Green One-Pot Synthesis of Thiazole Scaffolds Catalyzed by Reusable NiFe2O4 Nanoparticles: In Silico Binding Affinity and In Vitro Anticancer Activity Studies DOI Creative Commons

Satish Gudala,

Archi Sharma,

Aruna Lankada

и другие.

ACS Omega, Год журнала: 2024, Номер 9(36), С. 38262 - 38271

Опубликована: Авг. 29, 2024

A facile, green, one-pot multicomponent synthesis strategy was employed to fabricate novel thiazole scaffolds incorporating phthalazine, pyridazine, and pyrido-pyridazine derivatives (4a–4o). This synthetic route entailed the reaction of an α-halo carbonyl compound (1) with thiosemicarbazide (2) various anhydrides (3a–3o), utilizing NiFe2O4 nanoparticles as a reusable catalyst in ethanol:water (1:1) solvent system. The cytotoxicity synthesized compounds meticulously assessed against three cancer cell lines, A375, HeLa, MCF-7, employing IC50 values (μM) benchmark, compared reference drug erlotinib. Compound 4n displayed remarkable efficacy A375 (0.87 ± 0.31 μM), HeLa (1.38 1.24 MCF-7 (1.13 0.96 μM) significantly surpassing erlotinib's values. Additionally, 4k, 4l, 4m, 4o demonstrated notable across all tested indicating their potential effective anticancer agents. In silico docking studies Hsp82 Hsp90 proteins indicated that ligands 4c, 4j, 4o, 4l had superior binding affinities ADME analysis showed 4n, favorable pharmacokinetic profiles, including nontoxicity, high human intestinal absorption, low CYP inhibitory promiscuity. Structure–activity relationship revealed cyano benzylidene substitutions enhanced activity. Overall, compounds, particularly efficacy, interactions, promising making them strong candidates for further development

Язык: Английский

Unveiling the potential of isatin-grafted phenyl-1,2,3-triazole derivatives as dual VEGFR-2/STAT-3 inhibitors: Design, synthesis and biological assessments DOI

Heba A. Elsebaie,

Maha-Hamadien Abdulla,

Zainab M. Elsayed

и другие.

Bioorganic Chemistry, Год журнала: 2024, Номер 151, С. 107626 - 107626

Опубликована: Июль 10, 2024

Язык: Английский

Процитировано

8
Identification of indole-grafted pyrazolopyrimidine and pyrazolopyridine derivatives as new anti-cancer agents: Synthesis, biological assessments, and molecular modeling insights DOI
Wagdy M. Eldehna, Haytham O. Tawfik,

Maha-Hamadien Abdulla

и другие.

Bioorganic Chemistry, Год журнала: 2024, Номер 153, С. 107804 - 107804

Опубликована: Сен. 6, 2024

Язык: Английский

Процитировано

6
Design, Synthesis, Anticancer Screening, and Mechanistic Study of Spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide Derivatives DOI Open Access
Ahmed M. M. El‐Saghier, Hamada H. H. Mohammed,

Sherif A. Maher

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 863 - 863

Опубликована: Янв. 20, 2025

The present study aims to create spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives with anticancer activities. in vitro evaluation showed that only the novel spiro-acenaphthylene tethered-[1,3,4]-thiadiazole (compound 1) exhibited significant efficacy as a selective inhibitor of tumor-associated isoforms carbonic anhydrase. Compound 1 demonstrated considerable against renal RXF393, colon HT29, and melanoma LOX IMVI cancer cell lines, IC50 values 7.01 ± 0.39, 24.3 1.29, 9.55 0.51 µM, respectively. In comparison, doxorubicin 13.54 0.82, 13.50 0.71, 6.08 0.32 µM for corresponding lines. Importantly, compound lower toxicity normal WI 38 line than doxorubicin, 46.20 2.59 18.13 0.93 respectively, indicating greater selectivity target compared standard agent doxorubicin. Also, mechanistic experiments exhibits inhibitory activity human anhydrase hCA IX XII, 0.477 0.03 1.933 0.11 μM, enhanced cancer-associated over cytosolic I II, 7.353 0.36 12.560 0.74 Cell cycle studies revealed caused G1 phase arrest RXF393 cells, apoptosis verified substantial induction levels early late apoptosis, well necrosis (11.69%, 19.78%, 3.66%, respectively), comparable those induced by conventional cytotoxic at 9.91%, 23.37%, 6.16%, Molecular docking confirmed strong binding affinity active sites highlighting interactions zinc-binding groups hydrophobic residues. These findings underscore compound’s potential viable via targeting CA.

