New drug discovery and development from natural products: Advances and strategies

Pharmacology & Therapeutics, Год журнала: 2024, Номер 264, С. 108752 - 108752

Опубликована: Ноя. 16, 2024

Язык: Английский

---

Unlocking the therapeutic mechanism of Caesalpinia sappan: a comprehensive review of its antioxidant and anti-cancer properties, ethnopharmacology, and phytochemistry

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 7, 2025

Herbal medicine are an invaluable reservoir of bioactive compounds, offering immense potential for novel drug development to address a wide range diseases. Among these, Caesalpinia sappan has gained recognition its historical medicinal applications and substantial therapeutic potential. This review explores the ethnopharmacological significance, phytochemical composition, pharmacological properties C. sappan, with particular focus on anticancer activities. Traditionally, been utilized treating respiratory, gastrointestinal, inflammatory conditions, demonstrating broad scope. The plant's rich array compounds-flavonoids, triterpenoids, phenolic acids, glycosides-forms basis potent antioxidant, anti-inflammatory, effects. Modern research further substantiated versatility, revealing anticancer, anti-diabetic, anti-infective, hepatoprotective properties. However, significant challenges remain, including need unravel precise molecular mechanisms underlying effects, refine extraction isolation methods validate safety efficacy through well-designed clinical trials. Particularly noteworthy is sappan's in combination therapies, where it may synergistically target multiple cancer pathways, enhance outcomes, mitigate adverse synthesizes findings from past decade, providing comprehensive evaluation promise while identifying critical areas future research. By addressing these gaps, could serve as cornerstone innovative strategies, hope improved management other complex

Язык: Английский

---

Kushenol O Regulates GALNT7/NF-κB axis-Mediated M2 Macrophage Polarization and Efferocytosis in Papillary Thyroid Carcinoma

Phytomedicine, Год журнала: 2025, Номер 138, С. 156373 - 156373

Опубликована: Янв. 14, 2025

Язык: Английский

---

Anti-tumor pharmacology of natural products targeting mitosis

Cancer Biology and Medicine, Год журнала: 2022, Номер 19(6), С. 1 - 28

Опубликована: Июнь 15, 2022

Cancer has been an insurmountable problem in the history of medical science. The uncontrollable proliferation cancer cells is one cancer’s main characteristics, which closely associated with abnormal mitosis. Targeting mitosis effective method for treatment. This review summarizes several natural products anti-tumor effects related to mitosis, focusing on targeting microtubulin, inducing DNA damage, and modulating mitosis-associated kinases. Furthermore, disadvantages typical compounds, including drug resistance, toxicity non-tumor tissues, poor aqueous solubility pharmacokinetic properties, are also discussed, together strategies address them. Improved understanding cell may pave way development treatment cancer.

Язык: Английский

---

Licochalcone D exhibits cytotoxicity in breast cancer cells and enhances tumor necrosis factor‐related apoptosis‐inducing ligand‐induced apoptosis through upregulation of death receptor 5

Journal of Biochemical and Molecular Toxicology, Год журнала: 2024, Номер 38(7)

Опубликована: Июнь 27, 2024

Anticancer strategies using natural products or derivatives are promising alternatives for cancer treatment. Here, we showed that licochalcone D (LCD), a flavonoid extracted from Glycyrrhiza uralensis Fisch, suppressed the growth of breast cells, and was less toxic to MCF-10A normal cells. LCD-induced DNA damage, cell cycle arrest, apoptosis in Furthermore, LCD potentiated tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cytotoxicity. Mechanistically, revealed reduce survival protein expression upregulate death receptor 5 (DR5) expressions. Silencing DR5 blocked ability sensitize cells TRAIL-mediated apoptosis. increased CCAAT/enhancer-binding homologous (CHOP) Knockdown CHOP attenuated upregulation triggered by cotreatment with TRAIL. phosphorylation extracellular signal-regulated kinase promoted c-Jun amino-terminal (JNK) p38 mitogen-activated (MAPK). Pretreatment JNK inhibitor SP600125 MAPK SB203580 abolished CHOP, also plus TRAIL-induced cleavage poly(ADP-ribose) polymerase. Overall, our results show exerts cytotoxic effects on arguments inhibiting upregulating JNK/p38 MAPK-CHOP-dependent manner.

