Steroid‐Hymecromone Conjugates with Improved Antiproliferative and Antimicrobial Potential: Synthesis, Biological Evaluation, and in silico ADME Prediction DOI
Sevinç İlkar Erdağı

ChemistrySelect, Journal Year: 2023, Volume and Issue: 8(25)

Published: July 3, 2023

Abstract In this study, hymecromone with known therapeutic aspects was conjugated steroids a class of natural products that widely exhibited broad biological functions. Cholic acid, diosgenin, cholesterol, DHEA, and testosterone were selected as steroid moiety, each which has different mechanism action. This study focused on developing novel conjugates can be used multi‐targeted drugs for treating various diseases. All evaluated in vitro their antiproliferative antimicrobial activities discussed the structure‐activity relationship. The 5 6 comparable cytotoxic effects to reference against cancer cell lines (K562, MCF‐7, HeLa) while showing no toxicity healthy cells (L929). Conjugates 7 demonstrated antibacterial activity Gram‐positive Gram‐negative bacteria, lower minimum inhibitory concentration (MIC) values than standard ciprofloxacin drug. Conjugate , On other hand, had lowest MIC value fungus, drug ketoconazole. physicochemical pharmacokinetic properties silico computed evaluated. Overall, outputs suggest these have promising potential agents, offering approach treatment

Language: Английский

Assessment of the anti-cancer potential of Ephedra foeminea leaf extract on MDA-MB-231, MCF-7, 4 T1, and MCF-10 breast cancer cell lines: Cytotoxic, apoptotic and oxidative assays DOI Creative Commons

Samir Abdulkarim Alharbi,

Kamal Eldin Ahmed Abdelsalam, Mohammed Asad

et al.

Saudi Pharmaceutical Journal, Journal Year: 2024, Volume and Issue: 32(3), P. 101960 - 101960

Published: Jan. 20, 2024

Ephedra foeminea is traditionally used to treat breast cancer in several Arab countries. Scientific studies have reported different effects of this plant on some cell lines. The current study determined the anti-cancer potential methanolic extract against four types lines in-vitro. was prepared by maceration and phytoconstituents were identified LC-MS analysis. IC50 value MDA-MB-231, MCF-7, 4T1, MCF-10 using MTT assay. Further investigations carried out concentration (40.09 µg/ml) determine live/dead cells acridine orange/ethidium bromide staining. effect expression reactive oxygen species (ROS) evaluated flow cytometry. results analyzed one-way ANOVA followed Tukey's test. analysis revealed presence 34 30 positive negative modes respectively. most effective 4T1 a dose-dependent manner (P<0.001) with an 40.09 µg/ml showed negligible cells. It increased apoptosis 77.84% cells, as also ROS 39.57% that possesses increasing inducing result suggests foemenia reasonable due its oxidative pathways. confirm traditional belief cancer.

Language: Английский

Citations

4
Development of certain benzylidene coumarin derivatives as anti-prostate cancer agents targeting EGFR and PI3Kβ kinases DOI Creative Commons

Lina M. A. Abdel Ghany,

Tarek S. Ibrahim, Abdulrahman S. Alharbi

et al.

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

Published: Feb. 13, 2024

Novel coumarin derivatives were synthesised and tested for their cytotoxicity against human cancer cells (PC-3 MDA-MB-231). Compounds 5, 4b, 4a possessed potent cytotoxic activity PC-3 with IC50 3.56, 8.99, 10.22 µM, respectively. Compound 4c displayed more than erlotinib in the MDA-MB-231 8.5 µM. Moreover, compound 5 exhibited inhibitory on EFGR 0.1812 as well PI3Kβ that was twofold higher LY294002, suggesting this has a dual EGFR inhibiting activity. Docking aligns vitro results sheds light molecular mechanisms underlying targeting. Furthermore, decreased AKT m-TOR expression cells, showing it specifically targets these via EGFR/PI3K/Akt/m-TOR signalling pathway. Simultaneously, caused cell cycle arrest at S phase induced activation of both intrinsic extrinsic apoptotic pathways.