Язык: Английский

Процитировано

0
Design, synthesis, and molecular dynamics-driven evaluation of quinoline-sulfonamide derivatives as potent and selective EGFR inhibitors with promising anti-cancer efficacy and safety profiles DOI
Mahmoud S. Elkotamy, Mohamed K. Elgohary,

Islam A. Elkelesh

и другие.

Bioorganic Chemistry, Год журнала: 2025, Номер unknown, С. 108247 - 108247

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Development of novel amino-benzenesulfonamide derivatives and their analogues as carbonic anhydrase inhibitors: Design, synthesis, anticancer activity assessment, and pharmacokinetic studies using UPLC-MS/MS DOI
Khaled Elsayad, Ghada F. Elmasry, Sally Tarek Mahmoud

и другие.

Bioorganic Chemistry, Год журнала: 2025, Номер 159, С. 108335 - 108335

Опубликована: Март 6, 2025

Язык: Английский

Процитировано

0
Modulation of AMPK by esomeprazole and canagliflozin mitigates methotrexate-induced hepatotoxicity: involvement of MAPK/JNK/ERK, JAK1/STAT3, and PI3K/Akt signaling pathways DOI Creative Commons
Ahmed M. El‐Dessouki,

Mohamed E. Kaml,

Mohammed F. EL-Yamany

и другие.

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

Abstract This research investigated the hepatoprotective effects of esomeprazole (ESOM) and canagliflozin (CANA) against methotrexate-induced liver toxicity, focusing on AMPK modulation its regulation MAPK/JNK/ERK, JAK1/STAT3, PI3K/Akt pathways. Fifty male Wistar rats were divided into five groups: control, MTX, three pretreatment groups receiving ESOM (30 mg/kg), CANA or their combination. administered for 8 days before 1 day after a single MTX injection (20 mg/kg, intraperitoneally) 9 to induce hepatotoxicity. Liver injury, oxidative stress, inflammation, apoptosis assessed using biochemical, histopathological, immunohistochemical, qRT-PCR, western blot analyses. Data analyzed by one-way analysis variance (ANOVA) Tukey’s post hoc test, with significance at p < 0.05. Results presented as mean ± standard error (SE). Rats that received showed significant damage, marked elevated ALT, AST, MDA, MPO, iNOS, TNF-α, IL-6, IL-1β levels ( 0.01) decreased antioxidant enzymes (HO-1, Nrf2, GSH). Immunohistochemistry revealed increased NF-kB p65 caspase-9 expression 0.01), correlating histopathological changes. Pretreatment reduced enzyme levels, improved histology, restored balance, inhibited inflammatory pathways via p38MAPK/NF-kB JAK1/STAT3 0.01). Moreover, preserved activity prevented caspase-dependent Additionally, combination treatment synergistic effects, demonstrated improvements in all measured parameters. These findings suggested had potential therapeutic agents alleviating MTX-induced hepatotoxicity warranted further investigation future research.

Язык: Английский

Процитировано

0
Design and synthesis of novel substituted s‐triazines tethered benzenesulfonamides as potential antimicrobial candidates: Antibiofilm and bacterial protein permeability assessments DOI Open Access
Ahmed A. Al‐Karmalawy, Haytham O. Tawfik, Gharieb S. El‐Sayyad

и другие.

