Synthesis and evaluation of camphor and cytisine-based cyanopyrrolidines as DPP-IV inhibitors for the treatment of type 2 diabetes mellitus

Kuranov, Sergey; Tsypysheva, I. P.; Хвостов, Михаил В.; Зайнуллина, Л. Ф.; Borisevich, Sophia S.; Vakhitova, Yu. V.; Luzina, O. A.; Salakhutdinov, N. F.

doi:10.1016/j.bmc.2018.07.018

Cited by 25 publications

(7 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although there are many available treatments for T2DM [3], there is still a very urgent need to develop new drugs for the treatment of this disease. Recently, the clarification of the molecular mechanisms underlying the development of metabolic syndrome and the identification of novel targets for the prevention and therapy of T2DM have been widely studied by worldwide researchers [4–6]. It has now been clarified that the serum level of transforming growth factor β (TGF‐ β ) increased in patients with T2DM [7,8], and the TGF‐ β /Smad pathway was involved in the emergence of this disease.…”

Section: Introductionmentioning

confidence: 99%

SIS3, a good candidate for the reverse of type 2 diabetes mellitus in mice

Wang

Yan

Cui

et al. 2020

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

TGF‐β signaling plays an extremely important role in the occurrence and development of type 2 diabetes mellitus (T2DM), and the blockade of TGF‐β/Smad3 pathway protests against the high‐fat diet‐induced obesity and diabetes. As a specific small molecule inhibitor of Smad3 protein, the biological activities of compound SIS3 were evaluated by high‐fat diet‐induced T2DM model mice. In vivo results indicated that SIS3 can not only significantly reduce the body weight, fat mass, and fasting blood glucose in high‐fat diet‐induced T2DM model mice, but also improve insulin sensitivity and oral glucose tolerance of high‐fat diet‐induced T2DM model mice after the injection of SIS3 with 5 mg/kg for 45 days.

show abstract

Section: Introductionmentioning

confidence: 99%

SIS3, a good candidate for the reverse of type 2 diabetes mellitus in mice

Wang

Yan

Cui

et al. 2020

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…[24][25][26][27] Cytisine is an alkaloid that was found in plants and seeds of the Leguminosae (Fabaceae) family and has been shown to have several multipotent pharmacological activities. [13][14][15][16][17][18][19][20] However, there are NFATc1 is an important transcription factors in osteoclast differentiation. 10 NFATc1 is an NFAT family member that has been reported to modulate expression of several osteoclast-related genes including TRAP, cathepsin K and MMP-9.…”

Section: Discussionmentioning

confidence: 99%

“…12 It has been used to as a partial agonist of high-affinity acetylcholine receptors to withdraw nicotine cessation. 13 From the former research, we found that Cytisine has several pharmacological functions, such as anti-depressant like property, 14 anti-diabetes, 15 antivirus, 16 against human influenza virus A (H1N1) 16 and against cerebral ischemia-reperfusion 17 properties and so on. Furthermore, there has been reported that Cytisine alleviated liver fibrosis via PI3K/AKT/Smad pathway.…”

Section: Introductionmentioning

confidence: 99%

Cytisine attenuates bone loss of ovariectomy mouse by preventing RANKL‐induced osteoclastogenesis

Qian

Zhong

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

Postmenopausal Osteoporosis (PMOP) is oestrogen withdrawal characterized of much production and activation by osteoclast in the elderly female. Cytisine is a quinolizidine alkaloid that comes from seeds or other plants of the Leguminosae (Fabaceae) family. Cytisine has been shown several potential pharmacological functions. However, its effects on PMOP remain unknown. This study designed to explore whether Cytisine is able to suppress RANKL‐induced osteoclastogenesis and prevent the bone loss induced by oestrogen deficiency in ovariectomized (OVX) mice. In this study, we investigated the effect of Cytisine on RAW 264.7 cells and bone marrow monocytes (BMMs) derived osteoclast culture system in vitro and observed the effect of Cytisine on ovariectomized (OVX) mice model to imitate postmenopausal osteoporosis in vivo. We found that Cytisine inhibited F‐actin ring formation and tartrate‐resistant acid phosphatase (TRAP) staining in dose‐dependent ways, as well as bone resorption by pit formation assays. For molecular mechanism, Cytisine suppressed RANK‐related trigger RANKL by phosphorylation JNK/ERK/p38‐MAPK, IκBα/p65‐NF‐κB, and PI3K/AKT axis and significantly inhibited these signalling pathways. However, the suppression of PI3K‐AKT‐NFATc1 axis was rescued by AKT activator SC79. Meanwhile, Cytisine inhibited RANKL‐induced RANK‐TRAF6 association and RANKL‐related gene and protein markers such as NFATc1, Cathepsin K, MMP‐9 and TRAP. Our study indicated that Cytisine could suppress bone loss in OVX mouse through inhibited osteoclastogenesis. All data provide the evidence that Cytisine may be a promising agent in the treatment of osteoclast‐related diseases such as osteoporosis.

show abstract

“…[27] Camphor-based cyanopyrrolidines were identified as dipeptidyl peptidase IV (DPPIV) inhibitors for treating type 2 diabetes mellitus. [28] In continuing our search for new compounds endowed with anticancer activity, camphor was selected as a building block to construct thiosemicarbazones. Besides, in biological and medical fields, the α,β-unsaturated carbonyl scaffold has been deemed as one of prepotent structures.…”

Section: Introductionmentioning

confidence: 99%

Camphor-Based Thiosemicarbazone Analogues Induced G2 Cell Cycle Arrest and Apoptosis via Reactive Oxygen Species (ROS)-Mediated Mitochondrial Pathway in Human Breast Cancer Cells

Zhang¹,

Yunyun²,

Zhao³

et al. 2020

Chin. J. Org. Chem.

View full text Add to dashboard Cite

摘要以樟脑为原料合成了 22 个樟脑基缩氨基硫脲衍生物, 通过 1 H NMR、 13 3s)对 MDA-MB-231 细胞表现出最强的抗肿瘤活性[IC 50 ＝(3.90±0.04) µmol•L -1 ]. 此外, 初步的抗肿瘤机制结果表明, 化合物 3s 可以通过细胞内活性氧 (ROS)的增加和线粒体膜电位的破坏, 诱导 MDA-MB-231 细胞的 G2 期阻滞和剂量依赖式凋亡, 且通过凋亡相关蛋白的变化对实验结果进行了验证.

show abstract

Synthesis and evaluation of camphor and cytisine-based cyanopyrrolidines as DPP-IV inhibitors for the treatment of type 2 diabetes mellitus

Cited by 25 publications

References 23 publications

SIS3, a good candidate for the reverse of type 2 diabetes mellitus in mice

SIS3, a good candidate for the reverse of type 2 diabetes mellitus in mice

Cytisine attenuates bone loss of ovariectomy mouse by preventing RANKL‐induced osteoclastogenesis

Camphor-Based Thiosemicarbazone Analogues Induced G2 Cell Cycle Arrest and Apoptosis via Reactive Oxygen Species (ROS)-Mediated Mitochondrial Pathway in Human Breast Cancer Cells

Contact Info

Product

Resources

About