Rational Design Problematics of Peptide Nucleic Acids as SARS-CoV-2 Inhibitors DOI Creative Commons
Tatyana A. Grigoreva, Светлана В. Ворона, Daria Novikova

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

The use of viral protein inhibitors has shown to be insufficiently effective in the case highly variable SARS-CoV-2. In this work, we examined possibility designing agents that bind a conserved region coronavirus (+)RNA. We demonstrated while design antisense RNAs is based on complementary interaction nitrogenous bases, it possible semirigid docking methods unnatural peptide nucleic acids. transition from N-(2-aminoethyl)glycine chain more conformationally rigid piperidine-containing backbone allowed us significantly increase affinity structures target RNA.

Language: Английский

Lead Optimization of BIBR1591 To Improve Its Telomerase Inhibitory Activity: Design and Synthesis of Novel Four Chemical Series with In Silico, In Vitro, and In Vivo Preclinical Assessments DOI
Ahmed A. Al‐Karmalawy, Mai H. A. Mousa, Marwa Sharaky

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 67(1), P. 492 - 512

Published: Dec. 20, 2023

Herein, modifications to the previously reported BIBR1591 were conducted obtain bioisosteric candidates with improved activities. The % inhibition of newly afforded against telomerase target was investigated. Notably, 6f achieved superior (63.14%) compared BIBR1532 and (69.64 51.58%, respectively). In addition, 8a 8b showed comparable promising 58.65 55.57%, respectively, which recorded be frontier that BIBR1591. 6f, 8a, tested five cancer cell lines related lung liver subtypes. Moreover, examined on both cycle progression apoptosis induction in HuH7 cells. Furthermore, vivo antitumor activity further assessed female mice solid Ehrlich carcinoma. molecular docking dynamics simulations carried out. Collectively, could considered potential new inhibitors subjected investigation and/or optimization.

Language: Английский

Citations

14
Multi-target rational design and synthesis of novel diphenyl-tethered pyrazolopyrimidines targeting EGFR and topoisomerase II with potential DNA intercalation and apoptosis induction DOI

Ahmed A. Abdel Gaber,

Ayman Abo Elmaaty, Marwa Sharaky

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 145, P. 107223 - 107223

Published: Feb. 17, 2024

Language: Английский

Citations

5
Metabolites profiling, in-vitro and molecular docking studies of five legume seeds for Alzheimer’s disease DOI Creative Commons
Rana M. Ibrahim, Passent M. Abdel-Baki, Osama G. Mohamed

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 23, 2024

Abstract Even though legumes are valuable medicinal plants with edible seeds that extensively consumed worldwide, there is little information available on the metabolic variations between different dietary beans and their influence as potential anti-cholinesterase agents. High-resolution liquid chromatography coupled mass spectrometry in positive negative ionization modes combined multivariate analysis were used to explore differences profiles of five commonly seeds, fava bean, black-eyed pea, kidney red lentil, chickpea. A total 139 metabolites from various classes identified including saponins, alkaloids, phenolic acids, iridoids, terpenes. Chickpea showed highest antioxidant effects, followed by beans. Supervised unsupervised chemometric determined species could be distinguished discriminatory metabolites. The major pathways also studied. Glycerophospholipid metabolism was most significantly enriched KEGG pathway. Pearson’s correlation pinpointed 18 positively correlated activity. Molecular docking biomarkers active sites acetyl- butyryl-cholinesterase enzymes revealed promising binding scores, validating results. present study will add metabolomic nutritional value advocate inclusion anti-Alzheimer’s formulations.

Language: Английский

Citations

5
Design and synthesis of new 1,2,3-triazole derivatives as VEGFR-2/telomerase downregulatory candidates endowed with apoptotic potential for cancer treatment DOI
Ahmed A. Al‐Karmalawy,

Mohamed A. Zeidan,

Ayman Abo Elmaaty

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 156, P. 108159 - 108159

Published: Jan. 11, 2025

Language: Английский

Citations

0
TiO2 Nanoparticles Catalyzed Synthesis, Pharmacological Evaluation, and Molecular Docking Studies of New Pyrido[2,3-d]Pyrimidine Derivatives as CDK1 Inhibitors DOI

Eman Abd Alsalam,

Hanem M. Awad, Eslam M. Abbass

et al.

Chemistry Africa, Journal Year: 2025, Volume and Issue: unknown

Published: March 9, 2025

Language: Английский

Citations

0
Experimental design of D-α-tocopherol polyethylene glycol 1000 succinate stabilized bile salt based Nano-vesicles for improved cytotoxicity and bioavailability of colchicine binding site inhibitor Candidates: In Vitro, in silico, and pharmacokinetic studies DOI
Ayman Abo Elmaaty, Ahmed A. Al‐Karmalawy, Mohamed S. Nafie

et al.

International Journal of Pharmaceutics, Journal Year: 2023, Volume and Issue: 640, P. 122980 - 122980

Published: April 27, 2023

Language: Английский

Citations

8
Design and Synthesis of Novel Pyrazolopyrimidine Candidates As Promising EGFR-T790M Inhibitors and Apoptosis Inducers DOI

Ahmed A. Abdel Gaber,

Marwa Sharaky, Ayman Abo Elmaaty

et al.

