2137-22-6Relevant articles and documents
Design, synthesis, and biological evaluation of diosgenin-indole derivatives as dual-functional agents for the treatment of Alzheimer's disease
Zhou, Li-Cheng,Liang, Ying-Fan,Huang, Yi,Yang, Gui-Xiang,Zheng, Lu-Lu,Sun, Jia-Min,Li, Yang,Zhu, Fu-Li,Qian, He-Wen,Wang, Rui,Ma, Lei
, (2021)
The complex pathogenesis of Alzheimer's disease (AD) has become a major obstacle in its treatment. An effective approach is to develop multifunctional agents that simultaneously target multiple pathological processes. Here, a series of diosgenin-indole compounds were designed, synthesized and evaluated for their neuroprotective effects against H2O2 (hydrogen peroxide), 6-OHDA (6-hydroxydopamine) and Aβ (beta amyloid) damages. Preliminary structure-activities relationship revealed that the introduction of indole fragment and electron-donating group at C-5 on ring indole could be beneficial for neuroprotective activities. Results indicated that compound 5b was the most promising candidate against cellular damage induced by H2O2 (52.9 ± 1.9%), 6-OHDA (38.4 ± 2.4%) and Aβ1-42 (54.4 ± 2.7%). Molecular docking study suggested the affinity for 5b bound to Aβ1-42 was ?40.59 kcal/mol, which revealed the strong binding affinity of 5b to Aβ1-42. The predicted values of brain/blood partition coefficient (?0.733) and polar surface area (85.118 ?2) indicated the favorable abilities of BBB permeation and absorption of 5b. In addition, 5b significantly decreased ROS (reactive oxygen species) production induced by H2O2. In the following in vivo experiment, 5b obviously attenuated memory and learning impairments of Aβ-injected mice. In summary, compound 5b could be considered as a promising dual-functional neuroprotective agent against AD.
Preparations of heterospirostanols and their pharmacological activities
Quan, Hang-Ji,Koyanagi, Jyunichi,Ohmori, Koichi,Uesato, Shinichi,Tsuchido, Tetsuaki,Saito, Setsuo
, p. 659 - 669 (2002)
(3β,20S,22S,25R)-22-Thiospirosol-5-en-3-ol (9) and (3β,20S,22S,25R)-22-seleno-spirosol-5-en-3-ol (11) were prepared from diosgenin (3) via 26-iodopseudodiosgenin (6) as a key intermediate. Diosgenone (15), solasodinone (16), (20S,22S,25R)-22-thio-spirosol
The efficient Δ1-dehydrogenation of a wide spectrum of 3-ketosteroids in a broad pH range by 3-ketosteroid dehydrogenase from Sterolibacterium denitrificans
Wojtkiewicz, Agnieszka M.,Wójcik, Patrycja,Procner, Magdalena,Flejszar, Monika,Oszajca, Maria,Hocho?owski, Mateusz,Tataruch, Mateusz,Mruga?a, Beata,Janeczko, Tomasz,Szaleniec, Maciej
, (2020)
Cholest-4-en-3-one Δ1-dehydrogenase (AcmB) from Sterolibacterium denitrificans, a key enzyme of the central degradation pathway of cholesterol, is a protein catalyzing Δ1-dehydrogenation of a wide range of 3-ketosteroids. In this study, we demonstrate the application of AcmB in the synthesis of 1-dehydro-3-ketosteroids and investigate the influence of reaction conditions on the catalytic performance of the enzyme. The recombinant AcmB expressed in E. coli BL21(DE3)Magic exhibits a broad pH optimum and pH stability in the range of 6.5 to 9.0. The activity-based pH optimum of AcmB reaction depends on the type of electron acceptor (2,6-dichloroindophenol - DCPIP, phenazine methosulfate - PMS or potassium hexacyanoferrate - K3[Fe(CN)6]) used in the biocatalytic process yielding the best kinetic properties for the reaction with a DCPIP/PMS mixture (kcat/Km = 1.4·105 s-1·M-1 at pH 9.0) followed by DCPIP (kcat/Km = 1.0·105 s-1·M-1 at pH = 6.5) and K3[Fe(CN)6] (kcat/Km = 0.5·102 s-1·M-1 at pH = 8.0). The unique feature of AcmB is its capability to convert both testosterone derivatives (C20–C22) as well as steroids substituted at C17 (C27-C30) such as cholest-4-en-3-one or (25R)-spirost-4-en-3-one (diosgenone). Apparent steady-state kinetic parameters were determined for both groups of AcmB substrates. In a batch reactor synthesis, the solubility of water-insoluble steroids was facilitated by the addition of a solubilizer, 2-hydroxypropyl-β-cyclodextrin, and organic co-solvent, 2-methoxyethanol. Catalytic properties characterization of AcmB was tested in fed-batch reactor set-ups, using 0.81 μM of isolated enzyme, PMS and aerobic atmosphere resulting in >99% conversion of the C17–C20 3-ketosteroids within 2 h. Finally, the whole cell E. coli system with recombinant enzyme was demonstrated as an efficient biocatalyst in the synthesis of 1-dehydro-3-ketosteroids.
