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Toxicity Study of 3-Thienylalanine- Ornithine-Proline (TOP) Using as Novel ACE Inhibitor

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Abstract

Angiotensin converting enzyme inhibitor is a one of the best anti-hypertension well known drugs for treatment of hypertension (Cushman and Ondetti, Hypertension 17:589–592, 1991). In available ACE inhibitors have various side effects like angioedema, dry cough, skin irritation, and multiple dosing due to less bioavailability (Natesh et al., Nature 421:551–554, 2003, Natesh et al., Biochemistry 43:8718–8724, 2004). We had previously published the data for pharmacological profile and potency of a peptidomimetic compound, 3-Thienylalanine-Ornithine-Proline (TOP) is in-house compound. TOP has shown potent activity and a promising profile in in-vitro, ex-vivo and in-vivo assays as published previously from our laboratory (Seth et al., Drug Des Devel Ther, 2016, Chaudhary et al., J Cardiovasc Pharmacol 61:311–317, 2013). The potent and interesting pharmacological activity shown by this compound further forced us to look at the toxicological profile of this compound in in-vivo in sub-chronic dosing in different dose regime above its pharmacological dose. Therefore, in the current study, we aimed to evaluate the toxicity study that is the 28 days toxicity of our inhouse compound TOP applying the recommended OECD guidelines for safety. In this study, we have taken the dose 10 times higher dose than effective dose. However, our compound (TOP) did not show any toxic sign and symptom and no significantly adverse effect in blood chemistry, hematologic values and histology till higher dose 100 mg/kg. In conclusion, in this study TOP showed promising pharmacological activity without any signs of toxicity in animals.

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Acknowledgements

This study was supported by the Council of Scientific and Industrial Research, India.

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Authors and Affiliations

  1. Peptide Synthesis Laboratory, Institute of Genomics and Integrative Biology, CSIR, Delhi, India

    Mahesh Kumar Seth & Santosh Pasha

  2. Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, New Delhi, India

    Mahesh Kumar Seth & M. Ejaz Hussain

  3. Department of Physiology, VPCI, University of Delhi, Delhi, India

    Mahesh Kumar Seth & Mohammad Fahim

  4. Faculty of Allied Health Sciences, Shree Guru Gobind Singh Tricentenary ( SGT) University, Gurugram, Haryana, India

    Mahesh Kumar Seth & M. Ejaz Hussain

  5. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER) – Raebareli, Transit Campus, Bijnour-sisendi Road, Sarojini nagar, Lucknow, 226002, Uttar Pradesh, India

    Rakesh Kumar Singh

  6. Ranbaxy Research Laboratory, Gurgaon, Haryana, India

    Rakesh Kumar Singh

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Contributions

Mahesh Kumar Seth, I (Mahesh Kumar Seth) am corresponding author and all experiment performed by me with the help of co-authors i.e. Rakesh Kumar Singh, M Ejaz Hussain, Santosh Pasha, Mohammad Fahim and All co- authors reviewed the manuscript.

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Seth, M.K., Singh, R.K., Hussain, M. et al. Toxicity Study of 3-Thienylalanine- Ornithine-Proline (TOP) Using as Novel ACE Inhibitor. Int J Pept Res Ther 28, 150 (2022). https://doi.org/10.1007/s10989-022-10449-3

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