Synthesis, biological evaluation and molecular docking of N-phenyl thiosemicarbazones as urease inhibitors

Hameed, Abdul; Khan, Khalid Mohammed; Zehra, Syeda Tazeen; Ahmed, Ramasa; Shafiq, Zahid; Bakht, Syeda Mahwish; Yaqub, Muhammad; Hussain, Mazhar; Léon, Antonio de la Vega de; Furtmann, Norbert; Bajorath, Jürgen; Shad, Hazoor Ahmad; Tahir, Muhammad Nawaz; Iqbal, Jamshed

doi:10.1016/j.bioorg.2015.06.004

Cited by 65 publications

(22 citation statements)

References 36 publications

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“…Moreover, a same benzene oxygen moiety at ortho ‐position interacts with Ala636 and forms hydrogen bond having distance 2.55 Å. Gly550 also take part in hydrogen bonding with oxygen of same the benzene ring with a distance 2.59 Å. Literature study also showed that these interacted residues are significant for downstream signaling pathways and support our docking results . Our docking results may be good agreement with in vitro and in vivo analysis.…”

Section: Resultssupporting

confidence: 88%

In Vitro, In Silico Elucidation of Antiurease Activity, Kinetic Mechanism and COX‐2 Inhibitory Efficacy of Coagulansin A of Withania coagulans

Phull

Hassan

Abbas

et al. 2018

Chemistry & Biodiversity

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Urease enzyme plays a crucial role in the survival of Helicobacter pylori that contributes to different diseases, including peptic ulcer (gastric and duodenal ulcers). Coagulansin A is the steroidal lactone (withanolide) found in plants of solanaceae family such Withania coagulans. The current study was carried out to examine the in vitro urease, COX-2 inhibitory activity and effect on type II collagen expression of coagulansin A. Moreover, we investigated cytotoxic effects on rabbit articular chondrocytes through MTT assay. COX-2 and type II collagen expressions were determined through a Western blot method. Molecular docking and simulation studies of urease (PDBID 4H9M) and COX-2 (PDBID 5F1A) proteins were also performed as an in silico approach. Results showed that COX-2 expression was decreased dose dependably, significantly higher expression of type II collagen was observed at higher doses. In the current study, coagulansin A was found as non-toxic, and showed notable urease inhibitory activity in non-competitive manner with IC 23.14 μm in comparison to reference drug thiourea 17.81 μm. Significant decrease in COX-2 expression (40%) and increase in type II collagen (20%) were observed as compared to control. In silico results unveiled the strong binding affinities of coagulansin A with both of these urease and COX-2 proteins. Therefore, herein we proposed the significant antiurease potential of this compound that could be used in treating different diseases such as ulcers. Moreover, detailed in vivo studies and molecular mechanism based studies are suggested.

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Section: Resultssupporting

confidence: 88%

In Vitro, In Silico Elucidation of Antiurease Activity, Kinetic Mechanism and COX‐2 Inhibitory Efficacy of Coagulansin A of Withania coagulans

Phull

Hassan

Abbas

et al. 2018

Chemistry & Biodiversity

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“…Similarly, carbonyl methoxy and sulfur functional groups form hydrogen bonds against Asp494 having bonding distance 2.95 Å and 2.09 Å, respectively. Literature study also justified the significance of these interacted residues in hydrogen bonding which strengthen our docking results . The detail binding pattern of all the complexes is mentioned in supplementary data (Table.…”

Section: Resultssupporting

confidence: 82%

Synthesis, enzyme inhibitory kinetics, and computational studies of novel 1‐(2‐(4‐isobutylphenyl) propanoyl)‐3‐arylthioureas as Jack bean urease inhibitors

et al. 2017

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In this article, synthesis of a novel 1-(2-(4-isobutylphenyl)propanoyl)-3-arylthioureas (4a-j) as jack bean urease inhibitors has been described. Freshly prepared 2-(4-isobutylphenyl) propanoyl isothiocyanate was treated with substituted aromatic anilines in one pot using anhydrous acetone. The compounds 4e, 4h, and 4j showed IC values 0.0086 nm, 0.0081 nm, and 0.0094 nm, respectively. The enzyme inhibitory kinetics results showed that compound 4h inhibit the enzyme competitively while derivatives 4e and 4j are the mixed type inhibitors. The compound 4h reversibly binds the urease enzyme showing Ki value 0.0012 nm. The Ki values for 4e and 4j are 0.0025 nm and 0.003 nm, respectively. The antioxidant activity results reflected that compounds 4b, 4i, and 4j showed excellent radical scavenging activity. Moreover, the cytotoxic activity of the target compounds was evaluated using brine shrimp assay and it was found that all of the synthesized compounds exhibited no cytotoxic effects to brine shrimps. The computational molecular docking and molecular dynamic simulation of title compounds were also performed, and results showed that the wet laboratory findings are in good agreement to the dry laboratory results. Based upon our results, it is proposed that compound 4h may act as a lead candidate to design the clinically useful urease inhibitors.

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“…Very recently, we have reported the synthesis of novel xanthene based imine derivatives showing excellent antibacterial activity [18]. Inspired with biological activities possessed by imines [19][20][21][22][23] and amoxicillin, an endeavor was made to manufacture novel imine derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) of amoxicillin by condensing it with different aldehydes and ketones. The novel amoxicillin imine derivatives were characterized well by different spectroscopic techniques and screened for antimicrobial activities.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, characterization and antimicrobial studies of imine derivatives of amoxicillin

et al. 2015

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Some novel imine derivatives (1-14) of a broad spectrum antibiotic amoxicillin were prepared by condensation with different carbonyl compounds. The amoxicillin imine derivatives were characterized using elemental analysis and spectroscopic techniques such as FT-IR and 1 H NMR. The prepared imine derivatives were evaluated for antimicrobial activities against some pathogens using disc diffusion method. The results of present studies demonstrate enhanced antimicrobial activity of the novel imine derivatives of amoxicillin as compared to the parent drug.

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Synthesis, biological evaluation and molecular docking of N-phenyl thiosemicarbazones as urease inhibitors

Cited by 65 publications

References 36 publications

In Vitro, In Silico Elucidation of Antiurease Activity, Kinetic Mechanism and COX‐2 Inhibitory Efficacy of Coagulansin A of Withania coagulans

In Vitro, In Silico Elucidation of Antiurease Activity, Kinetic Mechanism and COX‐2 Inhibitory Efficacy of Coagulansin A of Withania coagulans

Synthesis, enzyme inhibitory kinetics, and computational studies of novel 1‐(2‐(4‐isobutylphenyl) propanoyl)‐3‐arylthioureas as Jack bean urease inhibitors

Synthesis, characterization and antimicrobial studies of imine derivatives of amoxicillin

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