Exploring the Potential of Furofuran Lignans Isolated from Beilschmiedia pulverulenta for Drug Development: A Computational Approach DOI Creative Commons
Abubakar Siddiq Salihu, Wan Mohd Nuzul Hakimi Wan Salleh

Yüzüncü Yıl Üniversitesi Tarım Bilimleri Dergisi, Journal Year: 2023, Volume and Issue: 33(3), P. 491 - 502

Published: Sept. 11, 2023

Natural products have played a significant role in drug discovery and continue to be an important source of lead for new drugs. In recent years, computer-based methods emerged as effective approach identifying small molecule leads with desirable pharmacokinetic toxicity profiles. This study investigated the pharmacological bioactivity five furofuran lignans, namely, epiexcelsin, sesamin, sesartemin, syringaresinol, yangambin, isolated from plant Beilschmiedia pulverulenta. silico studies were conducted predict activities, toxicity, likeliness properties compounds. The results showed that all compounds had promising epiexcelsin exhibiting strong binding affinity (-8.13 kcal mol-1) inhibitory activity (1.1 µM) against estrogen receptor-α, predicted bioavailable lead. findings this provide insights into potential therapeutic uses natural medicinal plants emphasize combining traditional knowledge modern scientific approaches discovery. Overall, lignans pulverulenta represent development

Language: Английский

Novel promising benzoxazole/benzothiazole‐derived immunomodulatory agents: Design, synthesis, anticancer evaluation, and in silico ADMET analysis DOI
Hazem Elkady, Khaled El‐Adl,

Helmy Sakr

et al.

Archiv der Pharmazie, Journal Year: 2023, Volume and Issue: 356(9)

Published: June 28, 2023

Eleven novel benzoxazole/benzothiazole-based thalidomide analogs were designed and synthesized to obtain new effective antitumor immunomodulatory agents. The compounds evaluated for their cytotoxic activities against HepG-2, HCT-116, PC3, MCF-7 cells. Generally, the open with semicarbazide thiosemicarbazide moieties (10, 13a-c, 14, 17a,b) exhibited higher than derivatives closed glutarimide moiety (8a-d). In particular, compound 13a (IC50 = 6.14, 5.79, 10.26, 4.71 µM MCF-7, respectively) 14 7.93, 8.23, 12.37, 5.43 µM, highest anticancer four tested cell lines. most active further in vitro on tumor necrosis factor-alpha (TNF-α), caspase-8 (CASP8), vascular endothelial growth factor (VEGF), nuclear kappa-B p65 (NF-κB p65) HCT-116 Compounds showed a remarkable significant reduction TNF-α. Furthermore, they elevation CASP8 levels. Also, significantly inhibited VEGF. addition, decreases level of NF-κB while demonstrated an insignificant decrease respect thalidomide. Moreover, our good silico absorption, distribution, metabolism, elimination, toxicity (ADMET) profiles.

Language: Английский

Citations

20
Heterocyclic Compounds as Synthetic Tyrosinase Inhibitors: Recent Advances DOI Open Access
Serena Vittorio, Christian Dank, Laura Ielo

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 9097 - 9097

Published: May 22, 2023

Tyrosinase is a copper-containing enzyme which widely distributed in nature (e.g., bacteria, mammals, fungi) and involved two consecutive steps of melanin biosynthesis. In humans, an excessive production can determine hyperpigmentation disorders as well neurodegenerative processes Parkinson’s disease. The development molecules able to inhibit the high activity remain current topic medicinal chemistry, because inhibitors reported so far present several side effects. Heterocycle-bearing are largely diffuse this sense. Due their importance biologically active compounds, we decided report comprehensive review synthetic tyrosinase possessing heterocyclic moieties within last five years. For reader’s convenience, classified them mushroom (Agaricus bisporus) human tyrosinase.

Language: Английский

Citations

19
Design, synthesis, in silico studies, and biological evaluation of novel pyrimidine-5-carbonitrile derivatives as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers DOI Creative Commons
Abdulrahman M. Saleh,

Hazem A. Mahdy,

Mohamed Ayman El‐Zahabi

et al.

RSC Advances, Journal Year: 2023, Volume and Issue: 13(32), P. 22122 - 22147

Published: Jan. 1, 2023

A novel series of pyrimidine-5-carbonitrile derivatives bearing benzylidene and hydrazone moieties with different linkers (spacers) were designed synthesized as possible inhibitors the vascular endothelial growth factor receptor-2 (VEGFR-2). The newly compounds evaluated in vitro for their cytotoxic activities against two human cancer cell lines namely colon (HCT-116) breast (MCF-7) using sorafenib a standard anticancer drug. Compounds 9d, 11e, 12b, 12d showed higher than IC50 values ranging from 1.14 to 10.33 μM. In particular, compound 11e exhibited excellent HCT-116 MCF-7 1.54 μM, respectively. Moreover, about 47.32-fold activity normal fibroblast (WI-38) cells, lower cytotoxicity cells. 12b most potent VEGFR-2 0.61 0.53 respectively, compared sorafenib. Bedsides, arrested at S sub-G1 phases, induced significant increase apoptotic caused remarkable decrease levels TNF-α, IL-6, caspase-3. Finally, binding patterns target investigated through docking study proposed molecular (VEGFR-2, PDB ID 1YWN). results studies similar modes VEGFR-2. addition, dynamic simulations revealed stability active site 100 ns.

