A novel class of phenylpyrazolone-sulphonamides rigid synthetic anticancer molecules selectively inhibit the isoform IX of carbonic anhydrases guided by molecular docking and orbital analyses

Khayat, Maan T.; Ahmed, Hany E. A.; Omar, Abdelsattar M.; Muhammad, Yosra A.; Mohammad, Khadijah A.; Malebari, Azizah M.; Khayyat, Ahdab N.; Halawa, Ahmed H.; Abulkhair, Hamada S.; Al‐Karmalawy, Ahmed A.; Almaghrabi, Mohammed; Alharbi, Majed; Aljahdali, Anfal S.; El‐Agrody, Ahmed M.

doi:10.1080/07391102.2023.2188957

Cited by 11 publications

(3 citation statements)

References 77 publications

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“…The human DNA in complex with Topo I (1T8I) and Topo II (3QX3) target receptors were extracted. Each target protein was prepared for docking as reported previously 62 . Then, two docking processes were accomplished using the corresponding database and following the default setting options and methodology as before 9 .…”

Section: Methodsmentioning

confidence: 99%

Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers

El-Kalyoubi,

Khalifa,

Abo-Elfadl

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation of spirooxindoles and pyrimidines. In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised. The targets and the SeNP derivatives were examined for their cytotoxicity towards five cancer cell lines. The inhibitory potencies of the best members against Topo I and Topo II were also assayed besides their DNA intercalation abilities. Compound 7d NPs exhibited the best inhibition against Topo I and Topo II enzymes with IC 50 of 0.042 and 1.172 μM, respectively. The ability of compound 7d NPs to arrest the cell cycle and induce apoptosis was investigated. It arrested the cell cycle in the A549 cell at the S phase and prompted apoptosis by 41.02% vs. 23.81% in the control. In silico studies were then performed to study the possible binding interactions between the designed members and the target proteins.

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Section: Methodsmentioning

confidence: 99%

Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers

El-Kalyoubi,

Khalifa,

Abo-Elfadl

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Against hCA II, 561p (Ar = 3‐OH‐4MeOC 6 H 3 ) and 561r showed good activity against hCA II with IC 50 value of 0.107 ± 0.01 and 0.089 ± 0.01 µM, respectively, as compared to AAZ (IC 50 = 0.256 ± 0.01 µM). Compound 561p showed potent activity against hCA IX with IC 50 value of 0.033 ± 0.01 µM as compared to AAZ (IC 50 = 0.045 µM) [ 104 ] (Scheme 86).…”

Section: Chemistry Of Heterocycles As Ca Inhibitorsmentioning

confidence: 99%

Chemistry of heterocycles as carbonic anhydrase inhibitors: A pathway to novel research in medicinal chemistry review

Bendi,

Taruna,

Rajni

et al. 2024

Archiv der Pharmazie

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Nowadays, the scientific community has focused on dealing with different kinds of diseases by exploring the chemistry of various heterocycles as novel drugs. In this connection, medicinal chemists identified carbonic anhydrases (CA) as one of the biologically active targets for curing various diseases. The widespread distribution of these enzymes and the high degree of homology shared by the different isoforms offer substantial challenges to discovering potential drugs. Medicinal and synthetic organic chemists have been continuously involved in developing CA inhibitors. This review explored the chemistry of different heterocycles as CA inhibitors using the last 11 years of published research work. It provides a pathway for young researchers to further explore the chemistry of a variety of synthetic as well as natural heterocycles as CA inhibitors.

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“…One strategy for the design of a suggested drug candidate is to combine two pharmacophoric fragments of more than one well-known bioactive molecule belonging to a specific therapeutic class in one new scaffold [ 30 , 31 , 32 , 33 ]. For example, 1,2,3-triazole-based heterocycles were perfectly applied to develop numerous scaffolds with potent antiviral activity [ 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Phenylpyrazolone-1,2,3-triazole Hybrids as Potent Antiviral Agents with Promising SARS-CoV-2 Main Protease Inhibition Potential

et al. 2023

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COVID-19 infection is now considered one of the leading causes of human death. As an attempt towards the discovery of novel medications for the COVID-19 pandemic, nineteen novel compounds containing 1,2,3-triazole side chains linked to phenylpyrazolone scaffold and terminal lipophilic aryl parts with prominent substituent functionalities were designed and synthesized via a click reaction based on our previous work. The novel compounds were assessed using an in vitro effect on the growth of SARS-CoV-2 virus-infested Vero cells with different compound concentrations: 1 and 10 μM. The data revealed that most of these derivatives showed potent cellular anti-COVID-19 activity and inhibited viral replication by more than 50% with no or weak cytotoxic effect on harboring cells. In addition, in vitro assay employing the SARS-CoV-2-Main protease inhibition assay was done to test the inhibitors’ ability to block the common primary protease of the SARS-CoV-2 virus as a mode of action. The obtained results show that the one non-linker analog 6h and two amide-based linkers 6i and 6q were the most active compounds with IC50 values of 5.08, 3.16, and 7.55 μM, respectively, against the viral protease in comparison to data of the selective antiviral agent GC-376. Molecular modeling studies were done for compound placement within the binding pocket of protease which reveal conserved residues hydrogen bonding and non-hydrogen interactions of 6i analog fragments: triazole scaffold, aryl part, and linker. Moreover, the stability of compounds and their interactions with the target pocket were also studied and analyzed by molecular dynamic simulations. The physicochemical and toxicity profiles were predicted, and the results show that compounds behave as an antiviral activity with low or no cellular or organ toxicity. All research results point to the potential usage of new chemotype potent derivatives as promising leads to be explored in vivo that might open the door to rational drug development of SARS-CoV-2 Main protease potent medicines.

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A novel class of phenylpyrazolone-sulphonamides rigid synthetic anticancer molecules selectively inhibit the isoform IX of carbonic anhydrases guided by molecular docking and orbital analyses

Cited by 11 publications

References 77 publications

Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers

Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers

Chemistry of heterocycles as carbonic anhydrase inhibitors: A pathway to novel research in medicinal chemistry review

Phenylpyrazolone-1,2,3-triazole Hybrids as Potent Antiviral Agents with Promising SARS-CoV-2 Main Protease Inhibition Potential

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