Hydrochlorothiazide and Indapamide bind the NADPH binding site of bacterial Dihydrofolate Reductase: results of an in-si
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ORIGINAL RESEARCH
Hydrochlorothiazide and Indapamide bind the NADPH binding site of bacterial Dihydrofolate Reductase: results of an in‑silico study and their implications Sumanpreet Kaur1 · Rajasri Bhattacharyya1 · Dibyajyoti Banerjee1 Received: 30 June 2020 / Accepted: 28 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Hypertension · Diuretics · Thiazide · Sulphonamide · Antibiotics · Gut microbiome · Diabetes mellitus
Introduction Hypertension is a silent killer of humans (Arima et al. 2011). It precipitates coronary artery disease, cerebrovascular accident, and chronic renal failure, to name a few (Escobar 2002). Decades of research have led to the development of several classes of antihypertensive medications with different targets, which are used alone or in combination. Among the antihypertensive drugs, Sulphonamide Diuretics are a class of their own. These are commonly used medications for treating hypertension and offer an extra benefit to patients in low doses. They are more effective than other Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40203-020-00056-9) contains supplementary material, which is available to authorized users. * Rajasri Bhattacharyya [email protected] * Dibyajyoti Banerjee [email protected] 1
Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
classes of antihypertensive agents (Roush and Sica 2016). Hydrochlorothiazide is perhaps one of the most commonly used Diuretic. It is often used orally as a first-line antihypertensive medication (Roush and Sica 2016). Indapamide is also a thiazide-like Diuretic. Some authorities believe that Indapamide controls systolic blood pressure better than Hydrochlorothiazide (Roush and Sica 2016). Several Sulphonamides are known to have antimicrobial activity by binding to bacterial Dihydrofolate Reductase (DHFR) enzyme (Reeves et al. 1978; Wood 1942). DHFR is a critical e
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