An insight into isatin and its hybrid scaffolds as anti-cancer agents: an explicative review DOI Creative Commons
Dipanjan Karati

Discover Chemistry., Journal Year: 2024, Volume and Issue: 1(1)

Published: Dec. 4, 2024

As a bioactive heterocyclic congener, isatin has wide range of pharmacological and biological uses. Due to their numerous potential uses, it is becoming increasingly important design inventive its analogs. Additionally, essential disclose groundbreaking techniques for synthesizing this nucleus, examine the various potencies that heterocycle, investigate uses isatin. One significant class chemotherapeutic medicines with ability overcome drug resistance are metal-based medications. The creation novel therapeutic medications distinct modes action required due rise in resistance, treatment failures, scarcity available treatments. Such derivatives, which target biomolecules or organelles, demonstrated encouraging antiproliferative capabilities against cancer cells when they were free ligands coupled metal ions. Its qualities typically enhanced binds ions, suggesting ligand modulating each other synergistic way. Isatin strong inhibitor enzymes receptors can induce apoptosis variety cell lines affect expression specific genes linked apoptosis. Hybridization promising approach discovery because hybrid molecules have improve specificity, increase efficiency. Several compounds now undergoing phases clinical trials. A growing number experts interested studying chemical properties isatin-heterocycle hybrids. Anti-cancer activity scaffolds reviewed. lead compounds, several analogues been created, functions assessed. development new, powerful resulting from combination pharmacophores molecule may facilitate compounds.

Language: Английский

Design and Synthesis of Topoisomerases-Histone Deacetylase Dual Targeted Quinoline-Bridged Hydroxamates as Anticancer Agents DOI
Gaurav Joshi, Umesh Prasad Yadav,

Zahid Rafiq

et al.

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

Published: Jan. 14, 2025

The multifactorial nature of cancer requires treatment that involves simultaneous targeting associated overexpressed proteins and cell signaling pathways, possibly leading to synergistic effects. Herein, we present a systematic study the inhibition human topoisomerases (hTopos) histone deacetylases (HDACs) by multitargeted quinoline-bridged hydroxamic acid derivatives. These compounds were rationally designed considering pharmacophoric features catalytic sites cross-talk proteins, synthesized, assessed for their anticancer potential. Our findings revealed compound 5c significantly produced effects in vitro vivo reducing tumor growth its size A549 cell-induced lung xenograft model through multiple mechanisms, primarily multi-inhibition hTopoI/II HDACs, especially HDAC1 via atypical binding. paper discusses detailed mechanistic biological investigations, structure-activity supported computational docking studies, DMPK studies provides future scope lead optimization modification.

Language: Английский

Citations

0
Repurposing Linezolid in Conjunction with Histone Deacetylase Inhibitor Access in the Realm of Glioblastoma Therapies DOI Creative Commons
I‐Chung Chen,

Hong-Yi Lin,

Zhengyang Liu

et al.

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

Published: Jan. 21, 2025

Since decades after temozolomide was approved, no effective drugs have been developed. Undoubtedly, blood–brain barrier (BBB) penetration is a severe issue that should be overcome in glioblastoma multiforme (GBM) drug development. In this research, we were inspired by linezolid through structural modification with several bioactive moieties to achieve the desired brain delivery. The results indicated histone deacetylase modification, referred as compound 1, demonstrated promising cytotoxic effects various tumor cell lines. Further comprehensive mechanism studies 1 induced acetylation, leading DNA double-strand breaks, and ubiquitination of RAD51, disrupting repair process. Furthermore, also exhibited dramatic improvement orthotopic GBM mouse model, demonstrating its efficacy satisfying BBB penetration. Therefore, reported provided an independent therapeutic pathway, elongation survival size reduction, ability penetrate BBB, potent further

Language: Английский

Citations

0
Clinical Applications of HDAC Inhibitors as Anticancer Agents in Prostate, Breast, Ovarian, and Cervical Cancers DOI
Saad Bakrim,

Farah Atifi,

Nasreddine El Omari

et al.

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(12)

Published: March 1, 2025

Abstract Alongside genetic events, epigenetic processes also have a considerable impact on cancer induction and progression. Histone acetyltransferases (HATs) histone deacetylases (HDACs) both coordinate to modulate modification via acetylation, an essential component of regulation concerning gene expression. In this context, HDAC inhibition has been extensively investigated as therapeutic approach discovering anticancer drugs. Nevertheless, it is still highly challenging design inhibitors (HDACis) that are successfully operational in solid tumors such prostate, breast, ovarian, cervical cancers. Today, some HDACis adopted by the U.S. Food Drug Administration (FDA) medically manage these malignancies, notably vorinostat, panobinostat, romidepsin, belinostat. addition, they promote immune response increasing expression tumor necrosis factor (TNF), interferon‐gamma receptor 1 (IFN‐γR1), programmed death ligand (PD‐L1) addition other signaling pathways. A deeper comprehension pathways will advance our knowledge defects tissue while opening up opportunities for innovative promising strategies based targeted therapies.

