Evaluation of sulfonate and sulfamate derivatives possessing benzofuran or benzothiophene nucleus as inhibitors of nucleotide pyrophosphatases/phosphodiesterases and anticancer agents

Anbar, Hanan S.; El-Gamal, Randa; Ullah, Saif; Zaraei, Seyed–Omar; al‐Rashida, Mariya; Zaib, Sumera; Pelletier, Julie; Sévigny, Jean; Iqbal, Jamshed; El–Gamal, Mohammed I.

doi:10.1016/j.bioorg.2020.104305

Cited by 14 publications

(6 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The compound 70 showed the most cytotoxic effect against MCF-7 cell lines with an IC 50 value of 0.19 μM. [105] The novel benzothiophene diaryl urea derivatives were designed and synthesized as potent anticancer agents against HT-29 and A549. The final derivatives were synthesized by reaction of 5-nitro-benzothiophene-2carbonyl chloride and p-hydroxy diacetyl urea derivatives in the presence of base triethylamine.…”

Section: Benzothiophene Derivatives As Anticancer Agentsmentioning

confidence: 99%

Anticancer Potential of the S‐Heterocyclic Ring Containing Drugs and its Bioactivation to Reactive Metabolites

Maji,

Debnath,

Panda

et al. 2024

Chemistry & Biodiversity

View full text Add to dashboard Cite

Sulfur‐containing heterocyclic derivatives have been disclosed for binding with a wide range of cancer‐specific protein targets. Various interesting derivatives of sulfur‐containing heterocyclics such as benzothiazole, thiazole, thiophene, thiazolidinedione, benzothiophene, and phenothiazine, etc have been shown to inhibit diverse signaling pathways implicated in cancer. Significant progress has also been made in molecular targeted therapy against specific enzymes such as kinase receptors due to potential binding interactions inside the ATP pocket. Sulfur‐containing heterocyclic ring metal complexes i.e., benzothiazole, thiazole, thiophene, benzothiophene and phenothiazines are among the most promising active anticancer compounds. However, sulfur heteroaromatic rings, particularly thiophene, are of high structural alert due to their metabolism to reactive metabolites. The mere presence of a structural alert itself does not determine compound toxicity therefore, this review focuses on some specific findings that shed light on factors influencing the toxicity. In the current review, synthetic strategies of introducing the sulfur core ring in the synthesized derivatives are discussed with their structure‐activity relationships to enhance our understanding of toxicity mechanisms and develop safer therapeutic options. The sulfur‐containing marketed anticancer drugs included in this review direct the synthesis of novel compounds and will help in the development of potent, safer sulfur‐based anticancer drugs in near future.

show abstract

Section: Benzothiophene Derivatives As Anticancer Agentsmentioning

confidence: 99%

Anticancer Potential of the S‐Heterocyclic Ring Containing Drugs and its Bioactivation to Reactive Metabolites

Maji,

Debnath,

Panda

et al. 2024

Chemistry & Biodiversity

View full text Add to dashboard Cite

show abstract

“…Several structures with sulphonate moiety are reported to possess therapeutic importance such as suramin (Figure ) with a complex structure and poly sulphonate groups, being widely used as a positive control of choice in different biological studies . In the previous study, we have reported pyrrolo[2,3- b ]pyridine derivatives such as ( N -(pyrrolo[2,3- b ]pyridine-1-carbonyl)benzenesulfonamide), which was found as a selective inhibitor of ENPP1 with an IC 50 value of 4.50 ± 0.16 μM and carbohydrazide-based derivative, which selectively blocked the activity of ENPP3 to half of the maximal value of 0.15 μM. , Various previously reported structures with sulphonate scaffolds including raloxifene sulphonates, benzofuran, and benzothiophene sulphonates exhibited significant enzyme inhibitory activity to sub-micromolar levels, for example, raloxifene sulphonate derivative 3-(4-(2-(piperidin-1-yl)ethoxy)benzoyl)-2-(4-(tosyloxy)phenyl)benzo[ b ]thiophen-6-yl-4-methylbenzenesulfonate tabulated selective inhibition of isozyme ENPP1 to an IC 50 value of 0.45 μM, and benzothiophene derivative (4-(benzo[ b ]thiophen-5-yl)phenyl cyclohexanesulfonate) was endowed with IC 50 = 0.12 μM against ENPP1 and 1.89 μM toward ENPP3. , We have also reported sulphonate derivatives mainly based on non-aromatic or saturated cyclic hydrocarbons. These structures exhibited considerable inhibitory activity but limited preferable selectivity among the three isozymes ENPP1, ENPP2, and ENPP3 …”

Section: Introductionmentioning

confidence: 99%

“…22,23 Various previously reported structures with sulphonate scaffolds including raloxifene sulphonates, benzofuran, and benzothiophene sulphonates exhibited significant enzyme inhibitory activity to sub-micromolar levels, for example, raloxifene sulphonate derivative 3- nesulfonate tabulated selective inhibition of isozyme ENPP1 to an IC 50 value of 0.45 μM, and benzothiophene derivative (4-(benzo[b]thiophen-5-yl)phenyl cyclohexanesulfonate) was endowed with IC 50 = 0.12 μM against ENPP1 and 1.89 μM toward ENPP3. 24,25 We have also reported sulphonate derivatives mainly based on non-aromatic or saturated cyclic hydrocarbons.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Arylamide Sulphonate Derivatives as Ectonucleotide Pyrophosphatase/Phosphodiesterase-1 and -3 Inhibitors

