Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

ABSTRACT

The zinc-dependent enzyme aminopeptidase N (APN) is a member of the M1 metalloenzyme family. The multi-functionality of APN as a peptidase, a receptor and a signalling molecule has provided it the access to influence a number of disease conditions namely viral diseases, angiogenesis, cellular metastasis and invasion including different cancer conditions. Hence, the development of potent APN inhibitors is a possible route for the treatment of diseases related to the activity of APN. In this study, different QSAR approaches have been adopted to identify the structural features of a group of hydroxamate-based ureido-amino acid derivative APN inhibitors. This study was able to identify different constitutional aspects of these APN inhibitors which are important for their inhibitory potency. Additionally, some of these observations were also aligned with the observations of previously performed QSAR studies conducted on different APN inhibitors. Therefore, the results of this study may help to design potent and effective APN inhibitors in the future.

KEYWORDS:

• Aminopeptidase-N
• APN inhibitor
• 2D-QSAR
• LDA
• Bayesian classification model

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Acknowledgements

Suvankar Banerjee is grateful to the RUSA 2.0 of University Grant Commission (UGC), New Delhi, India to Jadavpur University, Kolkata, India for awarding fellowship [REF. NO: R-11/1030/19, Dated: 30-07-2019]. Sk. Abdul Amin is thankful to Council of Scientific and Industrial Research (CSIR), New Delhi, India for awarding the Senior Research Fellowship [FILE NO: 09/096(0967)/2019-EMR-I, Dated: 01-04-2019]. Sandip Kumar Baidya sincerely acknowledges Indian Council for Medical Research (ICMR) for awarding a fellowship. Nilanjan Adhikari is grateful to CSIR, New Delhi, India for providing research associateship (RA) [FILE NO: 09/096(0966)/2019-EMR-I, Dated: 28-03-2019]. Tarun Jha is also thankful for the financial support from RUSA 2.0 of UGC, New Delhi, India to Jadavpur University, Kolkata, India. We also thank the support from the Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India for providing the research facilities. The authors are also thankful to Mr Saptarshi Sanyal for his support.

Disclosure statement

The authors have no conflict of interests.

Supplementary material

Supplementary data for this article can be accessed at: https://doi.org/10.1080/1062936X.2020.1734080.

Additional information

Funding

This work was supported by the Council of Scientific and Industrial Research (CSIR), New Delhi [FILE NO: 09/096(0967)/2019-EMR-I, Dated: 01-04-2019];RUSA 2.0 of University Grant Commission (UGC), New Delhi [REF. NO: R-11/1030/19, Dated: 30-07-2019].