Bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis

Abstract Current research is based on biology-oriented synthesis of sulphadiazine derivatives and determination of their urease inhibitory activity. In this regard, a series of (E)-4-(benzylideneamino)-N-(pyrimidin-2-yl)benzenesulfonamide was synthesized from sulphadiazine and substituted aromatic a...

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Autores principales:	Asad Hamad, Mohsin Abbas Khan, Irshad Ahmad, Ruqaiya Khalil, Muhammad Khalid, Urva Abbas, Rahat Azhar, Jalal Uddin, Gaber El-Saber Batiha, Ajmal Khan, Zahid Shafiq, Ahmed Al-Harrasi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b3f54ea4bfa3458e9557fb8910cb5571
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spelling	oai:doaj.org-article:b3f54ea4bfa3458e9557fb8910cb55712021-12-02T18:48:02ZBio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis10.1038/s41598-021-98413-x2045-2322https://doaj.org/article/b3f54ea4bfa3458e9557fb8910cb55712021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98413-xhttps://doaj.org/toc/2045-2322Abstract Current research is based on biology-oriented synthesis of sulphadiazine derivatives and determination of their urease inhibitory activity. In this regard, a series of (E)-4-(benzylideneamino)-N-(pyrimidin-2-yl)benzenesulfonamide was synthesized from sulphadiazine and substituted aromatic aldehydes. The structures of synthesized compounds were ascertained by spectroscopic techniques, such as, FTIR, NMR and HRMS analysis, and in-vitro and in-silico investigation were carried out for the inhibition of urease. Ureases are harmful for humans by producing by-products of urea (ammonia and carbon dioxide). The most active compound (3l) against urease exhibited IC50 value of 2.21 ± 0.45 µM which is 10 times more potent than the standard thiourea (20.03 ± 2.06 µM). It is noteworthy that most of our synthesized compounds showed significant to excellent activities against urease enzyme and most of them substituted by halogen or hydroxy groups at ortho and para positions in their structures. Inhibition of enzyme by the synthesized analogues was in descending order as 3l > 3a > 3b > 3q > 3e > 3o > 3s > 3t > 3g > 3k > 3r > 3f > 3m > 3p > 3n > 3j > 3i > 3h. Moreover, molecular docking studies were performed to rationalize the binding interactions of the synthesized motifs with the active pocket of the urease enzyme. The synthesized sulphadiazine derivatives (3a–u) were found to be non-toxic, and presented passive gastrointestinal absorption.Asad HamadMohsin Abbas KhanIrshad AhmadRuqaiya KhalilMuhammad KhalidUrva AbbasRahat AzharJalal UddinGaber El-Saber BatihaAjmal KhanZahid ShafiqAhmed Al-HarrasiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Asad Hamad Mohsin Abbas Khan Irshad Ahmad Ruqaiya Khalil Muhammad Khalid Urva Abbas Rahat Azhar Jalal Uddin Gaber El-Saber Batiha Ajmal Khan Zahid Shafiq Ahmed Al-Harrasi Bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis
description	Abstract Current research is based on biology-oriented synthesis of sulphadiazine derivatives and determination of their urease inhibitory activity. In this regard, a series of (E)-4-(benzylideneamino)-N-(pyrimidin-2-yl)benzenesulfonamide was synthesized from sulphadiazine and substituted aromatic aldehydes. The structures of synthesized compounds were ascertained by spectroscopic techniques, such as, FTIR, NMR and HRMS analysis, and in-vitro and in-silico investigation were carried out for the inhibition of urease. Ureases are harmful for humans by producing by-products of urea (ammonia and carbon dioxide). The most active compound (3l) against urease exhibited IC50 value of 2.21 ± 0.45 µM which is 10 times more potent than the standard thiourea (20.03 ± 2.06 µM). It is noteworthy that most of our synthesized compounds showed significant to excellent activities against urease enzyme and most of them substituted by halogen or hydroxy groups at ortho and para positions in their structures. Inhibition of enzyme by the synthesized analogues was in descending order as 3l > 3a > 3b > 3q > 3e > 3o > 3s > 3t > 3g > 3k > 3r > 3f > 3m > 3p > 3n > 3j > 3i > 3h. Moreover, molecular docking studies were performed to rationalize the binding interactions of the synthesized motifs with the active pocket of the urease enzyme. The synthesized sulphadiazine derivatives (3a–u) were found to be non-toxic, and presented passive gastrointestinal absorption.
format	article
author	Asad Hamad Mohsin Abbas Khan Irshad Ahmad Ruqaiya Khalil Muhammad Khalid Urva Abbas Rahat Azhar Jalal Uddin Gaber El-Saber Batiha Ajmal Khan Zahid Shafiq Ahmed Al-Harrasi
author_facet	Asad Hamad Mohsin Abbas Khan Irshad Ahmad Ruqaiya Khalil Muhammad Khalid Urva Abbas Rahat Azhar Jalal Uddin Gaber El-Saber Batiha Ajmal Khan Zahid Shafiq Ahmed Al-Harrasi
author_sort	Asad Hamad
title	Bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis
title_short	Bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis
title_full	Bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis
title_fullStr	Bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis
title_full_unstemmed	Bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis
title_sort	bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b3f54ea4bfa3458e9557fb8910cb5571
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Bio-oriented synthesis of new sulphadiazine derivatives for urease inhibition and their pharmacokinetic analysis

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