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Journal of Pharmaceutical Research

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Synthesis and Evaluation of Nitric Oxide Donating Indolizinyl Pyrazoline Derivatives for Antihypertensive Activity
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Journal of Pharmaceutical Research

DOI: 10.18579/jopcr/v19.3.ronak

Year: 2020, Volume: 19, Issue: 3, Pages: 12-19

Original Article

Synthesis and Evaluation of Nitric Oxide Donating Indolizinyl Pyrazoline Derivatives for Antihypertensive Activity

A Lunagariya Ronak1, G Manjunath1,∗

1Department of Pharmaceutical Chemistry, Krupanidhi College of Pharmacy, Bangalore, Karnataka, India

 

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Hypertension, a leading cause of cardiovascular morbidity, necessitates novel therapeutic strategies that target vasodilation and endothelial dysfunction. In this study, four nitric oxide (NO)-donating indolizinyl pyrazoline derivatives (CNPH-1, CNPN-2, CRPH-3, and CRPN-4) were synthesised through a multi-step reaction scheme, integrating indolizine and pyrazoline rings with NO-releasing side chains. The compounds were characterised using melting point, thin-layer chromatography, infrared spectroscopy, and nuclear magnetic resonance spectroscopy to confirm their structural integrity. Pharmacological efficacy was evaluated by experimentally inducing hypertension in rats (Goldblatt method followed by the tail cuff method) and comparing systolic blood pressure (BP) reduction with nifedipine and clonidine. All derivatives significantly lowered BP within 120 min (p < 0.001 vs. controls), with CRPN-4 exhibiting sustained effects comparable to those of standard drugs at 240 min (25–30% reduction). At 360 min, the efficacy diminished, mirroring the transient action of nifedipine and clonidine. CRPN-4, which is characterised by moderate molecular weight and stability, has emerged as a lead candidate, likely because of the optimal NO release kinetics from its alkyl side chains. These findings underscore the potential of NO-donating pyrazoline hybrids for hypertension management by combining vasodilatory mechanisms with endothelial repair. Future studies should explore the pharmacokinetics, long-term efficacy, and toxicity of to advance CRPN-4 its clinical development. This study highlights the therapeutic potential of structurally engineered NO donors to address hypertension.

Keywords: Hypertension, Endothelial dysfunction, Nitric oxide, Indolizinyl pyrazoline

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Copyright

© 2020 Published by Krupanidhi College of Pharmacy. This is an open-access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/) 

  • 10 July 2025

Year: 2020, Volume: 19, Issue: 3


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