Язык: Английский

---

Design, synthesis, and biochemical and computational screening of novel oxindole derivatives as inhibitors of Aurora A kinase and SARS-CoV-2 spike/host ACE2 interaction

Medicinal Chemistry Research, Год журнала: 2024, Номер 33(4), С. 620 - 634

Опубликована: Март 5, 2024

Abstract Isatin (indol-2,3-dione), a secondary metabolite of tryptophan, has been used as the core structure to design several compounds that have tested and identified potent inhibitors apoptosis, potential antitumor agents, anticonvulsants, antiviral agents. In this work, analogs isatin hybrids synthesized characterized, their activities were established both Aurora A kinase severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike/host angiotensin-converting enzyme II (ACE2) interactions. Amongst hybrids, 6a , 6f 6g 6m exhibited inhibitory (with IC 50 values < 5 $$\mu$$ μ M), with GScore −7.9, −7.6, −8.2 −7.7 kcal/mol, respectively. Compounds 6i showed in blocking SARS-CoV-2 spike/ACE2 binding range 30 −6.4 −6.6 capable inhibiting kinase. Pharmacophore profiling indicated compound tightly fits pharmacophores, while 6d 6l pharmacophore. This work is proof concept some existing cancer drugs may possess properties. Molecular modeling active for each protein adopted different modes, hence interacting set amino acid residues site. The weaker against could be explained by small sizes ligands fail address important interactions ACE2 receptor

Язык: Английский

---

Genistein exerts anti-colorectal cancer actions: clinical reports, computational and validated findings

Aging, Год журнала: 2023, Номер 15(9), С. 3678 - 3689

Опубликована: Май 7, 2023

Colorectal cancer (CRC) is presently a health challenge in China. Although clinical chemotherapy prescribed availably, the negative effects and poor prognoses still occur. Genistein has antitumor properties our previous studies. However, molecular mechanisms underlying anti-CRC of genistein remain unclear. Increasing evidences have indicated that induction autophagy, one cell death models, closely associated with formation development human cancer. In current study, systematic bioinformatics approach using network pharmacology docking imitation was aimed at identifying pharmacological targets genistein, characterized by autophagy-related processes pathways. Moreover, experimental validation conducted culture samples. All 48 potential genistein-anti-CRC-associated autophagy were screened accordingly. Further analyses identified 10 core genistein-anti-CRC related to enrichment-assayed results revealed biological these might regulate multiple pathways, including estrogen signaling pathway. Additionally, data demonstrated high affinity for epidermal growth factor receptor (EGFR) 1 (ESR1). Both EGFR ESR1 proteins highly expressed CRC Preliminary vitro showed effectively reduced cellular proliferation, activated apoptosis, suppressed protein expressions cells. Our research findings uncovered against CRC, drug treatment validated experimentally, ESR1.

Язык: Английский

---

Silvestrol, a potent anticancer agent with unfavourable pharmacokinetics: Current knowledge on its pharmacological properties and future directions for the development of novel drugs

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 177, С. 117047 - 117047

Опубликована: Июль 2, 2024

Язык: Английский

---

NCAPD2 promotes the malignant progression of oral squamous cell carcinoma via the Wnt/β-catenin pathway

Cell Cycle, Год журнала: 2024, Номер 23(5), С. 588 - 601

Опубликована: Март 3, 2024

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with a poor prognosis, yet underlying mechanism needs further exploration. Non-SMC condensin I complex subunit D2 (NCAPD2) widely expressed protein in OSCC, but its role tumor development unclear. This study aimed to explore NCAPD2 expression and biological function OSCC. OSCC lines tissue specimens was analyzed using quantitative polymerase chain reaction, western blotting, immunohistochemistry. Cancer growth evaluated proliferation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, colony formation assays. Cell migration wound healing Transwell Apoptosis detected flow cytometry. The influence on vivo mouse xenograft model. significantly higher than that normal tissue. In vitro, knockdown inhibited proliferation promoted apoptosis. depletion also cells. Moreover, overexpression induced inverse effects phenotypes. vivo, we demonstrated downregulating could inhibit tumorigenicity Mechanically, regulation by involved Wnt/β-catenin signaling pathway. These results suggest as novel oncogene an important candidate therapeutic target for

Язык: Английский

---

Hesperidin enhanced anti-breast cancer effect and alleviated cisplatin induced nephrotoxicity through silk fibroin delivery system

Toxicology and Applied Pharmacology, Год журнала: 2025, Номер 495, С. 117234 - 117234

Опубликована: Янв. 18, 2025

Язык: Английский

---