor and antidiabetic agents: A review

Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases

Microbial biotransformation to obtain stilbene methylglucoside with GPR119 agonistic activity

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