Twin drug design, synthesis and evaluation of diosgenin derivatives as multitargeted agents for the treatment of vascular dementia
Yang, Gui-Xiang,Sun, Jia-Min,Zheng, Lu-Lu,Zhang, Li,Li, Jie,Gan, Hai-Xian,Huang, Yan,Huang, Jin,Diao, Xing-Xing,Tang, Yun,Wang, Rui,Ma, Lei
, (2021)
A novel series of multitargeted molecules were designed and synthesized by combining the pharmacological role of cholinesterase inhibitor and antioxidant of steroid as potential ligands for the treatment of Vascular Dementia (VD). The oxygen-glucose deprivation (OGD) model was used to evaluate these molecules, among which the most potent compound ML5 showed the highest activity. Firstly, ML5 showed appropriate inhibition of cholinesterases (ChEs) at orally 15 mg/kg in vivo. The further test revealed that ML5 promoted the nuclear translocation of Nrf2. Furthermore, ML5 has significant neuroprotective effect in vivo model of bilateral common carotid artery occlusion (BCCAO), significantly increasing the expression of Nrf2 protein in the cerebral cortex. In the molecular docking research, we predicted the ML5 combined with hAChE and Keap1. Finally, compound ML5 displayed normal oral absorption and it was nontoxic at 500 mg/kg, po, dose. We can draw the conclusion that ML5 could be considered as a new potential compound for VD treatment.
Steroid sapogenin derivative as well as preparation method and application thereof
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Paragraph 0130-0132; 0135-0136, (2020/11/09)
The invention discloses a steroid sapogenin derivative represented by general formula (1), and a pharmaceutically acceptable salt and a pharmaceutical composition thereof. The steroid sapogenin derivative disclosed by the invention has a protective effect
Diosgenone synthesis, anti-malarial activity and QSAR of analogues of this natural product
Pabon, Adriana,Escobar, Gustavo,Vargas, Esteban,Cruz, Victor,Notario, Rafael,Blair, Silvia,Echeverri, Fernando
, p. 3356 - 3378 (2013/05/22)
Solanum nudum Dunal steroids have been reported as being antimalarial compounds; however, their concentration in plants is low, meaning that the species could be threatened by over-harvesting for this purpose. Swern oxidation was used for hemisynthesis of diosgenone (one of the most active steroidal sapogenin diosgenin compounds). Eighteen structural analogues were prepared; three of them were found to be more active than diosgenone (IC50 27.9 μM vs. 10.1 μM, 2.9 μM and 11.3 μM). The presence of a 4-en-3-one grouping in the A-ring of the compounds seems to be indispensable for antiplasmodial activity; progesterone (having the same functional group in the steroid A-ring) has also displayed antiplasmodial activity. Quantitative correlations between molecular structure and bioactivity were thus explored in diosgenone and several derivatives using well-established 3D-QSAR techniques. The models showed that combining electrostatic (70%) and steric (30%) fields can explain most variance regarding compound activity. Malarial parasitemia in mice became reduced by oral administration of two diosgenone derivatives.
Further study on synthesis and evaluation of 3,16,20-polyoxygenated steroids of marine origin and their analogs as potent cytotoxic agents
Bunyathaworn, Potjamarn,Boonananwong, Suthinee,Kongkathip, Boonsong,Kongkathip, Ngampong
experimental part, p. 432 - 444 (2010/06/13)
A series of new polyoxygenated steroid derivatives with various steroid skeleton moieties were synthesized. Antitumor activity of the compounds against three tumor cell lines (Breast cancer MCF7, lung cancer NCI and oral cancer KB) were evaluated. Compoun
