2. Academic Validation
  3. Discovery of new pyridine 3-carboxylic acid-based pharmacophores as dual anti-inflammatory and anti-hyperglycemic agents

Discovery of new pyridine 3-carboxylic acid-based pharmacophores as dual anti-inflammatory and anti-hyperglycemic agents

  • Sci Rep. 2025 Oct 3;15(1):34536. doi: 10.1038/s41598-025-17841-1.
K Ramakrishnan 1,  Lenin Nachimuthu 1,  Reshma Rajan 1,  J Premkumar 1,  Vallabh Mulay 1,  S Meenakshi 2,  Chandrakala A Narasimhulu 3,  Pragney Deme 4,  Sanjay Rajagopalan 5,  Ramanathan Lalgudi 6,  Akella Sivaramakrishna 1,  S Karthikeyan 1,  Rajagopal Desikan 7
Affiliations

Affiliations

  • 1 Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore, 632014, Tamilnadu, India.
  • 2 Department of English, School of Social Sciences and Languages, Vellore Institute of Technology, Vellore, 632014, Tamilnadu, India.
  • 3 Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, University Of Central Florida, Orlando, USA.
  • 4 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 5 Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
  • 6 Aries Science & Technology, Columbus, OH, USA.
  • 7 Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore, 632014, Tamilnadu, India. rajagopal.desikan@vit.ac.in.
PMID: 41044118 DOI: 10.1038/s41598-025-17841-1
Abstract

Novel nicotinic acid derivatives were synthesized as potent anti-diabetic agents. The developed inhibitors were investigated for their pharmacological in vitro screening, such as anti-diabetic, anti-inflammation, and in silico analysis. It has good interactions with α-amylase protein, with a range of -7.18 to -5.55 kcal/mol. The inhibitors were synthesized by employing the Steglich-type reaction to couple alcohol and amine derivatives. These molecules were characterized using NMR, FT-IR, and Mass spectrometry techniques. Anti-hyperglycemic activity has been screened using α-amylase protein, and the half-maximal inhibition efficiency (IC50) value was evaluated, ranging from 1.324 ± 0.17 to 1.516 ± 0.14 µg. The positive control (acarbose) range is 1.273 ± 0.12 µg. Induced human RBC hemolysis assay was utilized for anti-inflammatory activity, and the cumulative observation results were compared with the reference drug (ketorolac- IC50 = 11.79 ± 0.17 µM), with IC50 values between 14.06 ± 0.15 to 85.56 ± 0.25 µM. Moreover, the antioxidant ability of synthesized inhibitor compounds was evaluated by radical scavenging methods. The efficacy of inhibitors 2b and 2 h (IC50 = 15.63 ± 0.13 µM and 12.88 ± 0.19 µM (DPPH), IC50 = 19.89 ± 0.25 µM and 16.35 ± 0.25 µM (ABTS)) exhibited good results against DPPH and ABTS radicals with ascorbic acid(standard) (DPPH: IC50 = 11.81 ± 0.04 µM and ABTS: 11.90 ± 0.01 µM). The synthesized derivatives show promising results of anti-inflammatory and anti-hyperglycemic properties. This provides a path to developing the new therapeutic agents for inflammation.

Keywords

Anti-hyperglycemic activity; Anti-inflammatory; Anti-oxidant; Nicotinic acid; Α-amylase.

Figures
Products