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Identification and evaluation of natural organosulfur compounds as potential dual inhibitors of α-amylase and α-glucosidase activity: an in-silico and in-vitro approach

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Abstract

We aimed to identify and evaluate natural organosulfur compounds (OSCs) from the genus Allium as potent dual inhibitors of α-amylase and α-glucosidase via a set of molecular simulations and in-vitro analysis. We reported that all OSCs fall under the acceptable scores of Lipinski’s rules and desirable ADME parameters. In-silico screening revealed that OSCs strongly interacted with α-amylase and α-glucosidase crystal structures. Our in-vitro studies with four OSCs having best ΔG-scores demonstrated that alliin, S-allyl-L-cysteine (SAC), N-acetylcysteine (NAC), and S-ethyl-L-cysteine (SEC) exhibit a marked in-vitro inhibition of α-amylase activity, whereas, γ-glutamylcysteine (GGC), SEC, alliin, and SAC potentially inhibited the in-vitro α-glucosidase activity. Our enzyme kinetics studies depicted that the selected OSCs competitively inhibited the α-amylase and α-glucosidase activity. In conclusion, this initial in-silico and the in-vitro report demonstrates the drug-likeness and ADME indices of OSCs and identifies alliin, SAC, NAC, SEC, and GGC as potential dual inhibitors of α-amylase and α-glucosidase.

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Acknowledgements

The authors are highly indebted to the Department of Health Research (DHR), Ministry of Health & Family Welfare (MoHFW), Govt. of India, for providing the Young Scientist Grant (YSS Project No. 12014/13/2019-HR) for the smooth conduction of this work. The authors are also thankful to Integral University for providing laboratory for the smooth completion of this work. This paper has Integral University manuscript communication no. IU/R&D/2021-MCN0001155.

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  1. These authors contributed equally: Parvej Ahmad, Sahir Sultan Alvi

Authors and Affiliations

  1. IIRC-5, Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral University, Lucknow, U.P., 226026, India

    Parvej Ahmad, Sahir Sultan Alvi & M. Salman Khan

  2. Department of Biochemistry, Faculty of Medicine, Jazan University, Jazan, Kingdom of Saudi Arabia

    Johar Iqbal

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Author contributionsInterventional hypothesis: MSK; In-silico and biochemical measurements: PA & SSA; Data analysis: SSA & PA; Paper writing and Figure preparation: PA, & SSA; Statistical analysis: PA & SSA; Revision, English editing & approval of the final paper: JI, MSK & SSA.

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Ahmad, P., Alvi, S.S., Iqbal, J. et al. Identification and evaluation of natural organosulfur compounds as potential dual inhibitors of α-amylase and α-glucosidase activity: an in-silico and in-vitro approach. Med Chem Res 30, 2184–2202 (2021). https://doi.org/10.1007/s00044-021-02799-2

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