Design and synthesis of diosgenin derivatives as apoptosis inducers through mitochondria-related pathways

Ma, Liwei; Zhang, Jinling; Wang, Xuemei; Yang, Jifang; Guo, Liang; Wang, Xiaoli; Shopsin, Bo; Dong, Wei; Wang, Wenbao

doi:10.1016/j.ejmech.2021.113361

Cited by 34 publications

(25 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Total RNA was extracted from HepG2 cells using a Trizol™ reagent (Invitrogen, USA) and qRT-PCR was conducted on it, as documented before 24 . The purity and concentration of total RNA were checked using a spectrophotometer, in terms of A 260 nm/A 280 nm.…”

Section: Methodsmentioning

confidence: 99%

Design, synthesis and biological evaluation of novel diosgenin–benzoic acid mustard hybrids with potential anti-proliferative activities in human hepatoma HepG2 cells

Zhang

Wang

Tian

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

To discover new lead compounds with anti-tumour activities, in the present study, natural diosgenin was hybridised with the reported benzoic acid mustard pharmacophore. The in vitro cytotoxicity of the resulting newly synthesised hybrids ( 8 – 10 , 14a – 14f , and 15a – 15f ) was then evaluated in three tumour cells (HepG2, MCF-7, and HeLa) as well as normal GES-1 cells. Among them, 14f possessed the most potential anti-proliferative activity against HepG2 cells, with an IC 50 value of 2.26 µM, which was 14.4-fold higher than that of diosgenin (IC 50 = 32.63 µM). Furthermore, it showed weak cytotoxicity against GES-1 cells (IC 50 > 100 µM), thus exhibiting good antiproliferative selectivity between normal and tumour cells. Moreover, 14f could induce G0/G1 arrest and apoptosis of HepG2 cells. From a mechanistic perspective, 14f regulated cell cycle-related proteins (CDK2, CDK4, CDK6, cyclin D1 and cyclin E1) as well mitochondrial apoptosis pathway-related proteins (Bax, Bcl-2, caspase 9, and caspase 3). These findings suggested that hybrid 14f serves as a promising anti-hepatoma lead compound that deserves further research.

show abstract

Section: Methodsmentioning

confidence: 99%

Design, synthesis and biological evaluation of novel diosgenin–benzoic acid mustard hybrids with potential anti-proliferative activities in human hepatoma HepG2 cells

Zhang

Wang

Tian

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…[20] A broad single signal at δ H 7.22 was observed towards the low field, as well as a singlet signal at δ H 6.18, which was corresponded to the double bond proton HÀ 4. In the 13 CNMR spectrum, 28 signals were found, the signal of CÀ 3 at δ c 150.1, the signals of the double bonds CÀ 5 and CÀ 4 at δ c 140.7 and 112.2, and the spiroketal CÀ 22 at δ c 107.6 were observed (Figure 1).…”

Section: Synthesis Of Spirostanes Containing Hydroximino and [23-d] F...mentioning

confidence: 98%

“…In recent years, diosgenin is popularly used as a promising antitumor and anti-cancer agent. [13] Hence, synthetic modifications on the diosgenin skeleton have great importance to obtain novel biological active derivatives. For example, it was reported that C-3 and C-26 modifications in the diosgenin can modulate the antitumor property performed structure-activity relationship (SAR) analyses.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Structural Analysis and Antiproliferative Activity of Nitrogen‐Containing Hetero Spirostan Derivatives: Oximes, Heterocyclic Ring‐Fused and Furostanes

Erdagi

Yıldız

2022

ChemistrySelect

View full text Add to dashboard Cite

The present study focuses on the synthesis of spirostan derivatives as potential drug candidates for biological applications. Recently, spirostan derivatives containing the hetero‐atom have attracted great scientific attention due to their anti‐cancer, anti‐diabetes, and anti‐inflammatory properties. In this study, nitrogen‐containing novel spirostan derivatives with substituted oxime, nitrile, pyrazole, isoxazole structures in ring‐A and F were designed and synthesized starting from diosgenin. The intermediates and target derivatives’ chemical structures were characterized by FTIR, HRMS, 1HNMR, 13CNMR, elemental analysis, and HPLC techniques. The target compounds were evaluated for their cytotoxicities in two human cancer cell lines (MCF‐7 and A549). The tested compounds exhibited potent anticancer activity against human breast adenocarcinoma (MCF‐7) and lung adenocarcinoma (A549). On the other hand, the toxicity of the tested compounds against human healthy fetal lung fibroblasts (MCR‐5) indicated that compounds were non‐toxic for the human body. The results showed that compounds may be used as a promising agents for anticancer agents with improved efficacy.

show abstract

“…A total of 28 diosgenin amino acid ester derivatives (3a-3g and 7a-7g) were designed and synthesized by Ma et al and evaluated for their cytotoxicity against six human cancer cells including K562, T24, MNK45, HepG2, A549, and MCF-7 [ 98 ]. The majority of derivatives displayed cytotoxic potential against these six tumor cells.…”

Section: Pharmacological Properties Of Diosgenin: Underlying Molecula...mentioning

confidence: 99%

Diosgenin: An Updated Pharmacological Review and Therapeutic Perspectives

Semwal

Painuli

Abu-Izneid

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Plants including Rhizoma polgonati, Smilax china, and Trigonella foenum-graecum contain a lot of diosgenin, a steroidal sapogenin. This bioactive phytochemical has shown high potential and interest in the treatment of various disorders such as cancer, diabetes, arthritis, asthma, and cardiovascular disease, in addition to being an important starting material for the preparation of several steroidal drugs in the pharmaceutical industry. This review aims to provide an overview of the in vitro, in vivo, and clinical studies reporting the diosgenin’s pharmacological effects and to discuss the safety issues. Preclinical studies have shown promising effects on cancer, neuroprotection, atherosclerosis, asthma, bone health, and other pathologies. Clinical investigations have demonstrated diosgenin’s nontoxic nature and promising benefits on cognitive function and menopause. However, further well-designed clinical trials are needed to address the other effects seen in preclinical studies, as well as a better knowledge of the diosgenin’s safety profile.

show abstract

Design and synthesis of diosgenin derivatives as apoptosis inducers through mitochondria-related pathways

Cited by 34 publications

References 39 publications

Design, synthesis and biological evaluation of novel diosgenin–benzoic acid mustard hybrids with potential anti-proliferative activities in human hepatoma HepG2 cells

Design, synthesis and biological evaluation of novel diosgenin–benzoic acid mustard hybrids with potential anti-proliferative activities in human hepatoma HepG2 cells

Synthesis, Structural Analysis and Antiproliferative Activity of Nitrogen‐Containing Hetero Spirostan Derivatives: Oximes, Heterocyclic Ring‐Fused and Furostanes

Diosgenin: An Updated Pharmacological Review and Therapeutic Perspectives

Contact Info

Product

Resources

About