Novel benzochromenes: design, synthesis, cytotoxicity, molecular docking and mechanistic investigations DOI
Fatma G. Abdulrahman, Hamada S. Abulkhair,

Riham A. Zidan

et al.

Future Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 16(2), P. 105 - 123

Published: Jan. 1, 2024

Aim: A novel series of fused benzochromenes with expected cytotoxicity and HIF-1α inhibition was identified. Materials & methods: bioisosterism-aided approach applied to design new assess their against three cancer cell lines. The probable mechanistic effect the in silico docking pharmacokinetic profiles most effective derivatives were evaluated. Results: Compounds 3, 4, 5, 8 11 showed potent antiproliferative activity excellent selectivity. Compound significant an IC50 value 3.372 μM. It also enhanced apoptosis arrested HepG2 cycle at both G0/G1 S stages. Conclusion: identified as a potential anticancer candidate.

Language: Английский

Development of 1,2,3-triazole hybrids as multi-faced anticancer agents co-targeting EGFR/mTOR pathway and tubulin depolymerization DOI
Mennatallah A. Shaheen, Khaled M. Darwish, Safaa M. Kishk

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 156, P. 108153 - 108153

Published: Jan. 11, 2025

Language: Английский

Citations

2
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

et al.

RSC Advances, Journal Year: 2022, Volume and Issue: 12(41), P. 26895 - 26907

Published: Jan. 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.

Language: Английский

Citations

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

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(3), P. 463 - 463

Published: March 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.

Language: Английский

Citations

39
Quinazoline-based VEGFR-2 inhibitors as potential anti-angiogenic agents: A contemporary perspective of SAR and molecular docking studies DOI Creative Commons

Mahfam Moradi,

Ali Mousavi, Zahra Emamgholipour

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 259, P. 115626 - 115626

Published: July 8, 2023

Language: Английский

Citations

31
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

et al.

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 133, P. 106397 - 106397

Published: Feb. 1, 2023

Language: Английский

Citations

22
Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α -amylase, and α -glucosidase: synthesis, molecular docking, and ADMET studies DOI Creative Commons

Nirvana A. Gohar,

Eman A. Fayed, Yousry A. Ammar

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 39(1)

Published: June 24, 2024

Inhibition of α-glucosidase and α-amylase are key tactics for managing blood glucose levels. Currently, stronger, more accessible inhibitors needed to treat diabetes. Indeno[1,2-b] quinoxalines-carrying thiazole hybrids 1–17 were created described using NMR. All analogues tested hypoglycaemic effect against STZ-induced diabetes in mice. Compounds 4, 6, 8, 16 the most potent among synthesised analogues. These examined their effects on plasma insulin, urea, creatinine, GSH, MDA, ALT, AST, total cholesterol. Moreover, these compounds enzymes vitro. The four represented moderate activity with IC50 values 0.982 ± 0.04, 10.19 0.21 inhibition 17.58 0.74 121.6 5.14 μM when compared standard medication acarbose IC50=0.316 0.02 31.56 1.33 inhibition. Docking studies as well silico ADMT done.

Language: Английский

Citations

12
Design, synthesis, and mechanistic insight of novel imidazolones as potential EGFR inhibitors and apoptosis inducers DOI
Fatma G. Abdulrahman, Hamada S. Abulkhair,

Hoda S. El Saeed

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 144, P. 107105 - 107105

Published: Jan. 8, 2024

Language: Английский

Citations

8
Recent Advances and Future Directions on Small Molecule VEGFR Inhibitors in Oncological Conditions DOI

Amandeep Thakur,

Mandeep Rana,

Anshul Mishra

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 272, P. 116472 - 116472

Published: May 6, 2024

Language: Английский

Citations

8
The anticancer and EGFR-TK/CDK-9 dual inhibitory potentials of new synthetic pyranopyrazole and pyrazolone derivatives: X-ray crystallography, in vitro , and in silico mechanistic investigations DOI
Arafa Musa, Saleh Ihmaid, David L. Hughes

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 41(21), P. 12411 - 12425

Published: Jan. 20, 2023

Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to lack effective targeted medications, often resulting in recurrence metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9) overexpression correlates with worse overall survival patients. Pyranopyrazole pyrazolone privileged development anticancer agents. Inspired by this proven scientific fact, we report here synthesis two new series suggested molecules incorporating both heterocycles together their characterization IR, 1H NMR, 13C NMR-DEPT, X-ray diffraction methods. An attempt get pyranopyrazole-gold complexes was conducted but unexpectedly yielded benzylidene-2,4-dihydro-3H-pyrazol-3-one instead. unexpected result confirmed crystallographic analysis. All newly synthesized compounds were assessed anti-proliferative activity against different human cells, obtained results compared reference drug Staurosporine. The target revealed variable cytotoxicity IC50 at a low micromolar range superior selectivity indices. Target enzyme EGFR-TK CDK-9 assays showed 22 23 effectively inhibited biological targets values 0.143 0.121 µM, respectively. Molecular docking experiments molecular dynamics simulation also further rationalize vitro results.Communicated Ramaswamy H. Sarma.

Language: Английский

Citations

21
A novel class of phenylpyrazolone-sulphonamides rigid synthetic anticancer molecules selectively inhibit the isoform IX of carbonic anhydrases guided by molecular docking and orbital analyses DOI
Maan T. Khayat, Hany E. A. Ahmed, Abdelsattar M. Omar

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 41(24), P. 15243 - 15261

Published: March 13, 2023

All the previously reported phenylpyrazoles as carbonic anhydrase inhibitors (CAIs) were found to have small sizes and high levels of flexibility, hence showed low selectivity profiles toward a particular isoform CA. Herein, we report development more rigid ring system bearing sulfonamide hydrophilic head lipophilic tail develop novel molecules that are suggested better special CA isoform. Accordingly, three sets pyrano[2,3-c]pyrazoles attached with aryl hydrophobic synthesized enhance specific human anhydrases (hCAs). The impact both attachments on potency has been extensively discussed in terms vitro cytotoxicity evaluation under hypoxic conditions, structure-activity relationship enzyme assay. new candidates displayed good cytotoxic activities against breast colorectal carcinomas. Results assay demonstrated preferential compounds 22, 24 27 inhibit IX hCAs selectively. Wound-healing also performed revealed potential decrease wound closure percentage MCF-7 cells. Molecular docking molecular orbital analysis finally conducted. indicate binding interactions several crucial amino acids hCA IX.Communicated by Ramaswamy H. Sarma.

Language: Английский

Citations

17