Diarylsulfonamides and their bioisosteres as dual inhibitors of alkaline phosphatase and carbonic anhydrase: Structure activity relationship and molecular modelling studies

al‐Rashida, Mariya; Ejaz, Syeda Abida; Ali, Sharafat; Shaukat, Aisha; Hamayoun, Mehwish; Ahmed, Maqsood; Iqbal, Jamshed

doi:10.1016/j.bmc.2015.03.054

Cited by 44 publications

(26 citation statements)

References 35 publications

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“…In the docking model with bovine tissue‐non‐specific alkaline phosphatase, the most potent compound 3g formed hydrogen bonding interactions with the catalytic Ser110 and with residue His338. Residues Arg184 and His451 also formed hydrogen bonding interactions with the inhibitor, consistent with previously observed interactions . Residue His451 interacted with the pyridine ring of the compound.…”

Section: Resultssupporting

confidence: 87%

Isonicotinohydrazones as inhibitors of alkaline phosphatase and ecto‐5′‐nucleotidase

et al. 2016

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A series of isonicotinohydrazide derivatives was synthesized and tested against recombinant human and rat ecto-5'-nucleotidases (h-e5'NT and r-e5'NT) and alkaline phosphatase isozymes including both bovine tissue-non-specific alkaline phosphatase (b-TNAP) and tissue-specific calf intestinal alkaline phosphatase (c-IAP). These enzymes are implicated in vascular calcifications, hypophosphatasia, solid tumors, and cancers, such as colon, lung, breast, pancreas, and ovary. All tested compounds were active against both enzymes. The most potent inhibitor of h-e5'NT was derivative (E)-N'-(1-(3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)ethylidene)isonicotinohydrazide (3j), whereas derivative (E)-N'-(4-hydroxy-3-methoxybenzylidene)isonicotinohydrazide (3g) exhibited significant inhibitory activity against r-e5'NT. In addition, the derivative (E)-N'-(4'-chlorobenzylidene)isonicotinohydrazide (3a) was most potent inhibitor against calf intestinal alkaline phosphatase and the derivative (E)-N'-(4-hydroxy-3-methoxybenzylidene)isonicotinohydrazide (3g) was found to be most potent inhibitor of bovine tissue-non-specific alkaline phosphatase. Furthermore, putative binding modes of potent compounds against e5'NT (human and rat e5'NT) and AP (including b-TNAP and c-IAP) were determined computationally.

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Section: Resultssupporting

confidence: 87%

Isonicotinohydrazones as inhibitors of alkaline phosphatase and ecto‐5′‐nucleotidase

et al. 2016

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“…In Figure , Arg335, His338, His341, His451 and His454 amino acid residues of the b‐TNAP protein supported the functional conformation and ligand binding, while, in Figure , Arg106, His339 and His451 amino acid residues of the c‐IAP protein supported the functional conformation and ligand binding. These modes of orientation of inhibitors were in agreement with the reported binding interaction inside the active site of both b‐TNAP and c‐IAP . Detailed analysis of binding orientation of three stereoisomers of compound 4 o in Figure showed that two stereoisomers of compound 4 o , namely (meso)‐ 4 o and (S,R)‐ 4 o , formed three strong hydrogen bonds.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Alkynylated Dihydrofuran‐2(3H)‐ones as Potent and Selective Inhibitors of Tissue Non‐Specific Alkaline Phosphatase

et al. 2017

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The synthesis of new derivatives of 3‐(3‐arylprop‐2‐ynyl)dihydrofuran‐2(3H)‐ones by Sonogashira reactions and their screening as potent and selective inhibitors of b‐TNAP is reported. Although a few derivatives exhibited non‐selective inhibition of c‐IAP, most of the derivatives were found to be potent and selective inhibitors of b‐TNAP. The selective and potent inhibitors of b‐TNAP might be useful for the treatment of vascular calcification. Among the derivatives studied, one compound was identified as the most potent inhibitor of b‐TNAP with a high inhibitory value, exhibiting a 6 fold more selective activity towards b‐TNAP as compared to c‐IAP. The higher inhibitory activity of this compound towards b‐TNAP is caused by the presence of two furan rings. Similarly, another derivative, having a furan ring, exhibited a lower inhibitory potential towards b‐TNAP, but this compound was found to be the most potent inhibitor of c‐IAP. Furthermore, molecular docking studies of these potent compounds were carried out to see the possible binding modes of potent inhibitors inside the active pocket of respective enzyme.

