Development of sulfonamide-based Schiff bases targeting urease inhibition: Synthesis, characterization, inhibitory activity assessment, molecular docking and ADME studies

Hamad, Asad; Khan, Mohsin Abbas; Rahman, Khondaker Miraz; Ahmad, Irshad; Ul-Haq, Zaheer; Khan, Samra; Shafiq, Zahid

doi:10.1016/j.bioorg.2020.104057

Cited by 44 publications

(19 citation statements)

References 40 publications

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“…Their activity as antimicrobial, anti-inflammatory, anticancer and antioxidants is well recognized. [28][29][30][31][32][33][34] Moreover, iodine has been reported to have a higher antioxidant potential than ascorbic acid. 35 Iodine is an electron donor that can quench ROS as OH • and H 2 O 2 , 36 thus increasing the total antioxidant status in the body.…”

mentioning

confidence: 99%

Novel iodinated quinazolinones bearing sulfonamide as new scaffold targeting radiation induced oxidative stress

Soliman

Mekkawy

Karam

et al. 2021

Bioorganic & Medicinal Chemistry Letters

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confidence: 99%

Novel iodinated quinazolinones bearing sulfonamide as new scaffold targeting radiation induced oxidative stress

Soliman

Mekkawy

Karam

et al. 2021

Bioorganic & Medicinal Chemistry Letters

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“…The structures of the synthesized Schiff bases were fully characterized with the help of 1 H NMR, 13 C NMR, and HRMS (ESI). Schiff bases of this type were previously reported by us (Hamad, Abbas Khan, et al, 2020 ; Hamad, Khan, et al, 2020 ), and the NMR data were compared with the literature, where applicable.…”

Section: Resultsmentioning

confidence: 99%

Schiff bases of sulphonamides as a new class of antifungal agent against multidrug‐resistant Candida auris

et al. 2021

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Invasive Candida infections in hospitalized and immunocompromised or critically ill patients have become an important cause of morbidity and mortality. There are increasing reports of multidrug resistance in several Candida species that cause Candidemia, including C . glabrata and C. auris , with limited numbers of antifungal agents available to treat patients with invasive Candida infections. Therefore, there is an urgent need to discover new antifungal agents that work against multidrug‐resistant Candida species, particularly C . auris , which has been identified as an emerging global pathogen. In this article, we report a new class of antifungal agents, the Schiff bases of sulphonamides, that show activity against all Candida species tested, with an MIC range of 4–32 µg/ml. Compound 2b showed activity against C . glabrata and a panel of fluconazole‐resistant C . auris strains, with MICs of 4–16 µg/ml. The drug‐like nature of these Schiff bases offers opportunities to optimize these compounds with medicinal chemistry techniques to obtain more potent analogs that can be progressed toward pre‐clinical evaluation.

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“…The urease enzyme’s hyperactivity releases an excessive amount of ammonia causing alkalinity in the stomach, consequently, enhancing the permeability of the gastric mucosa. − Although humans lack the urease enzymes, urea is synthesized as the end product of protein metabolism in them that is usually eliminated from the body in the form of urine. − Action of urease enzymes in cattle and many other animals also facilitates monitoring and regulating their nitrogen metabolism. , Different pathogenic conditions can arise due to the elevated levels of these enzymes, especially, they assist in the flourishing of various bacterial infections, leading to some grave adverse effects . The growth of Helicobacter pylori (HP) is eased via the assistance of low pH of the stomach in humans, eventually causing the peptic and gastric ulcers, finally leading to cancer. − Moreover, various metabolic dysregulations can arise due to the elevated level of ammonia abolishing the gastrointestinal tract (GIT) epithelium. , Furthermore, kidney stone formation is also instigated via a high urease level…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of 1,3,5-Triaryl-2-Pyrazoline Derivatives as Potent Dual Inhibitors of Urease and α-Glucosidase Together with Their Cytotoxic, Molecular Modeling and Drug-Likeness Studies

Mehmood¹,

Sadiq²,

Alsantali

et al. 2022

ACS Omega

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In the present work, a concise library of 1,3,5triaryl-2-pyrazolines (2a−2q) was designed and synthesized by employing a multistep strategy, and the newly synthesized compounds were screened for their urease and α-glucosidase inhibitory activities. The compounds (2a−2q) were characterized using a combination of several spectroscopic techniques including FT-IR, 1 H NMR, 13 C NMR, and EI-MS. All the synthesized compounds, except compound 2i, were potent against urease as compared to the standard inhibitor thiourea (IC 50 = 21.37 ± 0.26 μM). These analogs disclosed varying degrees of urease inhibitory activities ranging from 9.13 ± 0.25 to 18.42 ± 0.42 μM. Compounds 2b, 2g, 2m, and 2q having IC 50 values of 9.36 ± 0.27, 9.13 ± 0.25, 9.18 ± 0.35, and 9.35 ± 0.35 μM, respectively, showed excellent inhibitory activity as compared to standard thiourea (IC 50 = 21.37 ± 0.26 μM). A kinetic study of compound 2g revealed that compound 2g inhibited urease in a competitive mode. Among the synthesized pyrazolines, the compounds 2c, 2k, 2m, and 2o exhibited excellent α-glucosidase inhibitory activity with the lowest IC 50 values of 212.52 ± 1.31, 237.26 ± 1.28, 138.35 ± 1.32, and 114.57 ± 1.35 μM, respectively, as compared to the standard acarbose (IC 50 = 375.82 ± 1.76 μM). The compounds (2a− 2q) showed α-glucosidase IC 50 values in the range of 114.57 ± 1.35 to 462.94 ± 1.23 μM. Structure−activity relationship revealed that the size and electron-donating or -withdrawing effects of substituents influenced the activities, which led to the urease and αglucosidase inhibiting properties. Compound 2m was a dual potent inhibitor against urease and α-glucosidase due to the presence of 2-CF 3 electron-withdrawing functionality on the phenyl ring. To the best of our knowledge, these synthetic compounds were found to be the most potent dual inhibitors of urease and α-glucosidase with minimum IC 50 values. The cytotoxicity of the compounds (2a−2q) was also investigated against human cell lines MCF-7 and HeLa. Compound 2l showed moderate cytotoxic activity against MCF-7 and HeLa cell lines. Moreover, in silico studies on most active compounds were also performed to understand the binding interaction of most active compounds with active sites of urease and α-glucosidase enzymes. Some compounds exhibited drug-like characteristics due to their lower cytotoxic and good ADME profiles.

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Development of sulfonamide-based Schiff bases targeting urease inhibition: Synthesis, characterization, inhibitory activity assessment, molecular docking and ADME studies

Cited by 44 publications

References 40 publications

Novel iodinated quinazolinones bearing sulfonamide as new scaffold targeting radiation induced oxidative stress

Novel iodinated quinazolinones bearing sulfonamide as new scaffold targeting radiation induced oxidative stress

Schiff bases of sulphonamides as a new class of antifungal agent against multidrug‐resistant Candida auris

Synthesis and Evaluation of 1,3,5-Triaryl-2-Pyrazoline Derivatives as Potent Dual Inhibitors of Urease and α-Glucosidase Together with Their Cytotoxic, Molecular Modeling and Drug-Likeness Studies

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