Acridine-based (thio)semicarbazones and hydrazones: Synthesis, in vitro urease inhibition, molecular docking and in-silico ADME evaluation

Isaac, Ibanga O.; al‐Rashida, Mariya; Rahman, Shafiq Ur; Alharthy, Rima D.; Asari, Asnuzilawati; Hameed, Abdul; Khan, Khalid Mohammed; Iqbal, Jamshed

doi:10.1016/j.bioorg.2018.09.032

Cited by 19 publications

(10 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Isaac et al [208] . introduced acridine based hydrazones and (thio)semicarbazones as urease inhibitors and explained their binding mode via molecular docking studies.…”

Section: Biological Activity Of Acridinedione Derivativesmentioning

confidence: 99%

See 1 more Smart Citation

Acridine‐1,8‐diones: Synthesis and Biological Applications

Sahiba¹,

Sethiya²,

Soni³

et al. 2021

ChemistrySelect

View full text Add to dashboard Cite

The unpretentious features of acridine‐1,8‐diones viz. presence of N‐heteroatom, electronic behavior, acridine ring skeleton and wide possibilities of diversified substitution, bichromophoric structure and interaction ability with various proteins, make them an interesting scaffold of heterocyclic, medicinal and industrial chemistry. A tremendous development in the field of acridinediones in terms of synthetic strategies, bioactivity, industrial and other applicability has been explored in past four decades. In this perspective, an overview has been given on the state‐of‐art discoveries for the synthesis and biological applications of acridine‐1,8‐diones from 1980 to 2020. The study highlighted the history, chemistry and properties of these derivatives and provided deep insights into the synthetic protocols using various catalysts and techniques like nano‐catalyst, ionic‐liquids, microwave, ultrasound etc. under varied conditions along with biological activity against many lethal diseases. Finally, the respective prospects and limitations to these systems have been addressed. Furthermore, attempts have been done to bring many outstanding researches together and express the significance of acridine‐1,8‐diones through several aspects. We hope that the article shall deliver an impetus to explore further the synthetic values and mechanistic puzzles of acridinedione moiety and to design more promising hybrid multi‐targeted drugs and other industrial composites for the goodness of humanity

show abstract

“…Isaac et al [208] . introduced acridine based hydrazones and (thio)semicarbazones as urease inhibitors and explained their binding mode via molecular docking studies.…”

Section: Biological Activity Of Acridinedione Derivativesmentioning

confidence: 99%

“…Isaac et al [208] introduced acridine based hydrazones and (thio)semicarbazones as urease inhibitors and explained their binding mode via molecular docking studies. All the synthesized derivatives were active against urease enzyme and compounds 12 a and 12 b exhibited best inhibition.…”

Section: Biological Activity Of Acridinedione Derivativesmentioning

confidence: 99%

Acridine‐1,8‐diones: Synthesis and Biological Applications

Sahiba¹,

Sethiya²,

Soni³

et al. 2021

ChemistrySelect

View full text Add to dashboard Cite

show abstract

“…[10][11][12][13][14][15][16][17][18] It was also observed that different series of molecular structures showing close homology with urea/thiourea moiety, such as the (thio)semicarbazones, [19,20] N-phenyl thiosemicarbazones, [21] hydrazones [22] led to urease inhibitory activity. [23] The structure of some of the reported thiosemicarbazone derivatives as urease inhibitors is presented in Figure 1b.…”

Section: Introductionmentioning

confidence: 99%

“…The biological versatility of thiosemicarbazones as antimalarial, antibacterial, anticancer, antifungal, antitumor, and urease inhibitor made them multifaceted and potent agents [10–18] . It was also observed that different series of molecular structures showing close homology with urea/thiourea moiety, such as the (thio)semicarbazones, [19,20] N‐phenyl thiosemicarbazones, [21] hydrazones [22] led to urease inhibitory activity [23] . The structure of some of the reported thiosemicarbazone derivatives as urease inhibitors is presented in Figure 1b.…”

Section: Introductionmentioning

confidence: 99%

Thiosemicarbazone Derivatives Act as Potent Urease Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study

et al. 2022

View full text Add to dashboard Cite

An enzyme called urease assists highly pathogenic bacteria in colonizing and maintaining themselves. Accordingly, inhibiting urease enzymes has been shown to be a promising strategy for preventing ureolytic bacterial infections. So, design and synthesis of potent and safe urease inhibitors converted to an interesting target for medicinal chemists. In this study, the design, synthesis, and bioactivity of fourteen thiosemicarbazone derivatives 5 a-n are described as potent urease inhibitors. A variety of spectroscopic techniques ( 1 H-NMR, 13 C-NMR, MS), and elemental analysis were utilized to determine the structure of 5 a-n. Interestingly, all 5 a-n showed higher inhibitory activity (IC 50 : 4.08 to 11.31 μM) than the standards thiourea and hydroxyurea (IC 50 : 22 and 100 μM respectively). 5 g and 5 f exhibited the best activity with IC 50 values of 4.08 and 4.79 μM, respectively. Molecular docking was also used to reveal the potential interactions between the enzyme's active site and the most active compound. An MTT assay was conducted on two different cell lines to investigate the cytotoxic effect of the tested compounds. all 5 a-n have IC 50 values above 50 μM on both tested cell lines. In conclusion, current reported compounds are potent and safe enough to continue further bioassays to find a new drug candidate.

