Nitrophenyl-group-containing Heterocycles. 3. New Isoquinolines, as antiprolifative agents against MCF7and HEGP2 Cell lines. Synthesis, characterization and biological Evaluation. DOI Creative Commons
Etify A. Bakhite, Reda Hassanien, Nasser Farhan

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

Abstract In this study, new tetrahydrosoquinoline compounds were synthesized by reacted with methyl iodide, chloro acetonitrile, ethyl chloroacetate, N-arylchloroacetamides N-and (benzthiazol-2-yl)-2-chloroacetamide reagents to gave tetrahydroiso-quinolin-3-ylthio) acetamides (5a-c) which can cyclized (6a-c) in excellent yields. The structures of all newly characterized elemental and spectral analyses. Also, most the evaluated for their anticancer activity MCF7 HEPG2 cell lines. From result we found that potent compound against lines was 9b, active 3. Then effects 3 on HEPG2 line investigated using an apoptotic Annexin V-FITC test flow cytometry. Compound induced a 59-fold increase apoptosis cycle arrested at G0-G1, G2/M phases. Moreover, molecular docking study applied showed 9b bind RET enzyme binding energies -6.8 kcal/mol comparison standard alectinib, exhibits energy -7.2 kcal/mol. HSP 90 (ΔG) -6.8 kcal/mol, is comparable Onalespib (-7.1 kcal/mol).

Language: Английский

Cyclometalated iridium(III) complex based on isoquinoline alkaloid synergistically elicits the ICD response and IDO inhibition via autophagy-dependent ferroptosis DOI Creative Commons
Lu Yuan, Shanshan Wang,

Mengya Li

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 15(1), P. 424 - 437

Published: June 25, 2024

The development of anticancer drugs to treat triple-negative breast cancer (TNBC) is an ongoing challenge. Immunogenic cell death (ICD) has garnered considerable interest worldwide as a promising synergistic modality for chemoimmunotherapy. However, only few or treatment modalities can trigger ICD response and none them exert clinical effect against TNBC. Therefore, new agents with potentially effective chemoimmunotherapeutic are required. In this study, five cyclometalated Ir(III) complexes containing isoquinoline alkaloid CˆN ligands were designed synthesized. Among them, Ir-1 exhibited the highest in vitro cytotoxicity. Mechanistically, could autophagy-dependent ferroptosis subsequent ferroptosis-dependent well indoleamine 2,3-dioxygenase (IDO) inhibition via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress MDA-MB-231 cells. When immunocompetent BALB/c mice vaccinated Ir-1-treated dying TNBC cells, antitumor CD8+ T-cell Foxp3+ depletion induced, resulting long-lasting immunity Moreover, combination therapy anti-PD1 substantially augment vivo therapeutic effects. Based on these results, candidate chemoimmunotherapy its effects mediated synergistically induction IDO blockage.

Language: Английский

Citations

9
Discovery of a Novel EF24 Analogue-Conjugated Pt(IV) Complex as Multi-Target Pt(IV) Prodrugs Aims to Enhance Anticancer Activity and Overcome Cisplatin Resistance DOI
Meng Wang,

Guimei Li,

Nan Xu

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Acquired resistance in cancer remains a significant challenge oncology, posing obstacles to the efficacy of diverse therapeutic approaches. The nuclear factor-kappa B (NF-κB) signaling pathway plays an important role development drug tumor cells. Herein, we employed NF-κB inhibitors and cisplatin synthesize multitarget Pt(IV) antitumor prodrugs. Among them, antiproliferation activity complex 8 demonstrated remarkable 146.92-time increase compared against A549/CDDP Moreover, could effectively induce DNA damage, promote ROS generation, autophagy, trigger mitochondrial apoptosis pathway, suppress cell proliferation through pathway. Furthermore, downregulated levels VEGF HIF-1α exerted antiproliferative PI3K/AKT STAT-3 Interestingly, showed superior vivo than cisplatin, 5a, or their combination, suggesting its potential as promising candidate for further lung treatment.

Language: Английский

Citations

0
New tetrahydroisoquinolines bearing nitrophenyl group targeting HSP90 and RET enzymes: synthesis, characterization and biological evaluation DOI Creative Commons
Etify A. Bakhite, Reda Hassanien, Nasser Farhan

et al.

BMC Chemistry, Journal Year: 2025, Volume and Issue: 19(1)

Published: Feb. 21, 2025

Abstract In this study, new tetrahydroisoquinoline compounds were synthesized by reaction of 7-Acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8- (3-nitrophenyl or 4-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2 H )-thiones with methyl iodide, chloro acetonitrile, ethyl chloroacetate to produce 3–5 and reacted N -arylchloroacetamides reagents gave tetrahydroisoquinolin-3-ylthio) acetamides 6a – c , 8a b which can cyclized 6,7,8,9-tetrahydrothieno[2,3-c]Isoquinoline-2-carboxamides 7a c, 9a . Also react -(benzthiazol-2-yl)-2-chloroacetamideto give compound 10 The structures all newly characterized elemental spectral analyses. Also, most the evaluated for their anticancer activities aganist MCF7 HEPG2 cell lines From result we found that active against was 8b, 3. Then effects 3 on line investigated using an apoptotic Annexin V-FITC test flow cytometry. Compound induced a 59-fold increase in apoptosis cycle arrested at G0-G1, G2/M phases. Moreover, molecular docking study applied showed 8b bind RET enzyme binding energies − 6.8 kcal/mol comparison standard alectinib exhibits energy 7.2 kcal/mol. HSP 90 (ΔG) kcal/mol, comparable Onalespib (− 7.1 kcal/mol). Graphical

Language: Английский

Citations

0
Rh(III)-Catalyzed Redox-Neutral C–H Activation/Annulation of Oxadiazolones with Sulfoxonium Ylides to access oxadiazoloisoquinolinone DOI

Pothapragada S. K. Prabhakar Ganesh,

Eswaran Kamaraj,

Vairaperumal Veeramani

et al.

New Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Oxadiazolone-fused isoquinolines were synthesized via Rh( iii )-catalyzed [4+2] annulation and C–H activation, followed by acymethylation products with antidiabetic anti-inflammatory potential.

Language: Английский

Citations

0
Iron-Dependent Cell Death: Exploring Ferroptosis as a Unique Target in Triple-Negative Breast Cancer Management DOI Creative Commons

L. Tan,

Jiaxing Liu, C Ma

et al.

Cancer Management and Research, Journal Year: 2025, Volume and Issue: Volume 17, P. 625 - 637

Published: March 1, 2025

Triple-negative breast cancer (TNBC) is characterized by aggressive behavior, high metastatic potential, and frequent relapses, presenting significant treatment challenges. Ferroptosis, a unique form of programmed cell death marked iron-dependent lipid peroxidation, has emerged as crucial factor in biology. Recent studies indicate that TNBC cells possess distinct metabolic profile linked to iron glutathione, which may render them more susceptible ferroptosis than other subtypes. Moreover, plays role the interactions between immune tumor cells, suggesting its potential modulate microenvironment influence response against TNBC.Evidence reveals not only affects viability but also alters promoting release damage-associated molecular patterns (DAMPs), can recruit site. Specific ferroptosis-related genes biomarkers, such ACSL4 GPX4, demonstrate altered expression tissues, offering promising avenues for diagnostic prognostic applications. Furthermore, preclinical models, induction been shown enhance efficacy existing therapies, indicating synergistic effect could be harnessed therapeutic benefit. The compelling link underscores novel target. Future research should focus on developing strategies exploit conjunction with traditional including identification natural compounds efficacious inducers personalized regimens. This review elucidates multifaceted implications TNBC, providing valuable insights improving both diagnosis this formidable subtype.

Language: Английский

Citations

0
Recent progress in stimuli‐activable metallo‐prodrugs for cancer therapy DOI Creative Commons
Jinzhe Liang,

Fangmian Wei,

Hui Chao

et al.

Smart Molecules, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 29, 2024

Abstract The clinical approval of platinum‐based drugs has prompted the development novel metallo‐complexes during last several decades, while severe problems, especially for poor water solubility, drug resistance and toxicity in patients, greatly hindered trials curative efficacy. To address these issues, concept metallo‐prodrugs been proposed oncology. Some stimuli‐activable provide new insights designing preparing site‐specific prodrugs with maximized therapeutic efficacy negligible unfavorable by‐effects. In this review, recent progress past 20 years overviewed, where endogenous exogenous stimuli have involved. Typical examples smart are discussed regarding to their molecular structure, activation mechanism, promising biomedical applications. end, challenges future perspectives discussed.

Language: Английский

Citations

3
The application of alkaloids in ferroptosis: A review DOI Creative Commons

Bocheng Fan,

Qihao Guo,

Shu Wang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117232 - 117232

Published: Aug. 3, 2024

Language: Английский

Citations

2
Nitrophenyl-group-containing Heterocycles. 3. New Isoquinolines, as antiprolifative agents against MCF7and HEGP2 Cell lines. Synthesis, characterization and biological Evaluation. DOI
Etify A. Bakhite, Reda Hassanien, Nasser Farhan

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 9, 2024

Abstract In this study, 7-Acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8- (3-nitrophenyl or 4-nitrophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2H)-thiones 2a-b were synthesized and used as starting materials. Thus, compounds reacted with methyl iodide, ethyl chloroacetate, by heating in ethanol the presence of sodium acetate trihydrate to give 3-substituted methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles 3, 4, respectively. a similar manner, reaction with N-arylchloroacetamides5a-c afforded corresponding N-aryl-(5,6,7,8-tetrahydroiso-quinolin-3-ylthio) acetamides 6a-c excellent yields. contrast, 3b N-(benzthiazol-2-yl)-2-chloroacetamide (12)under same (above) conditions yielded 1-amino-N-(benzthiazol-2-yl)-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxamide13.Cyclization into their 7a-cwas performed containing catalytic amount ethoxide. The structures all newly synthesized were characterized elemental and spectral analyses. Also, most evaluated for anticancer activity in MCF7 andHEGP2 cell lines.The potent compound against theMCF7 cell lines was 9b, HEGP2 3. Then effects 3 on proliferation HEPG2 investigated using an apoptotic Annexin V-FITC test flow cytometry. Compound induced 59-fold increase HEPG2 line apoptosis cycle arrested at G0-G1, G2/M phases.

Language: Английский

Citations

0
TTFA-Platin Conjugate: Deciphering the Therapeutic Roles of Combo-Prodrug through Evaluating Stability–Activity Relationship DOI
Megha Biswas,

K. D. Chaudhary,

Swati Shree Padhi

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

This work introduces a novel Pt(II) based prodrug TTFA-Platin that integrates β-diketonate ligand TTFA with platinum scaffold to structurally resemble carboplatin and offers intermediate kinetic lability between cisplatin carboplatin, striking balance therapeutic efficacy safety. A comprehensive stability speciation study was conducted in various biological media, mapping the effects of TTFA-Platin. control molecule, TMK-Platin, synthesized further validate structural-stability relationship, which displayed poor activatable features systems.

Language: Английский

Citations

0
Nrf2 Protects Against Acute Lung Injury by Inhibiting Ncoa4-Mediated Ferritinophagy Via Ube3b DOI

Yanjun Wang,

Hui Dong, Yunfan Gu

et al.

Published: Jan. 1, 2024

Language: Английский

Citations

0