Design, synthesis, kinetic, molecular dynamics, and hypoglycemic effect characterization of new and potential selective benzimidazole derivatives as Protein Tyrosine Phosphatase 1B inhibitors

Campos-Almazán, Mara Ibeth; Flores-Ramos, Miguel; Hernández‐Campos, Alicia; Castillo, Rafael; Sierra-Campos, Erick; Torgeson, Kristiane R.; Peti, Wolfgang; Valdez-Solana, Mónica; Oria-Hernández, Jesús; Méndez, Sara T.; Castillo-Villanueva, Adriana; Jesús, Hugo Jiménez-de; Avitia-Domínguez, Claudia; Téllez‐Valencia, Alfredo

doi:10.1016/j.bmc.2021.116418

Cited by 4 publications

(9 citation statements)

References 77 publications

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“…PT2 compound was de the most potent inhibiting PTP1B practically at 100 % and PT4 compound was the lowest with no effect on PTP1B (Table 3). Interestingly, from this chemical library a benzimidazole derivative was selected (PT3) shown a PTP1B inhibition which is in accordance with that had been reported previously [9,16] . From these data PT2 compound was selected for further characterization.…”

Section: Resultssupporting

confidence: 73%

“…Interestingly, from this chemical library a benzimidazole derivative was selected (PT3) shown a PTP1B inhibition which is in accordance with that had been reported previously. [9,16] From these data PT2 compound was selected for further characterization. First, the concentration that inhibits 50 % of enzyme (IC 50 ) activity was determined varying compound concentration, obtaining a value of 9 μM (Figure 2).…”

Section: Inhibition Assays Of Pt1-pt6 Compounds In Ptp1bmentioning

confidence: 99%

“…Purification of PTP1B was carried out according to the protocol published. [9] Briefly, transformed cells were inoculated in 500 mL Luria Bertani medium supplemented with Kanamycin 50 μg/mL, following an incubation at 37 °C, overexpression was induced with Isopropyl-β-D-thiogalactopyranoside (IPTG) 1 mM once the culture reached an OD 600 of 0.9 and incubating for 4 h more. Cells were harvested, lysed by sonication, and centrifuged.…”

Section: Purification Of Recombinant Ptp1bmentioning

confidence: 99%

“…[6] Within the role of PTP1B in Diabetes Mellitus (DM), a relationship between the overexpression of this protein and the decrease in the translocation of the insulin-sensitive GLUT4 channel has been proposed, [4] additionally, PTP1B knockout mice generated a greater sensitivity to insulin and a lower tendency to obesity, [7] and several studies report a hypoglycemic effect. [2,4,8,9] These antecedents demonstrate the relevant role of PTP1B in glucose metabolism justifying its use as a therapeutic target that can be regulated or inhibited. In the last decade, different selective or potential selective PTP1B inhibitors have been reported, [4,6,[8][9][10][11][12] which could have therapeutic use in prediabetic or DM patients.…”

Section: Introductionmentioning

confidence: 99%

“…PTP1B is widely expressed in body tissues such as liver, muscle, brain and adipose tissue [6] . Within the role of PTP1B in Diabetes Mellitus (DM), a relationship between the overexpression of this protein and the decrease in the translocation of the insulin‐sensitive GLUT4 channel has been proposed, [4] additionally, PTP1B knockout mice generated a greater sensitivity to insulin and a lower tendency to obesity, [7] and several studies report a hypoglycemic effect [2,4,8,9] . These antecedents demonstrate the relevant role of PTP1B in glucose metabolism justifying its use as a therapeutic target that can be regulated or inhibited.…”

Section: Introductionmentioning

confidence: 99%

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Development of Tyrosine Phosphatase 1B Inhibitors Based on Molecular Docking, Kinetics, and Toxicity Studies

Téllez‐Valencia,

Hernández‐Ortiz,

Guadalupe López Lujano

et al. 2023

ChemistrySelect

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Protein Tyrosine Phosphatase 1B (PTP1B) is a protein that contributes to the development of diseases that affect millions of people worldwide. In the last five years, several studies have been carried out to develop a drug that is capable of inhibiting the functions of this protein that are related to chronic degenerative diseases and obesity. In this study, we used PTP1B as a therapeutic target to perform a molecular docking to identify compounds that specifically bind to the PTP1B human protein. After molecular docking from over 500,000 compounds, we selected the six with the highest binding score and evaluated their inhibitory effect in in vitro assays. The data showed that PT2 compound was the most potent with an IC50 value of 9 μM and a noncompetitive inhibition mechanism. According to molecular docking, this compound made specific interactions in the catalytic domain of PTP1B, that could be responsible for their inhibition capability. Furthermore, cytotoxic studies in MCF‐7 cells indicated that it could be safe for humans. Therefore, PT2 compound may be a promising new drug to attend the diseases where PTP1B has functions.

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Section: Resultssupporting

confidence: 73%

Section: Inhibition Assays Of Pt1-pt6 Compounds In Ptp1bmentioning

confidence: 99%

Section: Purification Of Recombinant Ptp1bmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of Tyrosine Phosphatase 1B Inhibitors Based on Molecular Docking, Kinetics, and Toxicity Studies

Téllez‐Valencia,

Hernández‐Ortiz,

Guadalupe López Lujano

et al. 2023

ChemistrySelect

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Recent updates on development of protein-tyrosine phosphatase 1B inhibitors for treatment of diabetes, obesity and related disorders

Singh

Grewal

Grover

et al. 2022

Bioorganic Chemistry

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A Review on Benzimidazole Heterocyclic Compounds: Synthesis and Their Medicinal Activity Applications

Alheety,

Mohammed,

Farhan

et al. 2023

SynOpen

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Benzimidazole is a heterocyclic compound formed by fusing the benzene ring with an imidazole ring that contains two nitrogen atoms. Benzimidazole and its derivatives are prepared in different ways, including condensation of o-phenylenediamine with carbonyl compounds (aldehydes and ketones) or with carboxylic acids and their derivatives. The benzimidazoles can also be prepared by rearranging other heterocyclic compounds such as quinoxaline derivatives, triazole derivatives, etc. In recent decades, benzimidazoles were prepared using green methods such as microwaves, ultrasound, and the use of an environmentally friendly catalyst, as well as photochemical reactions. Benzimidazoles have attracted the interest of scientists and researchers due to the great medical efficacy shown by them for various diseases. The benzimidazole derivatives show many pharmacological activities such as anticancer, anti-inflammatory, antioxidant, anticoagulant, antiviral, etc. This review focuses on shedding light on benzimidazole and its derivatives, the most important methods used to prepare it, as well as the biological applications in our daily lives.

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Design, synthesis, kinetic, molecular dynamics, and hypoglycemic effect characterization of new and potential selective benzimidazole derivatives as Protein Tyrosine Phosphatase 1B inhibitors

Cited by 4 publications

References 77 publications

Development of Tyrosine Phosphatase 1B Inhibitors Based on Molecular Docking, Kinetics, and Toxicity Studies

Development of Tyrosine Phosphatase 1B Inhibitors Based on Molecular Docking, Kinetics, and Toxicity Studies

Recent updates on development of protein-tyrosine phosphatase 1B inhibitors for treatment of diabetes, obesity and related disorders

A Review on Benzimidazole Heterocyclic Compounds: Synthesis and Their Medicinal Activity Applications

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