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Salmonella is a Gram-negative bacterium that causes gastrointestinal diseases in 20 to 40 million people globally. Stemmoside C is a steroidal glycoside isolated from Argel, although its antibacterial and antibiofilm properties have not been studied. The antibacterial activity of Stemmoside C against Salmonella enterica was revealed, where MIC of the compound was 16 μg/mL (0.15 µM). Biofilm-associated Stemmoside C treatment destroyed S. typhi cells and reduced viable S. typhi numbers below detectable levels. When compared to Stemmoside C or Ciprofluxacin-treated mice, infected BALB/c mice had a greater death rate and a larger bacterial blood burden. The protective effects of orally administered Stemmoside C at dose of 25 and 50 mg/kg b.wt. against bacterial infection was associated with reduction in the levels of inflammatory cytokines (IFN-γ, Il-1β, IL-2, IL-6, MPO, and TNF-α) and elevation of anti-inflammatory cytokine (IL-10 and IL-12) in serum. Where, Stemmoside C at dose of 50 mg/kg b.wt. regulated the levels almost as normal control group and demonstrated apparently normal intestinal sections. It also resulted in a decrease in the number of viable S. typhi retrieved from feces. Stemmoside C is a promising drug for the treatment or prevention of S. typhimurium infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A preliminary chemical investigation on 70% MeOH extract of the roots of Asparagus cochinchinensis resulted in the isolation of nine steroids. These isolates comprised of four new C 21 (1-4) and one new pregnane (5) glycosides, and four known C 27 (6-9) spirostanol steroids. Their structures were identified via analysis of the spectroscopic data and the results of hydrolytic cleavage. The cytotoxic activities of the compounds were tested toward the human tumor cell line Hela (cervical cancer), and compounds 7 and 8 displayed moderate activity with IC 50 values of 35.5 and 39.6 μM, respectively., (Copyright © 2021. Published by Elsevier Inc.)

Gastric ulcers are a very common public health problem affecting up to 10% worldwide. Russelioside B is a steroidal glycoside isolated from several Caralluma species. No study tested the ulcer healing potential of the compound. The current study aimed to assess the protective effect of russelioside B against ethanol-induced gastric mucosal injury in rats. Ulcer was induced on rats by a single intragastric dose of absolute ethanol (5 mL/kg). Rats were randomly assorted into four groups (n = 8) and given treatments (Antodine, 20 mg/kg or russelioside B, 50 mg/kg) by oral gavage 1 h before ulcer induction. Pretreatment with russelioside B (50 mg/kg) attenuated the gastric mucosal injury as proved by a decrease of ulcer index, and histological scores. It suppressed the gastric inflammation by a significant lowering the tumor necrosis factor-α and interleukin-6 levels with myeloperoxidase activity (which are also aggravating factors in the case of Covid-19 infection). In addition, administration of russelioside B halted the gastric oxidative stress via inhibition of lipid peroxides by maintaining reduced glutathione and by decreasing malondialdehyde. It was able also to restore the sharp drop in the levels of heat shock protein-70, vascular endothelial growth factor and prostaglandin E2 induced by ethanol. Additionally, it showed carbonic anhydrase inhibition activity. The gastroprotective action of russelioside B was umpired through multi mechanistic actions; suppression of gastric oxidative stress, inflammation, anti-apoptotic activities and enhanced gastric mucosal protection by up-regulation of endothelial growth factor, normalization of heat shock protein-70 and prostaglandin E2. These actions were comparable in part to some classical antiulcer drugs such as Antodine., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Five new pregnane-type steroidal glycosides, named menarandrosides A-E (1-2, 5-7) were isolated from the aerial parts of Cynanchum menarandrense, together with three known compounds, carumbelloside I (3), carumbelloside II (4), and pregnenolone-3-O-gentiobioside (8). Their structures were determined on the basis of spectroscopic analyses including NMR and mass spectrometry, reporting C-21 steroids glycosylated only by one or two glucose moieties. Compounds were then investigated for their potential to stimulate glucagon-like peptide-1 (GLP-1) secretion in intestinal cells; although none of the pure compounds had any influence, the fraction enriched in pregnanes exhibited a significant activity, suggesting a possible synergistic effect. Furthermore, none of the purified compounds affected cell viability., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Five new pregnane-type steroids namely subergorgols T-X (1-5) and three known analogues (6-8) were isolated from a gorgonian coral Subergorgia suberosa. The structures of new compounds were determined on the basis of extensive spectroscopic (IR, MS, 1D and 2D NMR) data analyses, in association with photochemical transformation and ECD methods for the configurational assignment. Compounds 1-8 were evaluated for the inhibitory effects against H1N1 virus infected in MDCK cells, while subergorgols T-U and 1,2-dehydroprogesterone exerted potent inhibition against A/WSN/33 virus., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Fourteen new pregnane glycosides, including nine caudatin glycosides (1-9), three qinyangshengenin glycosides (10-12), one kidjoranin glycosides (13) and one gagaminin glycosides (14), along with twelve known analogs (15-26) were isolated from roots of Cynanchum otophyllum Schneid. Their structures were deduced by detailed analysis of 1D and 2D NMR spectra, as well as HRESIMS. In this study, all pregnane glycosides obtained (1-26) were evaluated for their cytotoxic activities using three cancer cell lines (HepG2, Hela, U251). As results, except 6 and 10, other twenty-four pregnane glycosides showed cytotoxicities at different degrees against three cell lines., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Fourteen novel 14,15-diseco-18-nor-pregnane-type steroidal glycosides, mooreanoside A-C (1-3) and mooreanoside F-P (6-16) and two new 14,15-diseco-pregnane-type steroidal glycosides, mooreanoside D-E (4-5) were isolated from the roots of Cynanchum mooreanum Hemsl. Their structures were determined on the basis of spectroscopic and chemical analysis. Compounds 1-6, 8-10, 12-14 and 16 were tested for their immunological activities in vitro against Con-A induced proliferation of mice splenocytes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