show abstract

“…The inhibition of urease has been reported by using different heterocycles. In their studies, Iqbal et al have reported 1,3-thiazoles (Channar et al, 2021), benzohydrazide derivatives (Abbas S. et al, 2019), acridine-based (thio)semicarbazones, hydrazones (Isaac et al, 2019), and semicarbazones derivatives (Qazi et al, 2018) as urease inhibitors. The copper metal ion containing tyrosinase has been known to be involved in melanin biosynthesis.…”

mentioning

confidence: 99%

Editorial: Metalloenzymes: Potential Drug Targets

2021

Self Cite

View full text Add to dashboard Cite

Editorial on the Research Topic Metalloenzymes: Potential Drug TargetsMetalloenzymes have an important role in the regulation of many biological functions. Overexpressed and/or reduced secretion of such enzymes lead to different complications of clinical interest. The metal ions present in enzymes control the structure, folding, and functions of such proteins. The protein data bank (PDB) revealed that over 50% of proteins contain metal ions (Solomon et al., 1996). The development of metalloenzyme inhibitors are of interest in the treatment of various diseases. The interaction of ligands, i.e., compounds as inhibitors with target proteins via active sites provide a means of curing diseases. Most aptly, the inhibitors reported by academic or pharmaceutical usage of small molecules as inhibitors provide a rapid and viable way to treat diseases. Urease is a ubiquitous metalloenzyme, produced by various cell types from plants, fungi, and bacteria, etc., that bears a nickel atom in its active pocket. It hydrolyzes the urea into ammonia and carbamate which further decompose to ammonia and CO 2 . The overexpression of urease was known to be linked with ulcers, hepatic coma, and formation of urinary stones (Upadhyay, 2012;Kappaun et al., 2018).Carbonic anhydrase with zinc metal ion catalyze the hydration of CO 2 with water to produce hydrogen carbonate and H + ions (Alvarez-Leefmans and Delpire, 2009). The hydration reaction involves the nucleophilic attack of the metal-bounded hydroxy (OH) group with the carbon (C) atom of carbon dioxide species (Silverman and Lindskog, 1988). The coordination of carbonic anhydrases (CAs) with metal ion occurs at active sites via binding with histidine, cysteine, and/or glutamine residues to form a tetrahedral shape (Steiner et al., 1975). The inhibitors of CAs have been employed as diuretic and antiglaucoma agents as well as anti-obesity and anticancer agents (Supuran, 2008).Furthermore, ubiquitous ecto-nucleotidases such as 1) nucleoside triphosphate diphosphohydrolases (NTPDases), 2) nucleotide pyrophosphatase/phosphodiesterases (NPPs), 3) alkaline phosphatases (APs or ALPs), and 4) ecto-5′-nucleotidase (e5′NT) are all responsible for the integrity of proper cell functioning (Supuran, 2008). The NPPs possess zinc (Zn 2+ ) metal ion at active sites while the e5′NT has additionally magnesium ion (Mg 2+ ) at the active site. The overexpression of surface-located ecto-enzymes hydrolyzing nucleotides causes various complications which affect different functions such as cell proliferation, apoptosis as well as degenerative, neurological, and immunological responses. In the current issue, Baqi et al. reported the use of anthraquinone derivatives as NTPDase inhibitors which showed selectivity towards NTPDase2 and -3. The compound, 1-amino-4-(9-phenanthrylamino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate, with an IC 50 value of 539 nM was found to be a potent inhibitor of NTPDase2, while the anthraquinone, 1-amino-4-[3-(4,6-dichlorotriazin-2-ylamino)-4-sulfophenylamino]-9,10-dioxo-

show abstract

Acridine-based (thio)semicarbazones and hydrazones: Synthesis, in vitro urease inhibition, molecular docking and in-silico ADME evaluation

Cited by 19 publications

References 34 publications

Acridine‐1,8‐diones: Synthesis and Biological Applications

Acridine‐1,8‐diones: Synthesis and Biological Applications

Thiosemicarbazone Derivatives Act as Potent Urease Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study

Editorial: Metalloenzymes: Potential Drug Targets

Contact Info

Product

Resources

About