scholarly journals Structure-Based Design of Novel Benzimidazole Derivatives as Pin1 Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1198 ◽  
Author(s):  
Shuxiang Wang ◽  
Lihong Guan ◽  
Jie Zang ◽  
Kun Xing ◽  
Jian Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antiproliferative Activity ◽  
Inhibitory Activity ◽  
Benzimidazole Derivatives ◽  
Human Prostate Cancer ◽  
Oncogenic Signaling ◽  
Oncogenic Pathways ◽  
Ic50 Values ◽  
Oncogenic Signaling Pathways

Peptidyl-prolyl cis/trans isomerase Pin1 plays a key role in amplifying and translating multiple oncogenic signaling pathways during oncogenesis. The blockade of Pin1 provided a unique way of disrupting multiple oncogenic pathways and inducing apoptosis. Aiming to develop potent Pin1 inhibitors, a series of benzimidazole derivatives were designed and synthesized. Among the derivatives, compounds 6h and 13g showed the most potent Pin1 inhibitory activity with IC50 values of 0.64 and 0.37 μM, respectively. In vitro antiproliferative assay demonstrated that compounds 6d, 6g, 6h, 6n, 6o and 7c exhibited moderate antiproliferative activity against human prostate cancer PC-3 cells. Taken together, these unique benzimidazole derivatives exhibited great potential to be further explored as potent Pin1 inhibitors with improved potency.

Modified tetrahalogenated benzimidazoles with CK2 inhibitory activity are active against human prostate cancer cells LNCaP in vitro

2012 ◽  
Vol 20 (14) ◽  
pp. 4390-4396 ◽  
Author(s):  
Carolin C. Schneider ◽  
Sabine Kartarius ◽  
Mathias Montenarh ◽  
Andrzej Orzeszko ◽  
Zygmunt Kazimierczuk
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Inhibitory Activity ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells

scholarly journals Inhibitory activity of apogossypol in human prostate cancer in vitro and in vivo

2015 ◽  
Vol 11 (6) ◽  
pp. 4142-4148 ◽  
Author(s):  
WENHUA ZHAN ◽  
XINGBIN HU ◽  
JING YI ◽  
QUNXING AN ◽  
XIAOFENG HUANG
Keyword(s):  
Prostate Cancer ◽  
Inhibitory Activity ◽  
Human Prostate ◽  
Human Prostate Cancer

Britanin Exhibits Potential Inhibitory Activity on Human Prostate Cancer Cell Lines Through PI3K/Akt/NF-κB Signaling Pathways

Planta Medica ◽  
2020 ◽  
Vol 86 (18) ◽  
pp. 1401-1410
Author(s):  
Qi Zeng ◽  
Yun Zeng ◽  
Yonghua Zhan ◽  
Xu Nie ◽  
Yingying Guo
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Inhibitory Activity ◽  
Prostate Cancer Cell ◽  
Human Prostate Cancer ◽  
Human Prostate Cancer Cell ◽  
Prostate Cancer Cell Lines

AbstractBritanin, a natural pseudoguaiacane sesquiterpene lactone, has significant antioxidant and anti-inflammatory activity, but little is known about its tumor inhibitory activity and the underlying mechanism. Here, we demonstrated in vitro and in vivo that britanin inhibited the growth of human prostate cancer cell lines (PC-3, PC-3-LUC, and DU-145). Through in vitro study, the results showed that britanin significantly decreased cell proliferation, migration, and motility. The moderate toxicity of britanin was determined with an acute toxicity study. A luciferase-labeled animal tumor xenograft model and bioluminescence imaging were applied, combining with biological validation for assessing the tumor progression. In vivo results demonstrated that britanin inhibited the growth of PC-3-LUC. The interleukin-2 level in mice was upregulated by britanin, which indicated that britanin induced antitumor immune activation. In addition, britanin downregulated the expression of nuclear factor (NF)-κB p105/p50, pp65, IκBα, pIκBα, phosphoinositide 3-kinase, pPI3k, Akt (protein kinase B, PKB), and pAkt proteins and upregulated expression of Bax. We discovered that britanin inhibits the growth of prostate cancer cells both in vitro and in vivo by regulating PI3K/Akt/NF-κB-related proteins and activating immunity. These findings shed light on the development of britanin as a promising agent for prostate cancer therapy.

scholarly journals Design, Synthesis and Bioactivity Evaluation of 4,6-Disubstituted Pyrido[3,2-d]pyrimidine Derivatives as Mnk and HDAC Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4318
Author(s):  
Kun Xing ◽  
Jian Zhang ◽  
Yu Han ◽  
Tong Tong ◽  
Dan Liu ◽  
...  
Keyword(s):  
Hydroxamic Acid ◽  
Hdac Inhibitors ◽  
Docking Study ◽  
Human Prostate Cancer ◽  
Pyrimidine Derivatives ◽  
Oncogenic Signaling ◽  
Design Synthesis ◽  
Dual Inhibitors ◽  
Oncogenic Signaling Pathways