As a part of our continuing interest in identifying anticancer drug leads from natural sources, we have investigated the n-BuOH fraction of the root bark of Calotropis procera (Ait) R. Br. Seven new oxypregnane oligoglycosides: calotroposides H-N (1-7) were isolated and identified. Their structures were established on the basis of 1D and 2D NMR studies, HRMS, and GCMS spectral data. The in vitro growth inhibitory activity of the n-BuOH fraction and compounds 1-7 was evaluated against A549 non-small cell lung cancer (NSCLC), U373 glioblastoma (GBM), and PC-3 prostate cancer cell lines. Compounds 4 and 6 showed subnanomolar growth inhibition activity with IC50 ranging from 0.5 to 0.7μM against U373 glioblastoma (GBM) and PC-3 prostate cancer cell lines. These results provide further insight into the chemical diversity and biological activities of this class of compounds., (Copyright © 2015 Elsevier Inc. All rights reserved.)

New oxazolinyl derivatives of [17(20)E]-pregna-5,17(20)-diene: 2'-{[(E)-3β-hydroxyandrost-5-en-17-ylidene]methyl}-4',5'-dihydro-1',3'-oxazole 1 and 2'-{[(E)-3β-hydroxyandrost-5-en-17-ylidene]methyl}-4',4'-dimethyl-4',5'-dihydro-1',3'-oxazole 2 were evaluated as potential CYP17A1 inhibitors in comparison with 17-(pyridin-3-yl)androsta-5,16-dien-3β-ol 3 (abiraterone). Differential absorption spectra of human recombinant CYP17A1 in the presence of compound 1 (λmax=422 nm, λmin=386 nm) and compound 2 (λmax=416 nm) indicated significant differences in enzyme/inhibitors complexes. CYP17A1 activity was measured using electrochemical methods. Inhibitory activity of compound 1 was comparable with abiraterone 3 (IC50=0.9±0.1 μM, and IC50=1.3±0.1 μM, for compounds 1 and 3, respectively), while compound 2 was found to be weaker inhibitor (IC50=13±1 μM). Docking of aforementioned compounds to CYP17A1 revealed that steroid fragments of compound 1 and abiraterone 3 occupied close positions; oxazoline cycle of compound 1 was coordinated with heme iron similarly to pyridine cycle of abiraterone 3. Configuration of substituents at 17(20) double bond in preferred docked position corresponded to Z-isomers of compounds 1 and 2. Presence of 4'-substituents in oxazoline ring of compound 2 prevents coordination of oxazoline nitrogen with heme iron and worsens its docking score in comparison with compound 1. These data indicate that oxazolinyl derivative of [17(20)E]-pregna-5,17(20)-diene 1 (rather than 4',4'-dimethyl derivative 2) may be considered as potential CYP17A1 inhibitor and template for development of new compounds affecting growth and proliferation of prostate cancer cells., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Two new unusual cholestane derivatives, pentacyclic steroid 16,22-epoxy-20β,23S-dihydroxycholest-1-ene-3-one (1) and 20β,23S-dihydroxycholest-1-ene-3,22-dione (2), along with two new pregnane derivatives, 15β,17α-dihydroxypregna-4,6-diene-3,20-dione (3) and 11α-hydroxypregna-4-ene-3,6,20-trione (4), were isolated from the South China Sea gorgonian coral Subergorgia suberosa. Their structures were established based on the extensive analyses of 2D NMR, IR, and HRMS. Antifouling tests against Balanus amphitrite larvae settlement indicated that 1 and 2 exhibited inhibitory effect with EC50 values of 5.3, and 14.5 μg/mL, respectively., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Five new polyhydroxypregnane