1. Academic Validation
  2. Design, Synthesis, and the Effects of ( E)-9-Oxooctadec-10-en-12-ynoic Acid Analogues to Promote Glucose Uptake

Design, Synthesis, and the Effects of ( E)-9-Oxooctadec-10-en-12-ynoic Acid Analogues to Promote Glucose Uptake

  • ACS Omega. 2021 Sep 9;6(37):24118-24127. doi: 10.1021/acsomega.1c03600.
Rajendra R Kshirsagar 1 2 Pradip K Gadekar 3 Vijay M Khedkar 4 Vijayaparthasarathi Vijayakumar 1
Affiliations

Affiliations

  • 1 Centre for Organic and Medicinal Chemistry, Department of Chemistry, School of Advanced Sciences, VIT University, Vellore, Tamil Nadu 632014, India.
  • 2 Discovery Analytical Sciences Department, Piramal Enterprises Limited, 1A - Nirlon Complex, Off Western Express Highway, Goregaon (East), Mumbai, Maharashtra 400 063, India.
  • 3 Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
  • 4 Department of Pharmaceutical Chemistry, School of Pharmacy, Vishwakarma University, Pune, Maharashtra 411 048, India.
Abstract

(E)-9-Oxooctadec-10-en-12-ynoic acid is found to mediate its antidiabetic activity by increasing insulin-stimulated glucose uptake in L6 myotubes by activating the phosphoinositide 3-kinase (PI3K) pathway. A simultaneous study of site-specific modification followed by structure-activity relationship provides a tremendous scope for exploiting the bioactivity of the parent molecule. Therefore, in the present study, we focused on site-specific modification of (E)-9-oxooctadec-10-en-12-ynoic acid (1) to generate multiple derivatives and extensive structure-activity relationship (SAR) studies. We have done structural base design and synthesized a series of amides from acid compound 1. Compound 1 consists of an acid functionality, which is known for its metabolism-related liabilities. The SAR has been generated using scaffolds of different antidiabetic drugs such as biguanides, sulfonylureas, thiazolidinediones/glitazones, peroxisome proliferator-activated receptors, K + ATP, α-glucosidase inhibitors, and Others. Furthermore, the study demonstrates and explains the promising derivatives and importance of SAR of the compound (E)-9-oxooctadec-10-en-12-ynoic acid. In order to gain mechanistic insights, a molecular docking study was performed against PI3K, which could identify the binding modes and thermodynamic interactions governing the binding affinity. According to our research, compounds 5, 6, 27, 28, 31, 32, and 33 are the best compounds from the series having EC50 values of 15.47, 8.89, 7.00, 13.99, 8.70, 12.27, and 16.14 μM, respectively.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-132898
    PI3K Activator