Both HDACs and Mnks play important role in translating multiple oncogenic signaling pathways during oncogenesis. As HDAC and Mnk are highly expressed in a variety of tumors; thus simultaneous inhibit HDAC and Mnk can increase the inhibition of tumor cell proliferation and provide a new way of inhibiting tumor growth. Based on the previous work and the merge pharmacophore method; we designed and synthesized a series of 4,6-disubstituted pyrido[3,2-d]pyrimidine derivatives as HDAC and Mnk dual inhibitors. Among them; compound A12 displayed good HDAC and Mnk inhibitory activity. In vitro antiproliferative assay; compound A12 exhibited the best antiproliferative activity against human prostate cancer PC-3 cells. Docking study revealed that the pyrido[3,2-d]pyrimidine framework and hydroxamic acid motif of compound A12 were essential for maintaining the activity of HDAC and Mnk. These result indicated that A12 was a potent Mnk /HDAC inhibitor and will be further researched.

scholarly journals Potential Anticancer Lipoxygenase Inhibitors from the Red Sea-Derived Brown Algae Sargassum cinereum: An In-Silico-Supported In-Vitro Study

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 416
Author(s):  
Sami I. Alzarea ◽  
Abeer H. Elmaidomy ◽  
Hani Saber ◽  
Arafa Musa ◽  
Mohammad M. Al-Sanea ◽  
...  
Keyword(s):  
Red Sea ◽  
Antiproliferative Activity ◽  
Inhibitory Activity ◽  
Brown Algae ◽  
In Silico ◽  
Active Sites ◽  
In Vitro Study ◽  
Lipoxygenase Inhibitors ◽  
Phytochemical Investigation

LC-MS-assisted metabolomic profiling of the Red Sea-derived brown algae Sargassum cinereum “Sargassaceae” dereplicated eleven compounds 1–11. Further phytochemical investigation afforded two new aryl cresol 12–13, along with eight known compounds 14–21. Both new metabolites, along with 19, showed moderate in vitro antiproliferative activity against HepG2, MCF-7, and Caco-2. Pharmacophore-based virtual screening suggested both 5-LOX and 15-LOX as the most probable target linked to their observed antiproliferative activity. The in vitro enzyme assays revealed 12 and 13 were able to inhibit 5-LOX more preferentially than 15-LOX, while 19 showed a convergent inhibitory activity toward both enzymes. Further in-depth in silico investigation revealed the molecular interactions inside both enzymes’ active sites and explained the varying inhibitory activity for 12 and 13 toward 5-LOX and 15-LOX.

scholarly journals Synthesis and Evaluation of the Tetracyclic Ring-System of Isocryptolepine and Regioiso-Mers for Antimalarial, Antiproliferative and Antimicrobial Activities

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3268
Author(s):  
Katja S. Håheim ◽  
Emil Lindbäck ◽  
Kah Ni Tan ◽  
Marte Albrigtsen ◽  
Ida T. Urdal Helgeland ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antimicrobial Activities ◽  
Ring System ◽  
Human Prostate ◽  
The Novel ◽  
Human Prostate Cancer ◽  
Biofilm Inhibition

A series of novel quinoline-based tetracyclic ring-systems were synthesized and evaluated in vitro for their antiplasmodial, antiproliferative and antimicrobial activities. The novel hydroiodide salts 10 and 21 showed the most promising antiplasmodial inhibition, with compound 10 displaying higher selectivity than the employed standards. The antiproliferative assay revealed novel pyridophenanthridine 4b to be significantly more active against human prostate cancer (IC50 = 24 nM) than Puromycin (IC50 = 270 nM) and Doxorubicin (IC50 = 830 nM), which are used for clinical treatment. Pyridocarbazoles 9 was also moderately effective against all the employed cancer cell lines and moreover showed excellent biofilm inhibition (9a: MBIC = 100 µM; 9b: MBIC = 100 µM).

scholarly journals Mammalian Arginase Inhibitory Activity of Methanolic Extracts and Isolated Compounds from Cyperus Species

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1694
Author(s):  
Kamel Arraki ◽  
Perle Totoson ◽  
Alain Decendit ◽  
Andy Zedet ◽  
Justine Maroilley ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Methanolic Extract ◽  
Significant Inhibition ◽  
Isolation And Identification ◽  
Vasorelaxant Effect ◽  
Methanolic Extracts ◽  
Phytochemical Investigation ◽  
Ic50 Values ◽  
First Time

Polyphenolic enriched extracts from two species of Cyperus, Cyperus glomeratus and Cyperus thunbergii, possess mammalian arginase inhibitory capacities, with the percentage inhibition ranging from 80% to 95% at 100 µg/mL and 40% to 64% at 10 µg/mL. Phytochemical investigation of these species led to the isolation and identification of two new natural stilbene oligomers named thunbergin A-B (1–2), together with three other stilbenes, trans-resveratrol (3), trans-scirpusin A (4), trans-cyperusphenol A (6), and two flavonoids, aureusidin (5) and luteolin (7), which were isolated for the first time from C.thunbergii and C. glomeratus. Structures were established on the basis of the spectroscopic data from MS and NMR experiments. The arginase inhibitory activity of compounds 1–7 was evaluated through an in vitro arginase inhibitory assay using purified liver bovine arginase. As a result, five compounds (1, 4–7) showed significant inhibition of arginase, with IC50 values between 17.6 and 60.6 µM, in the range of those of the natural arginase inhibitor piceatannol (12.6 µM). In addition, methanolic extract from Cyperus thunbergii exhibited an endothelium and NO-dependent vasorelaxant effect on thoracic aortic rings from rats and improved endothelial dysfunction in an adjuvant-induced arthritis rat model.

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