Future Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 15(19), P. 1773 - 1790

Published: Oct. 1, 2023

Aim: Our objective was to design and synthesize a new range of pyrazolopyrimidines while maintaining the key pharmacophoric features EGFR tyrosine kinase inhibitors. Materials & methods: Percentage inhibition in 14 human cancer cell lines IC50 values were recorded. Compounds 6c, 7e 7f examined against both wild mutant (T790M) subtypes. Apoptosis markers, cycle arrest, apoptosis assay molecular docking performed. Results: demonstrated superior inhibitory potentials A study showed that compounds 6c had best fit. Conclusion: The designed candidates potential as promising EGFR-T790M inhibitors agrees with proposed rationale.

Language: Английский

Citations

7
Design and synthesis of novel tetrabromophthalimide derivatives as potential tubulin inhibitors endowed with apoptotic induction for cancer treatment DOI

Marwa Abdel‐Motaal,

Dalal Ali Aldakhili,

Ayman Abo Elmaaty

et al.

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(4)

Published: May 15, 2024

Abstract Although various approaches exist for treating cancer, chemotherapy continues to hold a prominent role in the management of this disease. Besides, microtubules serve as vital component cellular skeleton, playing pivotal process cell division making it an attractive target cancer treatment. Hence, scope work was adapted design and synthesize new anti‐tubulin tetrabromophthalimide hybrids ( 3 ‐ 17 ) with colchicine binding site (CBS) inhibitory potential. The conducted vitro studies showed that compound 16 displayed lowest IC 50 values (11.46 µM) at FaDu lines, whereas exhibited value (13.62 PC3 line. However, 7b (11.45 MDA‐MB‐468 Moreover, observed be superior antitumor candidate against all three tested lines (MDA‐MB‐468, PC3, FaDu) 17.22, 13.15, 13.62 µM, respectively. In addition, well‐established upregulation apoptotic markers (Caspases 3, 7, 8, 9, Bax, P53). induced downregulation antiapoptotic (MMP2, MMP9, BCL‐2). Furthermore, inhibition assay compounds 15a particularly significant potentials, 23.07 4.25 respectively, compared colchicine, which had 3.89 µM. Additionally, cycle analysis conducted, showing could prompt arrest both G0‐G1 G2‐M phases. On other hand, molecular docking approach applied investigate interactions examined candidates towards CBS β‐tubulin subunit. Thus, synthesized can regarded outstanding anticancer activity.

Language: Английский

Citations

2
Investigating the Potential Anti-SARS-CoV-2 and Anti-MERS-CoV Activities of Yellow Necklacepod among Three Selected Medicinal Plants: Extraction, Isolation, Identification, In Vitro, Modes of Action, and Molecular Docking Studies DOI Creative Commons
Howaida I. Abd‐Alla, Omnia Kutkat, Heba-tollah M. Sweelam

et al.

Metabolites, Journal Year: 2022, Volume and Issue: 12(11), P. 1109 - 1109

Published: Nov. 13, 2022

The anti-MERS-CoV activities of three medicinal plants (Azadirachta indica, Artemisia judaica, and Sophora tomentosa) were evaluated. highest viral inhibition percentage (96%) was recorded for S. tomentosa. Moreover, the mode action both tomentosa A. judaica showed 99.5% 92% inhibition, respectively, with virucidal as main action. Furthermore, anti-SARS-CoV-2 measured. Notably, activity very high (100%) slightly lower (96%). Therefore, phytochemical investigation promising L. led to isolation structural identification nine compounds (1−9). Then, CC50 IC50 values isolated against SARS-CoV-2 Compound 4 (genistein 4’-methyl ether) achieved superior an value 2.13 µm. Interestingly, that adsorption mechanisms effective. Additionally, MERS-CoV found be 1.01 3.11 µg/mL, respectively. In addition, all subjected two separate molecular docking studies spike (S) protease (Mpr°) receptors SARS-CoV-2.

Language: Английский

Citations

12
Computational Design, Synthesis, and Biophysical Evaluation of β-Amido Boronic Acids as SARS-CoV-2 Mpro Inhibitors DOI Creative Commons
Enrico Mario Alessandro Fassi, Marco Manenti, Andrea Citarella

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(5), P. 2356 - 2356

Published: March 3, 2023

The COVID-19 pandemic has given a strong impetus to the search for antivirals active on SARS-associated coronaviruses. Over these years, numerous vaccines have been developed and many of are effective clinically available. Similarly, small molecules monoclonal antibodies also approved by FDA EMA treatment SARS-CoV-2 infection in patients who could develop severe form COVID-19. Among available therapeutic tools, molecule nirmatrelvir was 2021. It is drug capable binding Mpro protease, an enzyme encoded viral genome essential intracellular replication. In this work, virtual screening focused library β-amido boronic acids, we designed synthesized compounds. All them were biophysically tested microscale thermophoresis, attaining encouraging results. Moreover, they displayed protease inhibitory activity, as demonstrated performing enzymatic assays. We confident that study will pave way design new drugs potentially useful infection.

Language: Английский

Citations

6