glycosides, namely cynanotosides A-E (1-5), together with two known analogues, deacetylmetaplexigenin (6) and cynotophylloside H (7), were isolated from the roots of Cynanchum otophyllum. Their structures were established by spectroscopic methods and acid hydrolysis. The neuroprotective effects of compounds 1-7 against glutamate-, hydrogen peroxide-, and homocysteic acid (HCA)-induced cell death were tested by MTT assay in a hippocampal neuronal cell line HT22. Compounds 1, 2, and 7 exhibited protective activity against HCA-induced cell death in a dose-dependent manner ranging from 1 to 30μM, which may explain the Traditional Chinese Medicine (TCM) use of this plant for the treatment of epilepsy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Nine new steroidal glycosides, named as stauntosides C-K (2, 5, 7-10, 13, 14, and 16), along with seven known compounds (1, 3, 4, 6, 11, 12, and 15) were isolated from the 95% ethanol extract of the roots of Cynanchum stauntonii. The structures of these new compounds were elucidated on the basis of extensive spectroscopic analyses, mainly 1D and 2D NMR, and HRESI-MS, and qualitative chemical methods. Their significance in terms of the chemotaxonomy of C. stauntonii is discussed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

19-Hydroxy-6-azapregnanes were obtained from pregnenolone via a 7-azido-5-oxo-6-nor-5,7-secopregnane intermediate. The 6-azapregnane core was built in good yield in a straightforward way from the secosteroid, by means of a Staudinger (aza-Wittig) reaction. Finally the 19-hydroxy-6-azapregnane was transformed into 19-hydroxy-6-azaprogesterone (that cyclized spontaneously to the 19→3 hemiketal) and 6-azaprogesterone. The 6-azapregnanes lacked agonistic/antagonistic activity on the progesterone receptor., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The steroid nucleus is an interesting scaffold for the development of new therapeutic agents. Within the goal of identifying anticancer agents, new pregnane derivatives were prepared by using a sequence of liquid and solid-phase reactions. After we dehydrated epi-allopregnanolone in one step with diethylaminosulfur trifluoride and generated a 2,3α-epoxide, the regio- and stereo-selective aminolysis of this epoxide enabled us to obtain a 2β-piperazino-pregnane, whose secondary amine was protected as N-Fmoc-derivative. Using the difference in reactivity between OHs 3 and 20, we linked the pregnane nucleus-selectively on the polystyrene diethylbutylsilane resin via the OH in position 20. We next achieved in parallel the coupling of an amino acid (1st level of diversity) and the coupling of a carboxylic acid (2nd level of diversity) to generate two libraries of pregnane derivatives. The compounds inhibited the HL-60 leukemia cell growth and the most potent were three compounds (PD, LPC-37 and LPC-48) with a l-proline as first level of diversity and a cyclohexyl-carbonyl, a naphthalene-2-carbonyl or a 3-acetylbenzoyl as second level of diversity. LPC-48 efficiently inhibited HL-60 cell proliferation with IC(50) value of 1.9 μM and exhibited a low toxicity on normal peripheral blood lymphocytes (IC(50)=31 μM). These results encouraged us to further evaluate the biological activity of these new aminosteroids by investigating their preliminary mechanism of action., (Copyright © 2012 Elsevier Inc. All rights reserved.)