Language: Английский

Citations

4
Cassia fistula leaves extract profiling and its emphasis on induced ulcerative colitis in male rats through inhibition of caspase 3 and cyclooxygenase-2 DOI Creative Commons

Nada A. Abdellatif,

Enas E. Eltamany, Nahla S. El‐Shenawy

et al.

Arabian Journal of Chemistry, Journal Year: 2024, Volume and Issue: 17(4), P. 105672 - 105672

Published: Feb. 16, 2024

The objective of the study was to determine total phenolic and flavonoid contents (TPC TFC, respectively), as well solvent-partitioned fractions, leaf extract Cassia fistula. Using DPPH, TAC, FRAP tests, in vitro antioxidant properties crude its ethyl acetate fraction were investigated. Additionally, C. fistula chemical profiling accomplished using LC-ESI-MS/MS. Along with that, effectiveness (200 400 mg/kg) treating male rats ulcerative colitis (UC) induced by acetic acid assessed. According findings, had highest concentrations TPC (12.36 1.46 mg GAE/100 mg) TFC (5.12 0.64 QE/100 mg), impressive activity IC50 values DPPH (12.7 g/mL), (4.87 0.71 mM Fe+2/g), TAC (55. Fifty-five chemicals, predominantly phenolics (catechins, flavonoids, anthraquinones, chalcones, acids), detected LC/MS/MS. anti-UC effect dose-dependent. hematological parameters, liver biomarkers, oxidative stress, histopathology, immunohistochemistry revealed that prophylactic administration ameliorated all previous biomarkers. However, when administered on established colitis, it facilitated recovery inflamed mucosa showed better results than protection mode. phytoconstituents discovered here LC/MS/MS examined molecular docking studies for their binding affinities towards COX-2 caspase-3 proteins highlight anti-inflammatory antiapoptotic activities plant. Emodin compound displayed affinity proteins, while isorhamnetin have best associations essential amino acids caspase-3. Procyanidin B2 interestingly shows potent interactions important two targets. This has made possible utilize treatment UC clarified mechanism action.

Language: Английский

Citations

4
Playing Around the Coumarin Core in the Discovery of Multimodal Compounds Directed at Alzheimer’s-Related Targets: A Recent Literature Overview DOI Creative Commons
Mariagrazia Rullo, Gabriella La Spada, Angela Stefanachi

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 891 - 891

Published: Feb. 14, 2025

Alzheimer's disease (AD) causes a great socioeconomic burden because of its increasing prevalence and the lack effective therapies. The multifactorial nature AD prompts researchers to search for new strategies discovering disease-modifying therapeutics. To this extent, multitarget approach holds potential synergic or cooperative activities arising from compounds that are properly designed address two more pathogenetic mechanisms. As privileged nature-friendly scaffold, coumarin has successfully been enrolled as heterocyclic core in design multipotent anti-Alzheimer's agents. Herein, we comprehensively summarize most recent literature (2018-2023), covering rational discovery coumarin-containing directed ligands (MTDLs) whose anti-AD profile encompassed at least different biological relevant onset progression. enhance clarity presentation, synthetic coumarin-based MTDLs categorized into four clusters based on their substitution pattern reported bioactivities: (i) mono-, (ii) di-, (iii) polysubstituted coumarins protein targets, (iv) targets with additional metal-chelating features. Before discussing multimodal coumarins, rationale addressing each target is briefly presented.

Language: Английский

Citations

0
Harnessing the metastatic potential of human osteosarcoma cells by natural coumarin galbanic acid DOI
Abdolreza Ahmadi,

Fatemehsadat Hosseini,

Zahra Nasiri Sarvi

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Language: Английский

Citations

0
Diverse Mechanisms for the Aromatic Hydroxylation: Insights into the Mechanisms of the Coumarin Hydroxylation by CYP2A6 DOI Creative Commons
Zhixing Gan, Jianqiang Feng,

Jiabin Yin

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(21), P. 16277 - 16286

Published: Oct. 21, 2024

Different P450 isoforms may catalyze different types of reactions on the same substrate due to differences in their protein environments. To uncover how spatial environment within enzyme regulates reactivity, we conducted quantum mechanics/molecular mechanics (QM/MM) simulations CYP2A6-catalyzed 7-hydroxylation coumarin. The results revealed that water molecules can flexibly enter active site CYP2A6. In absence molecules, NIH shift mechanism was found be most favorable reaction pathway, leading keto intermediate further undergoes isomerization form C7-hydroxylated product. However, when are present at site, N-protonation route facilitated by waters and thus becomes preferred one. Both rationalize 1,2-H for aromatic hydroxylation reactions. This study highlights P450s employ diverse flexible mechanisms hydroxylation, offering deeper insight into P450-catalyzed

