Novel hybrid isoindole‐1,3(2<i>H</i>)‐dione compounds containing a 1<i>H</i>‐tetrazole moiety: Synthesis, biological evaluation, and molecular docking studies

Tan, Ayşe; Kizilkaya, Serap; Noma, Samir Abbas Ali; Ateş, Burhan; Kara, Yunus

doi:10.1002/jbt.23015

Cited by 9 publications

(8 citation statements)

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“…The substituted isoindoles have significant therapeutic potential and remain a long-standing focus of dynamic scientific interest. It is a large group of salutary agents showing anti-HIV [1], anticancer [2], antipsychotic [3], antianxiety [4,5], antiinflammatory [6], antimicrobial [7,8], antiarrhythmic [9] and anticonvulsant [10] activities. The molecular modification and derivatization of available drugs have led to enormously improved medicines.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Crystal Structure, DFT Calculations, Hirshfeld Surface Analysis and In Silico Drug-Target Profiling of (R)-2-(2-(1,3-Dioxoisoindolin-2-yl)propanamido)benzoic Acid Methyl Ester

et al. 2023

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The work here reflects synthesis, DFT studies, Hirshfeld charge analysis and crystal data exploration of pharmacologically important (R)-2-(2-(1,3-dioxoisoindolin-2-yl)propanamido)benzoic acid methyl ester (5) to understand its properties for further chemical transformations. The methyl anthranilate (2) was produced by the esterification of anthranilic acid in an acidic medium. The phthaloyl-protected alanine (4) was rendered by the fusion of alanine with phthalic anhydride at 150 °C, followed by coupling with (2) furnished isoindole (5). The characterization of products was performed using IR, UV-Vis, NMR and MS. Single-crystal XRD also verified the structure of (5) in which N-H…O bonding stabilizes the molecular configuration of (5), resulting in the formation of S(6) hydrogen-bonded loop. The molecules of isoindole (5) are connected in the form of dimers, and the π…π stacking interaction between aromatic rings further stabilizes the crystal packing. DFT studies suggest that HOMO is over the substituted aromatic ring, the LUMO is present mainly over the indole side, and nucleophilic and electrophilic corners point out the reactivity of the product (5). In vitro and in silico analysis of (5) shows its potential as an antibacterial agent targeting DNA gyrase and Dihydroorotase from E. coli and tyrosyl-tRNA synthetase and DNA gyrase from Staphylococcus aureus.

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Section: Introductionmentioning

confidence: 99%

Synthesis, Crystal Structure, DFT Calculations, Hirshfeld Surface Analysis and In Silico Drug-Target Profiling of (R)-2-(2-(1,3-Dioxoisoindolin-2-yl)propanamido)benzoic Acid Methyl Ester

et al. 2023

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“…This moiety has been described as multitarget structure with different biological effects, and many compounds of this scaffold are effective antimicrobial(4), anti-in ammatory(5) (6), anticonvulsant (7) (8), anti-viral (9), antioxidant (10),Xanthine oxidase inhibitors (11), and carbonic anhydrase inhibitors (11).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Biological Evaluation of Gabapentinoid Hybrids with Isoindole-1,3-(2H) Dione Moiety as potential antioxidant, antimicrobial, and anticancer

Jabbour,

Al-Khayat,

Murad

et al. 2023

Preprint

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Purpose: To synthesize new Isoindole-1,3-(2H) Dione derivatives by molecular hybridization of Gabapentin, and Pregabalin with phthalic anhydride derivatives, and to evaluate their biological activity as promising antioxidant, antimicrobial, and anticancer agents. Method: Molecular hybridization was successfully achieved by two procedures; synthesized compounds were characterized using analytical and spectral methods. Free radical scavenging properties of synthesized compounds were evaluated using DPPH method. Antibacterial activity of synthesized compounds, and parent compounds was evaluated against two microbial gram-positive and gram-negative strains by well diffusion method. Furthermore, we have studied effect of compounds on proliferation, cell cycle and cell death of two human cancer cell lines (Caco-2 and HCT-116). Results: Compounds 1,3,4 exhibited good free radical scavenging effect, compound 3 is the most effective with IC50 value 2.525 µmol/mL. All Compounds showed antibacterial activity against E. coli and Staphylococcus Aureus related to concentration while parent drugs did not exhibit any antibacterial effect. Compounds 1 and 2 showed good zone of inhibition against Escherichia Coli at micromolar concentrations, and they are more effective than gentamycin sulfate. Treatment with studied compounds suppresses proliferation, arrests progress throughout the cell cycle and induces apoptosis in Caco-2 and HCT-116 cancer cells. Compound 2 is highly effective against Caco-2 cells and more effective than Thalidomide, with IC50 value less than 1 µmol/L. Conclusion: Our results showed that molecular hybridization of Gabapentin, and Pregabalin in Isoindole-1,3(2H) Dione moiety result in promising anti-cancer and antimicrobial molecules. Results of this preliminary study show that halogenation of Isoindole-1,3-(2H) dione moiety improves antimicrobial, and anticancer activity, and that tetra-brominated derivatives are comparable or more effective than related tetra-chlorinated derivatives.

