Triad pyrazole–thiazole–coumarin heterocyclic core effectively inhibit HSP and drive cancer cells to apoptosis DOI
Mehmet Gümüş, İrfan Koca, Yusuf Sert

и другие.

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер 41(23), С. 14382 - 14397

Опубликована: Фев. 24, 2023

Intensive studies on hepatocellular carcinoma (HCC), which is spreading rapidly around the world and has a high mortality rate, due to lack of adequate preventive or curative treatment methods. Treating patients with HCC become very challenging because heterogeneity in patient population lead activation different signaling pathways, pathway crosstalk for patients. Therefore, understanding these molecular mechanisms combining drugs therapies overcome drawbacks an area utmost importance. In this study, biological activities designed characterized triad Pyrazole-Thiazol-Coumarin (PTC) compounds were determined by performing cell viability, qPCR array, apoptosis cycle assays. One (PTC10) implicitly suppresses multiple pathways (RAS/MAP kinase PI3K-AKT) simultaneously. This action provided (i) arresting cancer cells at G2 phase, (ii) driving (iii) inhibiting HSP network. Remarkably, apoptotic factor help survive. HSP90 also coordinates Cdk4/Cdc37, therefore both drives arrest apoptosis. ATP hydrolysis aggregation assay further displayed specific inhibition. PTC provides unique drug template treatment.

Язык: Английский

Hydrazide-hydrazone/hydrazone as enabling linkers in anti-cancer drug discovery: A comprehensive review DOI

Solai Murugappan,

Sowmya Dastari,

Kalyani Jungare

и другие.

Journal of Molecular Structure, Год журнала: 2024, Номер 1307, С. 138012 - 138012

Опубликована: Март 11, 2024

Язык: Английский

Процитировано

23
Schiff bases and their metal complexes to target and overcome (multidrug) resistance in cancer DOI
Ana Podolski-Renić, Ana Čipak Gašparović, Andreia Valente

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 270, С. 116363 - 116363

Опубликована: Март 29, 2024

Язык: Английский

Процитировано

23
From triazolophthalazines to triazoloquinazolines: A bioisosterism-guided approach toward the identification of novel PCAF inhibitors with potential anticancer activity DOI
Mohamed H. El‐Shershaby,

Adel Ghiaty,

Ashraf H. Bayoumi

и другие.

Bioorganic & Medicinal Chemistry, Год журнала: 2021, Номер 42, С. 116266 - 116266

Опубликована: Июнь 5, 2021

Язык: Английский

Процитировано

65
Pharmacophore‐linked pyrazolo[3,4‐d]pyrimidines as EGFR‐TK inhibitors: Synthesis, anticancer evaluation, pharmacokinetics, and in silico mechanistic studies DOI

Ahmed A. Abdel Gaber,

Ahmed El‐Morsy,

Farag F. Sherbiny

и другие.

Archiv der Pharmazie, Год журнала: 2021, Номер unknown

Опубликована: Авг. 31, 2021

Abstract Targeting the epidermal growth factor receptors (EGFRs) with small inhibitor molecules has been validated as a potential therapeutic strategy in cancer therapy. Pyrazolo[3,4‐ d ]pyrimidine is versatile scaffold that exploited for developing anticancer agents. On basis of fragment‐based drug discovery, considering essential pharmacophoric features potent EGFR tyrosine kinase (TK) inhibitors, herein, we report design and synthesis new hybrid pyrazolo[3,4‐ linked diverse fragments reported potential. These include hydrazone, indoline‐2‐one, phthalimide, thiourea, oxadiazole, pyrazole, dihydropyrazole. The synthesized were evaluated their activity against human breast cell line, MCF‐7. obtained results revealed comparable antitumor reference drugs doxorubicin toceranib. Docking studies performed along EGFR‐TK ADMET profiling studies. docking showed ability designed compounds to interact key residues through number covalent noncovalent interactions. compound 25 (IC 50 = 2.89 µM) suggested it may serve lead further optimization development.

Язык: Английский

Процитировано

58
The antimicrobial potential and pharmacokinetic profiles of novel quinoline-based scaffolds: synthesis and in silico mechanistic studies as dual DNA gyrase and DHFR inhibitors DOI
Mohamed H. El‐Shershaby, Kamal M. El‐Gamal, Ashraf H. Bayoumi

и другие.