Language: Английский

Citations

19
Design, synthesis, anticancer evaluation, and in silico ADMET analysis of novel thalidomide analogs as promising immunomodulatory agents DOI Creative Commons

Anas Ramadan Kotb,

Abdallah E. Abdallah, Hazem Elkady

et al.

RSC Advances, Journal Year: 2023, Volume and Issue: 13(16), P. 10488 - 10502

Published: Jan. 1, 2023

Novel thalidomide analogs as anticancer immunomodulatory agents.

Language: Английский

Citations

12
Immunomodulation and anticancer evaluation of quinazoline-based thalidomide analogs: Design, synthesis, docking, and dynamic simulation DOI
Abdallah E. Abdallah, Ibrahim H. Eissa,

Ahmed B. M. Mehany

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1317, P. 139082 - 139082

Published: Dec. 1, 2024

Language: Английский

Citations

4
Novel triazoloquinazoline derivatives as VEGFR inhibitors: synthesis, cytotoxic evaluation and in silico studies DOI

Reda R. Mabrouk,

Hazem A. Mahdy,

Abdallah E. Abdallah

et al.

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13

Published: Feb. 25, 2025

New triazoloquinazoline derivatives were synthesized to explore their cytotoxic activity on various cancer cell lines, prompted by the need for effective anticancer agents. All compounds confirmed spectroscopic methods and tested in vitro inhibitory activities against hepatocellular carcinoma (HepG-2), breast (MCF-7), prostate (PC3) lines. Ten VEGFR-2. Additionally, studies investigated most active compound 6, including cycle analysis, apoptotic assessment, effect gene expression, safety profiling, molecular docking, MD simulation, ADMET analysis. Compounds 3a, 3c, 6 exhibited higher MCF-7 than doxorubicin. Compound was potent, arresting at G1 phase showing proapoptotic action. It significantly inhibited VEGFR-2 altered promoting BAX, P21, P53 while downregulating BCL-2. Docking simulations indicated stable interaction with VEGFR-2, safety, profiles suggested favorable drug-likeness safety. has shown promising potential, particularly cancer, but further research is needed confirm these findings address long-term

Language: Английский

Citations

0
A Review on Drug Discovery of Phthalimide Analogues as Emerging Pharmacophores: Synthesis and Biological Potential DOI
Manreet Kaur, Shivali Sharma, Divya Utreja

et al.

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(16)

Published: April 1, 2025

Abstract Phthalimide is a heterocyclic compound containing nitrogen atom and two carbonyl groups which form the basis for synthesis of various natural synthetic products that are employed in realms medicinal chemistry agrochemicals. It exploited purposes, drug modification as an agent against pests due to its versatile structure offers ease modifications effectiveness at molecular level biological systems. Incorporating phthalimide with other moieties such triazole, benzimidazole piperazine impart consequential structural prompting diversification repercussions living This review article seeks highlight recent achievements research based on compounds stemming from their followed by assessment potent antifungal, antibacterial, antitumor, antioxidant agents, discusses further potential.

Language: Английский

Citations

0
Targeting VEGFR-2 in breast cancer: synthesis and in silico and in vitro characterization of quinoxaline-based inhibitors DOI Creative Commons
Ibrahim H. Eissa, Alaa Elwan,

Mustafa A. Al-Qadhi

et al.

RSC Advances, Journal Year: 2025, Volume and Issue: 15(17), P. 12896 - 12916

Published: Jan. 1, 2025

Design, synthesis and in vitro silico studies of novel quinoxaline-based derivatives as antitumor VEGFR-2 inhibitors with apoptotic activities.

Language: Английский

Citations

0
Design, synthesis, anti-proliferative evaluation, docking, and MD simulation studies of new thieno[2,3-d]pyrimidines targeting VEGFR-2 DOI Creative Commons
Souad A. El‐Metwally, Hazem Elkady, Mohamed Hagras

et al.

RSC Advances, Journal Year: 2023, Volume and Issue: 13(33), P. 23365 - 23385

Published: Jan. 1, 2023

Design, synthesis, in vitro , and silico studies of new thieno[2,3- d ]pyrimidines as antitumor VEGFR-2 inhibitors with apoptotic activities.

Language: Английский

Citations

10
Design, Synthesis, and Biological Evaluation of Novel Quinazolin-4(3H)-one-Based Histone Deacetylase 6 (HDAC6) Inhibitors for Anticancer Activity DOI Open Access
Yogesh Mahadu Khetmalis, Ashna Fathima,

Markus Schweipert

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 11044 - 11044

Published: July 3, 2023

A series of novel quinazoline-4-(3H)-one derivatives were designed and synthesized as histone deacetylase 6 (HDAC6) inhibitors based on the cap group benzhydroxamic acid linker metal-binding group. total 19 analogues (5a-5s) obtained. The structures target compounds characterized using 1H-NMR, 13C-NMR, LC-MS, elemental analyses. Characterized screened for inhibition against HDAC8 class I, HDAC4 IIa, HDAC6 IIb. Among tested, 5b proved to be most potent selective inhibitor with an IC50 value 150 nM. Some these showed antiproliferative activity in several tumor cell lines (HCT116, MCF7, B16). Amongst all tested their anticancer effect cancer lines, 5c emerged active MCF-7 line 13.7 μM; it exhibited cell-cycle arrest G2 phase, well promoted apoptosis. Additionally, we noted a significant reduction colony-forming capability cells presence 5c. At intracellular level, was enumerated by monitoring acetylation α-tubulin limited acetyl-H3. Importantly, obtained results suggested at sub-micromolar concentrations compared other molecules vitro.

Language: Английский

Citations

9