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“…Among heterocyclic scaffolds, isoindole-1,3(2H)-dione is of particular interest in drug discovery and drug development. This moiety has been described as a multitarget structure with different biological effects, and many compounds of this scaffold are effective antimicrobial (4), antiinflammatory agents (5), (6), anticonvulsants (7), (8), anti-virals (9), antioxidants (10), xanthine oxidase inhibitors (11), and carbonic anhydrase inhibitors (11). Many compounds of this moiety are effective for the treatment of Leishmania (12), diabetes (13) (14), hyperlipidemia (13) (15), cancer (16) (17) (18) (10), and Alzheimer (19) (20) (21).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Biological Evaluation of Gabapentinoid Hybrids with Isoindole-1,3(2H)-dione Moiety as Potential Antioxidant, Antimicrobial, and Anticancer Agents

Jabbour,

Al-Khayat,

Ktaifani

2023

Preprint

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Purpose: To synthesize new isoindole-1,3(2H)-dione derivatives by molecular hybridization of gabapentin, and pregabalin with phthalic anhydride derivatives, and to evaluate their biological activity as promising antioxidant, antimicrobial, and anticancer agents. Method: Molecular hybridization was successfully achieved by two procedures; synthesized compounds were characterized using analytical and spectral methods. The free radical scavenging properties of synthesized compounds were evaluated using the DPPH method. The antibacterial activity of synthesized compounds, and parent compounds was evaluated against two microbial gram-positive and gram-negative strains by the well diffusion method. Furthermore, we have studied the effect of compounds on proliferation, cell cycle, and cell death in two human cancer cell lines (Caco-2 and HCT-116). Results: Compounds 1, 3, and 4 exhibited a good free radical scavenging effect, compound 3 is the most effective with IC50 value 2.525 µmol/mL. All Compounds showed antibacterial activity against E. coli and Staphylococcus Aureus related to concentration, while parent drugs did not exhibit any antibacterial effect. Compounds 1 and 2 showed a good zone of inhibition against Escherichia Coli at micromolar concentrations, and they are more effective than gentamycin sulfate. Treatment with the studied compounds suppresses proliferation, arrests progress throughout the cell cycle, and induces apoptosis in Caco-2 and HCT-116 cancer cells. Compound 2 is highly effective against Caco-2 cells and more effective than Thalidomide, with IC50 value less than 1 µmol/L. Conclusion: Our results showed that molecular hybridization of gabapentin and Pregabalin in the isoindole-1,3(2H)-dione moiety results in promising anti-cancer and antimicrobial molecules. Results of this preliminary study show that halogenation of the isoindole-1,3(2H)-dione moiety improves antimicrobial and anticancer activity and that tetra-brominated derivatives are comparable to or more effective than related tetra-chlorinated derivatives.

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Novel hybrid isoindole‐1,3(2H)‐dione compounds containing a 1H‐tetrazole moiety: Synthesis, biological evaluation, and molecular docking studies

Cited by 9 publications

References 58 publications

Synthesis, Crystal Structure, DFT Calculations, Hirshfeld Surface Analysis and In Silico Drug-Target Profiling of (R)-2-(2-(1,3-Dioxoisoindolin-2-yl)propanamido)benzoic Acid Methyl Ester

Synthesis, Crystal Structure, DFT Calculations, Hirshfeld Surface Analysis and In Silico Drug-Target Profiling of (R)-2-(2-(1,3-Dioxoisoindolin-2-yl)propanamido)benzoic Acid Methyl Ester

Synthesis, Characterization, and Biological Evaluation of Gabapentinoid Hybrids with Isoindole-1,3-(2H) Dione Moiety as potential antioxidant, antimicrobial, and anticancer

Synthesis, Characterization, and Biological Evaluation of Gabapentinoid Hybrids with Isoindole-1,3(2H)-dione Moiety as Potential Antioxidant, Antimicrobial, and Anticancer Agents

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