New Journal of Chemistry, Год журнала: 2021, Номер 45(31), С. 13986 - 14004

Опубликована: Янв. 1, 2021

The resistance of pathogenic microbes to currently available antimicrobial agents has been considered a global alarming concern.

Язык: Английский

Процитировано

57
Apoptosis induction, PARP-1 inhibition, and cell cycle analysis of leukemia cancer cells treated with novel synthetic 1,2,3-triazole-chalcone conjugates DOI

Esraa M. Othman,

Eman A. Fayed, Ebtehal M. Husseiny

и другие.

Bioorganic Chemistry, Год журнала: 2022, Номер 123, С. 105762 - 105762

Опубликована: Март 26, 2022

Язык: Английский

Процитировано

55
In vitroand computational investigations of novel synthetic carboxamide-linked pyridopyrrolopyrimidines with potent activity as SARS-CoV-2-MProinhibitors DOI Creative Commons
Ateyatallah Aljuhani, Hany E. A. Ahmed, Saleh Ihmaid

и другие.

RSC Advances, Год журнала: 2022, Номер 12(41), С. 26895 - 26907

Опубликована: Янв. 1, 2022

An essential target for COVID-19 is the main protease of SARS-CoV-2 (Mpro). With objective targeting this receptor, a novel set pyrido[1,2-a]pyrrolo[2,3-d]pyrimidines with terminal carboxamide fragments was designed, synthesized, and considered as an initial motif creation effective pan-coronavirus inhibitors. Accordingly, nine derivatives (21-29) have been introduced in vitro assay to evaluate their antiviral activity cytotoxicity effect against virus using Vero cells. The obtained data revealed that majority these showed potent cellular anti-COVID-19 prevent viral growth by more than 90% at two different concentrations weak or even no detectable cytotoxic on Extensive molecular docking simulations highlighted proper non-covalent interaction new compounds within binding pocket Mpro potential activity. In all synthesized indicated 25 29 promising inhibitory IC50 values low micromolar concentrations. dynamic simulation results predicted stability compound cavity hence supported high shown assay. These suggested merit further investigations drug candidates management SARS-CoV-2.

Язык: Английский

Процитировано

41
Phenylpyrazolone-1,2,3-triazole Hybrids as Potent Antiviral Agents with Promising SARS-CoV-2 Main Protease Inhibition Potential DOI Creative Commons
Arafa Musa, Hamada S. Abulkhair, Ateyatallah Aljuhani

и другие.

Pharmaceuticals, Год журнала: 2023, Номер 16(3), С. 463 - 463

Опубликована: Март 20, 2023

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

Язык: Английский

Процитировано

39
Exploring the cytotoxic effect and CDK-9 inhibition potential of novel sulfaguanidine-based azopyrazolidine-3,5-diones and 3,5-diaminoazopyrazoles DOI
Ebtehal M. Husseiny, Hamada S. Abulkhair,

Nehad M. El‐Dydamony

и другие.

Bioorganic Chemistry, Год журнала: 2023, Номер 133, С. 106397 - 106397

Опубликована: Фев. 1, 2023

Язык: Английский

Процитировано

22
Phthalazine‐based VEGFR‐2 inhibitors: Rationale, design, synthesis, in silico, ADMET profile, docking, and anticancer evaluations DOI

Fathalla Khedr,

Mohamed‐Kamal Ibrahim,

Ibrahim H. Eissa

и другие.

Archiv der Pharmazie, Год журнала: 2021, Номер 354(11)

Опубликована: Авг. 19, 2021

In the designed compounds, a new linker was inserted in form of fragments with verified VEGFR-2 inhibitory potential, including an α,β-unsaturated ketonic fragment, pyrazole, and pyrimidine. Also, distal hydrophobic moieties were attached to these linkers that are expected increase interaction and, consequently, affinity. These structural optimizations have led us identify novel dihydropyrazole derivative 6e as promising hit molecule. All derivatives evaluated assess their anticancer activity against three human cancer cell lines, HepG2, HCT-116, MCF-7. The results vitro evaluation study revealed moderate excellent cytotoxicity 6c , 6g 7b IC50 values low micromolar range. investigated for 16 compounds. enzyme assay compounds compared those sorafenib reference inhibitor. obtained demonstrated our potent inhibitors. most showed range 0.11-0.22 µM. Molecular docking pharmacokinetic studies also conducted rationalize evaluate ability be developed good drug candidates.

Язык: Английский

Процитировано

49