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“…Nicotine (Scharlau Laboratory, Spain) was dissolved in 0.9% normal saline, whereas 4-fluoro-N-(4-sulfamoylbenzyl) benzene-sulfonamide was provided by Dr. Mariya Al Rashida, 37 that was prepared as a suspension using 5% dimethyl sulfoxide (DMSO). The solutions and suspensions were freshly prepared daily.…”

Section: Methodsmentioning

confidence: 99%

<p>Effect of 4-Fluoro-N-(4-Sulfamoylbenzyl) Benzene Sulfonamide on Acquisition and Expression of Nicotine-Induced Behavioral Sensitization and Striatal Adenosine Levels</p>

Rehman¹,

Abbas²,

al‐Rashida³

et al. 2020

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Introduction Behavioral sensitization is a phenomenon that develops from intermittent exposure to nicotine and other psychostimulants, which often leads to heightened locomotor activity and then relapse. Sulfonamides that act as carbonic anhydrase inhibitors have a documented role in enhancing dopaminergic tone and normalizing neuroplasticity by stabilizing glutamate release. Objective The aim of the current study was to explore synthetic sulfonamides derivative 4-fluoro-N-(4-sulfamoylbenzyl) benzene-sulfonamide (4-FBS) (with documented carbonic anhydrase inhibitory activity) on acquisition and expression of nicotine-induced behavioral sensitization. Methods In the acquisition phase, selected 5 groups of mice were exposed to saline or nicotine 0.5mg/kg intraperitoneal (i.p) for 7 consecutive days. Selected 3 groups were administered with 4-FBS 20, 40, and 60 mg/kg p.o. along with nicotine. After 3 days of the drug-free period, ie, day 11, a challenge dose of nicotine was injected to all groups except saline and locomotor activity was recorded for 30 minutes. In the expression phase, mice were exposed to saline and nicotine only 0.5 mg/kg i.p for 7 consecutive days. After 3 days of the drug-free period, ie, day 11, 4-FBS at 20, 40, and 60 mg/kg were administered to the selected groups, one hour after drug a nicotine challenge dose was administered, and locomotion was recorded. At the end of behavioral experiments, all animals were decapitated and the striatum was excised and screened for changes in adenosine levels, using HPLC-UV. Results Taken together, our findings showed that 4-FBS in all 3 doses, in both sets of experiments significantly attenuated nicotine-induced behavioral sensitization in mice. Additionally, 4-FBS at 60mg/kg significantly lowered the adenosine level in the striatum. Conclusion The behavioral and adenosine modulation is promising, and more receptors level studies are warranted to explore the exact mechanism of action of 4-FBS.

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Diarylsulfonamides and their bioisosteres as dual inhibitors of alkaline phosphatase and carbonic anhydrase: Structure activity relationship and molecular modelling studies

Cited by 44 publications

References 35 publications

Isonicotinohydrazones as inhibitors of alkaline phosphatase and ecto‐5′‐nucleotidase

Isonicotinohydrazones as inhibitors of alkaline phosphatase and ecto‐5′‐nucleotidase

Synthesis of Alkynylated Dihydrofuran‐2(3H)‐ones as Potent and Selective Inhibitors of Tissue Non‐Specific Alkaline Phosphatase

<p>Effect of 4-Fluoro-N-(4-Sulfamoylbenzyl) Benzene Sulfonamide on Acquisition and Expression of Nicotine-Induced Behavioral Sensitization and Striatal Adenosine Levels</p>

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