Research Article

Synthesis and evaluation of novel peptidomimetics bearing p-aminobenzoic acid moiety as potential antidiabetic agents

Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry & Chemical Engineering, Institute of Bioorganic & Medicinal Chemistry, Southwest University, Chongqing, 400715, PR China

Key Laboratory of Freshwater Fish Reproduction & Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Chongqing, 400715, PR China

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Wen Hu

School of Chemistry & Chemical Engineering, Chongqing University, Chongqing, 400044, PR China

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Li Fan

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Hang Wang

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Min-Hui Tang

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Da-Cheng Yang

*Author for correspondence:

E-mail Address: hxydc@swu.edu.cn

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Published Online:25 Mar 2020https://doi.org/10.4155/fmc-2018-0372

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Abstract

Aim: Search for a new class of potential antidiabetic agents. Methodology: A series of novel peptidomimetics bearing the p-aminobenzoic acid moiety (TM3–TM6) were designed and synthesized. For all synthetic target molecules, the peroxisome proliferator response element (PPRE) activated activities have been evaluated and the toxicity were computed. Results & discussion: 46 new p-aminobenzoic acid derivatives have been characterized by ¹H NMR, ¹³C NMR and high-resolution mass spectrometry (HRMS). The results of in vitro PPRE-activated activity, molecular docking study and toxicity prediction revealed that these compounds had potential antidiabetic activities and low toxicity. In particular compound 3b had up to 87% PPRE-activated activity compared with pioglitazone. This discovery may provide new insights for finding novel PPRE lead compound.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 12, No. 11

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History

Received 2 August 2018

Accepted 4 March 2020

Published online 25 March 2020

Published in print June 2020

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Acknowledgments

The authors thank the Innovative Drug Center of Chengdu DiAo Pharmaceutical Group for assaying PPRE relative activity.

Financial & competing interests disclosure

This work was supported by the Natural Science Foundation Project of Chongqing (cstc2016jcyjA0421), the Fundamental Research Funds for the Central Universities(XDJK2019C043) and the National Natural Science Foundation of China (21542003). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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