Archiv der Pharmazie, Год журнала: 2025, Номер 358(3)

Опубликована: Март 1, 2025

Abstract New s ‐triazine hydrazone hybrids ( 4a – 4r ) were designed and synthesized as promising microbial DNA gyrase inhibitors. This was done by taking the lead inhibitor (AstraZeneca arylaminotriazine) a reference. The novel samples subsequently tested antimicrobial agents against certain pathogenic bacteria unicellular fungi. antibiofilm potential membrane leakage test used to determine mechanism of response. minimum inhibitory concentration (MIC) values 4g , 4i between 62.5 250.0 µg/mL. MIC for candidate Staphylococcus aureus, Candida albicans, Enterobacter agglomerans Klebsiella pneumonia are 62.5, 125.0, µg/mL, respectively. Conversely, compound µg/mL C. albicans E. 125.0 S. aureus K. . Besides, molecular docking study performed validate both binding affinity mode newly analogs candidates toward bacterial receptors. nanocomposites had potentials, which encouraging their use in biomedical applications. Consequently, afforded compounds can be employed future optimization.

Язык: Английский

Процитировано

0
Melatonin augments anti-tumor activity and alleviates nephrotoxicity of gemcitabine in a pancreatic cancer xenograft model targeting P62/Keap1 pathway DOI Creative Commons
Samar Ibrahim,

Eman H. Yousef,

Ahmed M. El‐Dessouki

и другие.

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

Abstract Although gemcitabine is a primary chemotherapy for pancreatic cancer, its effectiveness limited by chemoresistance and nephrotoxicity, posing significant clinical challenges. Therefore, the development of novel therapeutic approaches to prevent malignancy remains crucial. This study aimed investigate potential melatonin in enhancing gemcitabine’s anticancer efficacy while mitigating nephrotoxic effects through modulation Keap1/p62 pathway. A cancer xenograft model was established rats, which received either (50 mg/kg, I.P.), or their combination three times per week 2 weeks. Our findings demonstrate that potentiates cancer-suppressing via Kelch-like-ECH associated protein-1 (Keap1)/p62 pathway, resulting reduced fibrosis, oxidative stress, inflammatory markers. Additionally, significantly mitigated gemcitabine-induced nephrotoxicity. These results suggest may serve as an adjuvant therapy treatment, reducing adverse effects.

Язык: Английский

Процитировано

0
Targeting DNA repair mechanisms: Spirobenzoxazinone and salicylamide derivatives as novel candidates for PARP-1 inhibition in cancer therapy DOI
Abdelrazak M. Kadry, Mai Adel,

Samar A. Abubshait

и другие.

Bioorganic & Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 118173 - 118173

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Shooting an Arrow against Convulsion: Novel Triazole-Grafted Benzenesulfonamide Derivatives as Carbonic Anhydrase II and VII Inhibitors DOI

Mohamed A. Zeidan,

Mahmoud Abdelrahman Alkabbani, Simone Giovannuzzi

и другие.

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

This study investigates new anticonvulsant substances that target the epilepsy-associated carbonic anhydrase isoforms II and VII. The 1,2,3-triazole with a benzenesulfonamide motif is present in produced molecules. Of these, 5b 5c exhibited remarkable selectivity inhibitory efficacy toward hCA VII over I. KI values of were 6.3 10.1 nM, respectively, 21.6 18.9 respectively. In pilocarpine-induced paradigm, vivo assessments showed decreased seizure severity susceptibility delayed onset diminished intensity. quick absorption stability demonstrated by pharmacokinetic investigations. Evaluations toxicity no neurotoxic effects high safety margin (LD50 > 2000 mg/kg). Mechanistic research has shown effectiveness maintaining neuronal integrity, reducing mTOR activation, raising hippocampus KCC2 levels. Compound 5b's binding interactions clarified docking dynamics experiments.

Язык: Английский

Процитировано

0