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. 2019 May 1;9(1):6738.
doi: 10.1038/s41598-019-43082-0.

Studies on Isoniazid Derivatives through a Medicinal Chemistry Approach for the Identification of New Inhibitors of Urease and Inflammatory Markers

Fazila Rizvi  1 , Majid Khan  1 , Almas Jabeen  2 , Hina Siddiqui  3 , M Iqbal Choudhary  4   5   6
Affiliations

Studies on Isoniazid Derivatives through a Medicinal Chemistry Approach for the Identification of New Inhibitors of Urease and Inflammatory Markers

Fazila Rizvi et al. Sci Rep. .

Abstract

A library of thiosemicarbazide derivatives of isoniazid 3-27, was synthesized and evaluated for their anti-inflammatory and urease inhibition activities, by using in vitro bioassays. Among these compounds 9, 10, 12, 21, and 26 were identified as new derivatives. Prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) and infections caused by Helicobacter pylori (ureolytic bacteria), are the two most significant causes of gastric and peptic ulcers. We focused on the identification of the dual inhibitors of inflammation and urease enzyme. Compound 23 was identified as the best dual inhibitor of inflammation (ROS; IC50 = 12.3 µg/mL), and urease enzyme inhibition activity (IC50 = 22.4 µM). Many of these compounds showed comparable activities to the standard anti-inflammatory drug (ibuprofen, IC50 = 11.2 µg/mL) and urease inhibitor (thiourea/acetohydraoxamic acid, IC50 = 21.1/20.3 µM). Compound 12 was found to be the most potent urease inhibitor (IC50 = 12.3 µM) and good inhibitor of inflammation (IC50 = 27.7 µg/mL). Compounds 19, 11, 13, 9, 17, 10, and 16, were also found to be potent inhibitors of urease. Cytotoxicity was also evaluated and all the compounds were found to be non-cytotoxic, except compound 18 and the parent drug isoniazid (IC50 = 29.5 and 28.5 µM, respectively).

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Examples of Non-Steroidal Anti-inflammatory Drugs.
Figure 2
Figure 2
Examples of Urease Inhibitors Used as Anti-Ulcer Drugs.
Figure 3
Figure 3
Some previously reported derivatives of isoniazid.
Figure 4
Figure 4
Component structural similarities between isoniazid, etoricoxib, and pantoprazole.
Figure 5
Figure 5
Isoniazid (1).
Figure 6
Figure 6
Synthesis of thiosemicarbazide derivatives of isoniazid (3–27).
Figure 7
Figure 7
NMR and Key 2D NOSEY correlations of N-(2, 3-Dichlorophenyl)−2-isonicotinoylhydrazinecarbothioamide (4).
Figure 8
Figure 8
Rationale of the biological activity.
See this image and copyright information in PMC

References

    1. Hanif, M. et al. Synthesis, urease inhibition, anti-oxidant, anti-bacterial, and molecular docking studies of 1,3,4-oxadiazole derivatives. Int. Sch. Res. Notices (2012). - PMC - PubMed
    1. Perveen S, Khan KM, Lodhi MA, Choudhary MI, Voelter W. Urease and α-chymotrypsin inhibitory effects of selected urea derivatives. Lett. Drug Des. Discov. 2008;5:401–405. doi: 10.2174/157018008785777315. - DOI
    1. Sadat A, Uddin G, Alam M, Ahmad A, Siddiqui BS. Structure -activity relationship of bergenin, p-hydroxybenzoyl bergenin, 11-O-galloylbergenin as potent anti-oxidant and urease inhibitor isolated from bergenia ligulata. Nat. Prod. Res. 2015;29:2291–2294. doi: 10.1080/14786419.2015.1004173. - DOI - PubMed
    1. Krishnaraju AV, Rao CB, Sundararaju D, Sengupta K, Trimurtulu G. Anti-inflammatory activity of Vitex leucoxylonl. bark extracts against fremiti’s complete adjuvant induced arthritis in Sprague Daw ley Rat. Am. J. Infect. Dis. 2009;5:68–73. doi: 10.3844/ajidsp.2009.68.73. - DOI
    1. Leelaprakash G, Dass SM. Invitro anti-inflammatory activity of methanol extract of Enicostemma axillare. Int. J. Drug Dev. Res. 2011;3:189–196.

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