et al. 2022

Self Cite

View full text Add to dashboard Cite

Aberrant level of ectonucleotide pyrophosphatase/phosphodiesterase-1 and -3 is linked with numerous disorders, for instance, diabetes, cancer, osteoarthritis, chondrocalcinosis, and allergic reactions. These disorders may be cured or minimized by blocking the activity of ENPP1 and ENPP3 isozymes. In this study, arylamide sulphonates were synthesized, characterized, and evaluated for their capability to affect the activity of isozymes ENPP1 and ENPP3. Among the selective inhibitors of ENPP1, compounds 4f and 4q exhibited sub-micromolar IC 50 values of 0.28 ± 0.08 and 0.37 ± 0.03 μM, respectively, followed by 7a , with IC 50 equal to 0.81 ± 0.05 μM, whereas out of the selective inhibitors of isozyme ENPP3, 4t and 7d preferably lessened the activity to half of the maximal inhibitory concentration of 0.15 ± 0.04 and 0.16 ± 0.01 μM alternatively. In addition, many structures including 4c , 4g , 4k , 4l , 4n , 4o , 4r , 4s , 7b , 7c , and 7e inhibited the activity of both isozymes to a significant level. Enzyme kinetic study of compound 4j revealed an uncompetitive mode of inhibition of ENPP1 isozyme, while 7e competitively blocked the activity of ENPP3. Cell viability analysis revealed the compound 4o as a cytotoxic agent against MCF7 (human breast cancer cell line) with a percentage inhibition of 63.2 ± 2.51%, whereas compounds 4c , 4d , 4n , and 7d decreased the HeLa cell viability (human cervical cancer cell line) to more than 50%. The tested compounds were non-cytotoxic against HEK293 (a human embryonic kidney cell line). Molecular docking analysis of selected inhibitors of both isozymes produced optimistic interactions with the influential amino acids, such as Leu290, Lys295, Tyr340, Asp376, His380, and Pro323 of ENPP1, whereas residues Asn226, His329, Leu239, Tyr289, Pro272, Tyr320, and Ala205 of ENPP3 crystallographic structure formed interactions with the potent inhibitors.

show abstract

“…Aryl sulfonate ester linkages frequently exist in various natural products [1] . The bioactive properties of these compounds have made them interesting targets for chemists [2–8] . Recently, the synthesis, characterization, and antidiabetic potentials of novel aryl sulfonyloxy‐5‐arylidene thiazolidine‐2,4‐dione analogs were evaluated by Mehta and Mahapatra [9] .…”

Section: Introductionmentioning

confidence: 99%

“…[1] The bioactive properties of these compounds have made them interesting targets for chemists. [2][3][4][5][6][7][8] Recently, the synthesis, characterization, and antidiabetic potentials of novel aryl sulfonyloxy-5arylidene thiazolidine-2,4-dione analogs were evaluated by Mehta and Mahapatra. [9] Also, a new series of pyrazole N-aryl sulfonate have been reported and their potential cyclooxygenase-2 selective inhibitory properties were investigated as well.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Biological Activity and Molecular Docking Studies of Novel Sulfonate Derivatives Bearing Salicylaldehyde

Korkmaz

Bursal

2022

Chemistry & Biodiversity

View full text Add to dashboard Cite

Enzyme activity alterations have been associated with many metabolism disorders and have crucial roles in the pathogenesis of some diseases. Tyrosinase is a key enzyme in melanin biosynthesis, which is responsible for skin pigmentation to protect the skin from solar radiation. Pancreatic lipase has been considered a key enzyme for the treatment of obesity. Herein, we reported the synthesis and enzyme inhibitions of a series of sulfonates as possible tyrosinase and pancreatic lipase inhibitors. According to the calculated IC50 values, compound 3f (74.1±11.1 μM) and compound 3c (86.6±6.9 μM) were determined to be the best inhibitors among the synthesized compounds for the tyrosinase and pancreatic lipase enzymes, respectively. The approach yielded at extremely high level by creating very flexible structural domains for the chemically modified groups. The structural characterization of the target molecules was implemented by 1H‐NMR, 13C‐NMR, and HR‐MS analyses. Also, molecular docking studies of the synthesized compounds with tyrosinase and pancreatic lipase enzymes were conducted using AutoDock Vina software. Additionally, the studies of the absorption distribution, metabolism, and excretion (ADME) were performed to uncover the target compounds′ pharmacokinetics, drug similarities, and medicinal properties of the novel sulfonate derivatives bearing salicylaldehyde.

show abstract

Evaluation of sulfonate and sulfamate derivatives possessing benzofuran or benzothiophene nucleus as inhibitors of nucleotide pyrophosphatases/phosphodiesterases and anticancer agents

Cited by 14 publications

References 54 publications

Anticancer Potential of the S‐Heterocyclic Ring Containing Drugs and its Bioactivation to Reactive Metabolites

Anticancer Potential of the S‐Heterocyclic Ring Containing Drugs and its Bioactivation to Reactive Metabolites

Synthesis and Biological Evaluation of Arylamide Sulphonate Derivatives as Ectonucleotide Pyrophosphatase/Phosphodiesterase-1 and -3 Inhibitors

Synthesis, Biological Activity and Molecular Docking Studies of Novel Sulfonate Derivatives Bearing Salicylaldehyde

Contact Info

Product

Resources

About