A structure-based approach to explore novel COX-2 inhibitors using pharmacophore modelling, 3D-QSAR analysis, virtual screening and dynamics simulation study

Krishnendu, Prayaga Rajappan; Benny, Sonu; Kumar, Sunil; Jayan, Jayalakshmi; Bhaskar, Vaishnav; Pappachen, Leena.K.; Aneesh, T P; Abdelgawad, Mohamed A.; Ghoneim, Mohammed M.; Nicolotti, Orazio; Zachariah, Subin Mary; Mathew, Bijo

doi:10.1016/j.molstruc.2023.136634

Cited by 8 publications

(2 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The e-pharmacophore hypothesis, created for the active region of the 4ASD crystal structure, consists of five pharmacophores. The five pharmacophores presented in Figure include two aromatic rings (R7 and R8), one hydrogen bond donor (D4), one hydrogen bond acceptor (A3), and one hydrophobic (H6) interaction. , …”

Section: Results and Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Investigation of Newly Synthesized Fluorinated Isatin-Hydrazones by In Vitro Antiproliferative Activity, Molecular Docking, ADME Analysis, and e-Pharmacophore Modeling

Başaran,

Köprü,

Akkoç

et al. 2024

ACS Omega

View full text Add to dashboard Cite

In this study, we investigated the in vitro antiproliferative activities and performed computational studies of newly synthesized fluorinated isatin-hydrazones. The chemical structures of the synthesized compounds were confirmed by FT-IR, 1D NMR ( 1 H-and 13 C NMR and APT), 2D NMR (HETCOR and HMBC), and elemental analysis. All compounds (1−15) were tested in human lung (A549) and liver (HepG2) cancer cell lines for 72 h. The compounds were screened against a healthy embryonic kidney cell line (HEK-293T) under the same conditions to determine their toxic effects. According to the results obtained, one of the compounds, in particular, compound 8 was effective at inhibiting the growth of cancerous cells, and its effects on both cancer cell lines were similar to IC 50 values of 42.43 and 48.43 μM for A549 and HepG2, respectively. Compound 8, which was determined to be the best anticancer agent in vitro, was chosen to interact with the target via molecular docking. This selected ligand (compound 8) interacted with the targets 4HJO, 4ASD, 3POZ, and 7TZ7, and docked into the active sites. The docking score, Glide energy, and Glide emodel values were calculated and determined to be lower than those of the reference compound cisplatin. The pharmacokinetic properties, stability, and drug-likeness parameters of all designed compounds were estimated using SwissADME. Finally, the binding affinities of compound 8 for all four targets were calculated using the MM-GBSA method.

show abstract

Section: Results and Discussionmentioning

confidence: 99%

“…The five pharmacophores presented in Figure 9 include two aromatic rings (R7 and R8), one hydrogen bond donor (D4), one hydrogen bond acceptor (A3), and one hydrophobic (H6) interaction. 47 , 48 …”

Section: Results and Discussionmentioning

confidence: 99%

Investigation of Newly Synthesized Fluorinated Isatin-Hydrazones by In Vitro Antiproliferative Activity, Molecular Docking, ADME Analysis, and e-Pharmacophore Modeling

Başaran,

Köprü,

Akkoç

et al. 2024

ACS Omega

View full text Add to dashboard Cite

show abstract

Computer‐assisted Methods and Tools for Structure‐ and Ligand‐based Drug Design

Mishra,

Roy,

Chhetri

et al. 2024

Computational Methods for Rational Drug Design

View full text Add to dashboard Cite

Synthesis of Sulfonamide‐Based Schiff Bases as Potent Anticancer Agents: Spectral Analyses, Biological Activity, Molecular Docking, ADME, DFT, and Pharmacophore Modelling Studies

Başaran,

Çakmak,

Türkmenoğlu

et al. 2024

Chemistry & Biodiversity

View full text Add to dashboard Cite

The current study focuses on the synthesis and characterization of six benzenesulfonamide‐based Schiff base derivatives (7–12) with various electron‐withdrawing and electron‐donating substituents (‐F, ‐CI, ‐Br, ‐CH3, and ‐OCH3) and the assessment of their antiproliferative activities against human lung (A549) and liver (HepG2) cancer cell lines using in vitro and in silico approaches. The structures of the synthesized compounds (7–12) were elucidated by elemental analysis and FT‐IR, 1D (1H, 13C, APT, and DEPT‐135), and 2D (HMQC and HMBC) NMR spectroscopies. The cytotoxic activities of the targeted compounds were determined at various concentrations against these cancer cell lines for 72 h, using the MTT method. The targeted molecules (7–12) demonstrated remarkable antiproliferative activities, with IC50 values ranging from 6.032–9.533 μM against the A549 cell line and 5.244–9.629 μM against the HepG2 cell line. These compounds showed activities at lower or very similar concentrations to cisplatin against the A549 cell line and at much lower concentrations than cisplatin against the HepG2 cell line. Among them, compounds 10 and 12 were found to be more effective against A549 and HepG2 cells, respectively, than cisplatin. These compounds were analyzed by interacting with the 1BNA, 4HJO, and 4ASD crystal structures in molecular docking studies.

show abstract

A structure-based approach to explore novel COX-2 inhibitors using pharmacophore modelling, 3D-QSAR analysis, virtual screening and dynamics simulation study

Cited by 8 publications

References 54 publications

Investigation of Newly Synthesized Fluorinated Isatin-Hydrazones by In Vitro Antiproliferative Activity, Molecular Docking, ADME Analysis, and e-Pharmacophore Modeling

Investigation of Newly Synthesized Fluorinated Isatin-Hydrazones by In Vitro Antiproliferative Activity, Molecular Docking, ADME Analysis, and e-Pharmacophore Modeling

Computer‐assisted Methods and Tools for Structure‐ and Ligand‐based Drug Design

Synthesis of Sulfonamide‐Based Schiff Bases as Potent Anticancer Agents: Spectral Analyses, Biological Activity, Molecular Docking, ADME, DFT, and Pharmacophore Modelling Studies

Contact Info

Product

Resources

About