Identification of Potential Inhibitors of TGFβR1 for the treatment of Cancer through Structure‐based virtual screening and Molecular dynamics simulations DOI
Saumya Rastogi, Shashank Shekher Mishra, Lakhveer Singh

et al.

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Abstract Globally, cancer is one of the leading causes death. Resistance to conventional medications, such as chemotherapy and radiation, continues be a significant challenge in treatment despite availability numerous medicines. Therefore, highest priority hunt for new therapeutic agents. Transforming growth factor‐beta pivotal regulatory cytokine that exerts influence over cellular processes, particularly emphasizing its role facilitating modulating cell proliferation. TGF‐β receptor 1, identified most promising active site signaling, potent drug target has garnered wide attention developing anticancer The present investigation investigates potential natural products TGFβR1 inhibitors. SB431542 complexed protein model was used screen product database obtain compound with high binding potential. NPC247629 emerged best‐scored among all screened compounds, demonstrating affinity towards regarding docking score −17.54 kcal/mol. all‐atoms MD simulation study indicated proposed hits are retained inside dynamic states. Additionally, principal component free energy landscape analysis were performed explore mechanism top‐hit products. best‐screened hits, NPC60735, have excellent hold massive inhibition, paving way future investigations treatment.

Language: Английский

Design and synthesis of new nicotinamides as immunomodulatory VEGFR-2 inhibitors and apoptosis inducers DOI
Reda G. Yousef, Ibrahim H. Eissa, Hazem Elkady

et al.

Future Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 16(24), P. 2583 - 2598

Published: Nov. 14, 2024

Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery.

Language: Английский

Citations

1
Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR WT , EGFR T790M , and EGFR L858R ) DOI Creative Commons

Mahmoud G. Abo Al-Hamd,

Haytham O. Tawfik, Omeima Abdullah

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 38(1)

Published: Aug. 7, 2023

Hexahydroquinoline (HHQ) scaffold was constructed and recruited for development of new series anticancer agents. Thirty-two compounds were synthesised where x-ray crystallography performed to confirm enantiomerism. Thirteen showed moderate good activity against NCI 60 cancer cell lines, with GI % mean up 74%

Language: Английский

Citations

3
Computer-Assisted Drug Discovery of a Novel Theobromine Derivative as an EGFR Protein-Targeted Apoptosis Inducer DOI Creative Commons
Ibrahim H. Eissa, Reda G. Yousef, Eslam B. Elkaeed

et al.

Evolutionary Bioinformatics, Journal Year: 2023, Volume and Issue: 19

Published: Jan. 1, 2023

The overexpression of the Epidermal Growth Factor Receptor (EGFR) marks it as a pivotal target in cancer treatment, with aim reducing its proliferation and inducing apoptosis. This study aimed at CADD new apoptotic EGFR inhibitor. natural alkaloid, theobromine, was used starting point to obtain semisynthetic (di-ortho-chloro acetamide) derivative (T-1-DOCA). Firstly, T-1-DOCA’s total electron density, energy gap, reactivity indices, electrostatic surface potential were determined by DFT calculations, Then, molecular docking studies carried out predict T-1-DOCA against wild mutant proteins. correct binding further confirmed dynamics (MD) over 100 ns, MM-GPSA, PLIP experiments. In vitro, showed noticeable efficacy compared erlotinib suppressing WT T790M IC 50 values 56.94 269.01 nM, respectively. inhibited also H1975 HCT-116 malignant cell lines, exhibiting 14.12 23.39 µM, selectivity indices 6.8 4.1, respectively, indicating anticancer general safety. effects indicated flow cytometric analysis through increase levels BAX, Casp3, Casp9, decrease Bcl-2 levels. conclusion, T-1-DOCA, inhibitor, designed evaluated both computationally experimentally. results suggest that is promising candidate for development an anti-cancer drug.

Language: Английский

Citations

3
A new anticancer derivative of the natural alkaloid, theobromine, as an EGFR inhibitor and apoptosis inducer DOI
Ibrahim H. Eissa, Reda G. Yousef, Hazem Elkady

et al.

Theoretical Chemistry Accounts, Journal Year: 2023, Volume and Issue: 143(1)

Published: Dec. 4, 2023

Language: Английский

Citations

2
Integration of 3D-QSAR, Molecular Docking, and Machine Learning Techniques for Rational Design of Nicotinamide-Based SIRT2 Inhibitors DOI
Aleksandra Ilić, Nemanja Djoković, Teodora Djikić

et al.

Computational Biology and Chemistry, Journal Year: 2024, Volume and Issue: 113, P. 108242 - 108242

Published: Oct. 11, 2024

Language: Английский

Citations

0
Identification of Potential Inhibitors of TGFβR1 for the treatment of Cancer through Structure‐based virtual screening and Molecular dynamics simulations DOI
Saumya Rastogi, Shashank Shekher Mishra, Lakhveer Singh

et al.

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Abstract Globally, cancer is one of the leading causes death. Resistance to conventional medications, such as chemotherapy and radiation, continues be a significant challenge in treatment despite availability numerous medicines. Therefore, highest priority hunt for new therapeutic agents. Transforming growth factor‐beta pivotal regulatory cytokine that exerts influence over cellular processes, particularly emphasizing its role facilitating modulating cell proliferation. TGF‐β receptor 1, identified most promising active site signaling, potent drug target has garnered wide attention developing anticancer The present investigation investigates potential natural products TGFβR1 inhibitors. SB431542 complexed protein model was used screen product database obtain compound with high binding potential. NPC247629 emerged best‐scored among all screened compounds, demonstrating affinity towards regarding docking score −17.54 kcal/mol. all‐atoms MD simulation study indicated proposed hits are retained inside dynamic states. Additionally, principal component free energy landscape analysis were performed explore mechanism top‐hit products. best‐screened hits, NPC60735, have excellent hold massive inhibition, paving way future investigations treatment.

Language: Английский

Citations

0