One novel uncommon steroid, ximaosteroid A (1), possessing an unusual tetrahydrofuran moiety and three new pregnane steroids, ximaosteroids B-D (2-4), were isolated from the Hainan soft coral Scleronephthya sp. Their structures were elucidated on the basis of detailed spectroscopic (IR, MS, and 2D NMR) analysis and by comparison with those reported in the literature.

The present study is addressed to ascertain the inhibitory effect of several progesterone derivatives having a chlorine substituent at C-6 (12a-12d), 15 with a bromine substituent at C-6 and 14a-14d, without any halogen atom at C-6 all having an ester side chain at C-17 (benzoate ester bearing a Cl, F and a Br atom at C-4 position of the phenyl ring) on the 5alpha-reductase enzyme activity present in human prostate. In addition, it was also of interest to investigate the pharmacological effect on hamster flank organs diameter size. In order to study the structure-activity relationships of steroids 12a-12d, 14a-14d and 15 we determined the concentration of these steroids that inhibited 50% of the activity of human prostate 5alpha-reductase enzyme (IC(50)), as well as the in vivo effect of these compounds in the hamster flank organs diameter size. We also ascertained, the capacity of these steroids to bind to the androgen receptors present in the rat prostate cytosol using labeled mibolerone (MIB) for monitoring the binding to the androgen receptor. The results from this study indicated that compounds 12a-12d (having a chlorine substituent at C-6), 14a-14d (lacking a halogen atom at C-6), 13 and 15 (having a bromine atom at C-6) showed an increased antiandrogenic effect (lower value for the diameter of the flank organs) as compared to the flank organs from testosterone-treated hamsters. On the other hand, the series of compounds containing a chlorine substituent at C-6 compounds (12a-12d) showed a higher antiandrogenic activity as compared to the compounds lacking a halogen atom at C-6 (14a, 14b and 14d). Although compounds 13 and 15 decreased the flank organs diameter size, however, this increase was not statistically significant as compared to that of the commercially available product finasteride. The steroidal derivatives 13, 14a-14d (lacking the chlorine substituent at C-6) and 15 (having a bromine atom at C-6) exhibited a higher 5alpha-reductase inhibitory activity (lower IC(50) values) as compared to the series of compounds 12a-12d having the halogen substituent at C-6. Finasteride reduced the diameter size of the flank organs. The effect of this steroid and compounds 12a-12d, 13, 14a-14d and 15 on hamster flank organs can be explained by the fact that these steroids did not bind to the androgens receptor, which indicates that its mechanism of action is an inhibiting for the 5alpha-reductase activity. This enzyme is present in the hamster flank organs and was inhibited by the novel steroids in the human prostate homogenates.

The synthesis of several novel 5alpha- and 5beta-20-oxo-pregnane derivatives substituted in the position 3 and 7 of the steroid skeleton is described. Activity of synthesized compounds was studied in voltage-clamped cultured rat hippocampal neurons. Substituted derivatives inhibited NMDA-elicited neuronal activity. The relationship between biological activity and structure is discussed.

Five new pregnane glycosides, cynanosides K-O (1-5) with a 14,15-seco-pregnane-type skeleton as the aglycon, together with five known compounds, cynascyroside C, sublanceoside E(1), sublanceoside I(1), atratoside A and atratoside B, were isolated from the roots of Cynanchum atratum. Their structures were determined on the basis of spectroscopic analysis and chemical evidence.

