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Inhibition of Porcine Pancreatic Amylase Activity by Sulfamethoxazole: Structural and Functional Aspect

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Abstract

Combating Type-2 diabetes mellitus is a pivotal challenge in front of the present world. Several lines of therapy are in practice for resisting this deadly disease which often culminates with cardiovascular complexities, neuropathy and retinopathy. Among various therapies, administration of alpha glucosidase inhibitors is common and widely practiced. Sulfonylurea category of anti diabetic drug often suffers from cross reactivity with sulfamethoxazole (SMX), a common drug in use to treat a handful of microbial infections. However the specific cellular target generating postprandial hypoglycemia on SMX administration is till date unraveled. The present work has been initiated to elucidate the effects of a group of sulfonamide drugs inclusive of SMX for their amylase inhibitory role. SMX inhibits porcine pancreatic amylase (PPA) in a noncompetitive mode with an average IC50 value 0.94 mM respectively. Interaction of SMX with PPA is manifested with gradual quenching of tryptophan fluorescence with concomitant shift in lambda max value (λmax). Binding is governed by entropy driven factor (24.8 cal mol−1 K−1) with unfavorable contribution from enthalpy change. SMX interferes with the activity of acarbose in a synergistic mode to reduce the effective dose of acarbose as evident from the in vitro PPA inhibition study. In summary, loss of PPA activity in presence of SMX is indicative of structural changes of PPA which is further augmented in the presence of acarbose as explained in the schematic model and docking study.

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Abbreviations

PPA:

Porcine pancreatic amylase

SMX:

Sulfamethoxazole

ANS:

8-Anilino-1-naphthalenesulfonate

ITC:

Isothermal titration calorimetry

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Acknowledgement

The authors are thankful to the Department of Biotechnology, Haldia Institute of Technology for providing space and infrastructural support.

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Authors and Affiliations

  1. Department of Biotechnology, Haldia Institute of Technology, Haldia, Purba Medinipur, 721657, India

    Sujan Maity, Suman Mukherjee & Suvroma Gupta

  2. Department of Bio-Engineering, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835215, India

    Koel Mukherjee

  3. Molecular Biophysics Unit, Saha Institute of Nuclear Physics, Kolkata, West Bengal, India

    Amrita Banerjee & Dipak Dasgupta

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  1. Sujan Maity
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Correspondence to Suvroma Gupta.

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Maity, S., Mukherjee, K., Banerjee, A. et al. Inhibition of Porcine Pancreatic Amylase Activity by Sulfamethoxazole: Structural and Functional Aspect. Protein J 35, 237–246 (2016). https://doi.org/10.1007/s10930-016-9668-8

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