Language: Английский

Citations

0
Molecular docking and pharmacokinetic evaluations of curcumin-based scaffolds as MDM2-p53 inhibitors DOI Creative Commons

Santosh Prasad Chaudhary Kurmi,

Shankar Thapa, Dipanjan Karati

et al.

Discover Chemistry., Journal Year: 2025, Volume and Issue: 2(1)

Published: March 24, 2025

Language: Английский

Citations

0
HDAC inhibitors: Cardiotoxicity and paradoxical cardioprotective effect in ischemia-reperfusion myocardiocyte injury DOI Creative Commons
Kenneth K.W. To, Seda S. Tolu,

Longling Wang

et al.

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Histone deacetylase inhibitors (HDACIs) are epigenetic drugs that regulate the acetylation status of histones and non-histone proteins, thereby leading to chromatin remodeling transcriptional regulation key apoptotic cell cycle regulatory genes. There currently five HDACIs clinically approved by major authorities for treating hematological cancers, primarily as monotherapy. While have been particularly effective in T-cell lymphomas, their clinical efficacies not yet extended solid tumors. The development continues, including treatment a non-malignant conditions, with givinostat recently US FDA. However, early was limited concerns about cardiotoxicity QT interval prolongation. Yet, paradoxically, latest research suggests some cardioprotective effect ischemic heart disease or failure. This review presents update HDACIs. mechanisms HDACI-induced cardiotoxic adverse events strategies management discussed. We will also deliberate potential repurposing use HDAC isoform selectivity ischemia-reperfusion cardiac muscle injury, hypertrophy, fibrosis.

Language: Английский

Citations

0
3-Deazaneplanocin A (DZNep): A Drug That Deserves a Second Look DOI

Víctor E. Márquez

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(20), P. 17964 - 17979

Published: Oct. 11, 2024

The emerging data compiled during the past five years on 3-deazaneplanocin (DZNep) provide compelling evidence to reevaluate this drug as a better alternative over specific catalytic inhibitors of histone methyl transferases (HTMs). indirect mechanism DZNep via inhibition AdoHcy-ase, once considered liability due possible side effects, has now shown be rather beneficial additional pathways targeted by are important contributors its superior anticancer properties. Furthermore, demonstrated ability induce proteasomal degradation target and reduce toxicity in combination with well-established antitumor therapies animal models. In addition, effects suppressing fibrosis inflammation liver, kidney, peritoneum, airways. Finally, mRNA m

Language: Английский

Citations

2
Synthetic Approaches and Clinical Applications of Representative HDAC Inhibitors for Cancer Therapy: A Review DOI
Zhiyi Lv, Tianyi Ji, Jie Liu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 283, P. 117185 - 117185

Published: Dec. 20, 2024

Language: Английский

Citations

2
Enhancing MS‐275 Anticancer Activity: Encapsulation of MS‐275 in TPGS Micelles Demonstrated High Efficiency DOI Creative Commons
Abdulelah Saleh Alshawli, Tarek A. Ahmed, Farid Ahmed

et al.

Journal of Nanotechnology, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

MS‐275, a histone deacetylase inhibitor, has proven anticancer activities against various malignancies. However, its clinical application been constrained by dose‐limiting toxicity, off‐target effects, and variable outcomes. Clinical data suggest that sustained low MS‐275 doses could achieve more selective consistent effect. This study aimed at enhancing the activity of encapsulating it in D‐ α ‐tocopheryl polyethylene glycol 1000 succinate (TPGS) micelles. The produced nanoformulations were characterized their polydispersity (0.201), negative zeta potential (−0.397 mV), high entrapment efficiency (98.8%). Experimental evaluation formulation showed significant reduction HepG2, HCT116, MCF7 cells’ viability, associated with enhanced apoptosis lower IC 50 compared to alone. was further examined on cancer cells xenografted chorioallantoic membrane (CAM) chick embryos. results substantial tumor size. TPGS micelles alone induced an accumulation G1 slightly reduced cellular viability cell lines. Our represents promising strategy enhance therapeutic impact while minimizing pharmacological dosage.

Language: Английский

Citations

0
RCC1 regulation of subcellular protein localization via Ran GTPase drives pancreatic ductal adenocarcinoma growth DOI
Sahar F. Bannoura,

Amro Aboukameel,

Husain Yar Khan

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: unknown, P. 217275 - 217275

Published: Sept. 1, 2024

Language: Английский

Citations

0
SAL protects endothelial cells from H2O2-induced endothelial dysfunction: Regulation of inflammation and autophagy by EZH2 DOI Creative Commons

Sun Li,

Xuefang Li, Jie Zhang

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113060 - 113060

Published: Sept. 24, 2024

Language: Английский

Citations

0