Language: Английский

Citations

3
A New Saponin (Zygo-albuside D) from Zygophyllum album Roots Triggers Apoptosis in Non-Small Cell Lung Carcinoma (A549 Cells) through CDK-2 Inhibition DOI Creative Commons
Enas E. Eltamany, Mohamed S. Nafie,

Dina M. Hal

et al.

ACS Omega, Journal Year: 2023, Volume and Issue: 8(33), P. 30630 - 30639

Published: Aug. 8, 2023

Phytochemical study of the ethyl acetate root extract Zygophyllum album has resulted in isolation a new saponin, Zygo-albuside D (1), along with two known compounds; (3-O-[β-D-quinovopyranosyl]-quinovic acid) (2), which is first reported root, and catechin (3), genus. Their chemical structures were established by NMR high-resolution mass spectrometry (HRMS). The saponin (1) exhibited promising cytotoxicity IC50 values 3.5 5.52 μM on A549 PC-3 cancer cell lines, respectively, compared to doxorubicin 9.44 11.39 respectively. While it had an value 46.8 against WISH cells. Investigating apoptosis-induction, compound 1 induced total apoptotic death lung cells 32-fold; 21.53% 0.67% untreated control Finally, upregulated pro-apoptotic genes downregulated antiapoptotic gene using expression levels. Compound remarkable CDK-2 target inhibition 96.2% 117.6 nM Roscovitine. molecular docking further confirmed binding affinity as CDK2 Bcl2 inhibitors that led apoptosis induction Hence, this highlights importance design anticancer agent specific mechanisms.

Language: Английский

Citations

6
In vitro anti-breast cancer study of hybrid cinnamic acid derivatives bearing 2-thiohydantoin moiety DOI
Dalal Nasser Binjawhar, Fawziah A. Al‐Salmi, Maha Al‐Ghamdi

et al.

Future Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 16(16), P. 1665 - 1684

Published: July 1, 2024

: To synthesize new hybrid cinnamic acids (

Language: Английский

Citations

1
Cornulacin: a new isoflavone from Cornulaca monacantha and its isolation, structure elucidation and cytotoxicity through EGFR-mediated apoptosis DOI
Ahmed M. Badawy, Enas E. Eltamany,

Rodina M. Hussien

et al.

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 15(9), P. 3228 - 3238

Published: Jan. 1, 2024

Cornulacin, a new isoflavone, was isolated from Cornulaca monacantha with structural elucidation and cytotoxicity against ovarian A2780 cancer through apoptosis induction.

Language: Английский

Citations

0
Thiazolidin-4-one derivatives as antitumor agents against (Caco-2) cell line: synthesis, characterization, in silico and in vitro studies DOI

Sara Olalla Saad,

Sahar S. El-Sakka,

Mohamed Helmy Abd El-hamied Soliman

et al.

Phosphorus, sulfur, and silicon and the related elements, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 14

Published: Oct. 24, 2024

Compounds based on thiazolidinones have drawn particular attention in the field of medicinal chemistry as potential sources novel drug-like molecules. In this study thiazolidin-4-one derivatives (3–17) were prepared by refluxing a mixture β-aroylacrylic acid (1) and aryl thiosemicarbazone (2) characterized using IR 1H NMR spectroscopy. silico, physicochemical descriptors pharmacokinetic properties assessed SwissADME web tool. Moreover, docking studies synthesized compounds performed order to explore their binding cyclooxygenase-2 (COX-2) (PDB code: 5IKT) p53 6MXZ). Some evaluated for vitro cytotoxic activity against colon cancer (Caco-2) cell line. Among tested compounds, compound (16) showed higher effect with (IC50 70 µg/ml). The revealed reduced Caspase-3 gene expression, suggesting antineoplastic effects these compounds.

Language: Английский

Citations

0