Seven new 15-keto pregnane glycosides, namely Stemmosides E--K, were isolated from Solenostemma argel. Stemmosides E--J are characterized by the occurrence of an uncommon 14 beta proton configuration while stemmosides E and F possess in addition a rare enolic function in C-16. On the other hand, stemmosides G-J display an unusual C-17 alpha side chain. Their structures were established by ESI-MS and NMR experiments. Moreover, the effect of these compounds on the VEGF-induced in Kaposi's sarcoma cell proliferation was tested. Results indicated that all the compounds reduced the cell proliferation in a dose dependent manner.

Twenty-seven new pregnane glycosides were isolated from the whole plant of Caralluma dalzielii, and their structures elucidated from extensive 2D NMR analysis as well as ESI-MS experiments. All isolated compounds were tested for their antiproliferative activity on J774.A1, HEK-293, and WEHI-164 cell lines. Moderate to high potency of cytotoxicities were found in almost all tested compounds, confirming the significant cytotoxic activity of pregnane glycosides.

The pharmacological activities of four pregnane derivatives: 17alpha-hydroxy-16beta-methylpregna-4,6-diene-3,20-dio ne (7), 17alpha-acetoxy-16beta-methylpregna-4,6-diene-3,20-dio ne (8), 17alpha-acetoxy-6-bromo-16beta-methylpregna-4,6-diene- 3,20-dione (10), and 17alpha-acetoxy-6-chloro-16beta-methylpregna-4,6-diene -3,20-dione (11), were determined. The derivatives were evaluated on gonadectomized male hamster flank organs and seminal vesicles. The results indicate that topical applications of testosterone (T) on the flank organs increased the diameter of the pigmented spot. Similarly, the same phenomenon occurred on the glands treated with compound 11, whereas compound 10 decreased the size of the spot significantly. In this study, we determined the effects of several new steroids on the conversion of T to DHT in flank organs and seminal vesicles. The results show that compound 10 inhibited T conversion to DHT, but compound 11, at a dose of 200 microg, stimulated T conversion in both flank organs and seminal vesicles. However, when 2 mg of compound 11 was applied, it inhibited the conversion of T to DHT, suggesting that this compound also represses gonadotropin release. The difference between compounds 10 and 11 involves the electronegativity of the halogen at the C-6 position of the progesterone skeleton. These data clearly indicate that by decreasing the electronegativity of the halogen at C-6 (compound 10), 5alpha-reductase is inhibited in both tissues and at different pHs. On the other hand, when the electronegativity of the halogen atom was increased (11), there was a much lower inhibitory effect on the conversion of T to DHT.

A blinded cooperative assay of several androstane and pregnane steroid metabolites has been carried out in order to determine whether 5beta-H derivatives are as active as testosterone in stimulating in vivo erythropoiesis. The steroids tested were: testosterone, 5alpha-dihydrotestosterone, 5beta-dihydrotestosterone, 5beta-pregnane-3,20-dione, 3alpha-dihydroxy-5beta-pregnane-11,20-dione and 3beta-hydroxy-5beta-pregnan-20-one. The incorporation of radioactive iron into newly formed red cells in exhypoxic polycythemic mice was used to compare the effects of the steroids. Testosterone and 5alpha-dihydrotestosterone both produced significant increases in 59Fe incorporation. 5beta-dihydrotestosterone, 5beta-pregnane-3,20-dione, 3alpha-hydroxy-5beta-pregnane-11,20-dione and 3beta-hydroxy-5beta-pregnan-20-one were all devoid of significant erythropoietic activity in polycythemic mice in almost all instances. Thus, under the conditions chosen, this study failed to demonstrate that 5beta-steroids increase radioactive iron incorporation in red cells of exhypoxic polycythemic mice.

Ten natural progestins were evaluated for their capacity to inhibit the in vitro motility of rat's uterus. Progestins with their ring A reduced in the 5 beta position were significantly more potent than delta 4-3 keto and 5 alpha reduced progestins. These last progestins were ineffective to inhibit uterine motility excepting 3 alpha-hydroxy-5 alpha-pregnan-20-one which was slightly less effective than progesterone. The potency of the progestins to inhibit uterine motility was related to their capacity to induce membrane stabilization. The data indicates that 5 beta, but not 5 alpha reduction of progesterone, may be important for regulating myometrial activity.