Hydrochlorothiazide and Indapamide bind the NADPH binding site of bacterial Dihydrofolate Reductase: results of an in-silico study and their implications

Abstract

Hypertension is a public health concern. Low dose thiazide diuretics are known to effectively control blood pressure compared to that of other classes of antihypertensive drugs. In this context, we have performed an in-silico study and found that the two Sulphonamide Diuretics Hydrochlorothiazide and Indapamide bound the NADPH binding region of bacterial Dihydrofolate Reductase. Therefore, akin to Sulphonamide Antibiotics, Sulphonamide Diuretics may have antibiotic activity and thereby have the potential to modulate the gut microbiome in a way beneficial to vascular health. The in-silico experiment results were analyzed in the context of the relevant literature. We postulate that Sulphonamide Diuretics exert their antihypertensive role by modulating the gut microbiome, specifically by increasing butyrate-producing taxa in the gut. We recommend extending such work as it is plausible that Indapamide and other Sulphonamide Diuretics may be beneficial for both diabetes and hypertension.

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Acknowledgements

SK and DB acknowledge PGIMER, Chandigarh for providing financial assistance vide Endst No. PGI/MERC/2020/4655-58 dated 7.10.2019 (Collectively) and No. 71/2-Edu-16/415 dated 23.1.2019.

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Correspondence to Rajasri Bhattacharyya or Dibyajyoti Banerjee.

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Kaur, S., Bhattacharyya, R. & Banerjee, D. Hydrochlorothiazide and Indapamide bind the NADPH binding site of bacterial Dihydrofolate Reductase: results of an in-silico study and their implications. In Silico Pharmacol. 8, 5 (2020). https://doi.org/10.1007/s40203-020-00056-9

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Keywords

  • Hypertension
  • Diuretics
  • Thiazide
  • Sulphonamide
  • Antibiotics
  • Gut microbiome
  • Diabetes mellitus