The opportunities provided by biotechnology and phytoengineering methods for producing physiologically active substances (secondary metabolites) of plant origin are considered. It is noted that ...alkaloids, flavonoids, terpenes, steroids, and other compounds of plant origin are of pharmaceutical interest and can be prepared using cellular technologies and plant cell and tissue culture.
Urolithin A is a polyphenolic metabolite of ellagic acid and ellagitannins that is produced by the intestinal microbiota and has a higher bioavailability than the parent polyphenols. The ability of ...urolithin A to suppress the production of various cytokines by tumor cell lines HeLa (cervical adenocarcinoma), HT1080 (fibrosarcoma), K562 (chronic myelogenous leukemia), and Jurkat (T-lymphoblastic leukemia) was studied in the present work. Urolithin A significantly (by ~2 times) suppressed basal production of GRO, IL-6, IP-10 (CXCL10), and MCP-1 (CCL2) by HeLa cancer cell line. Urolithin A also suppressed production of IL-8 by K562 cell line and of PDGF-AA by Jurkat cells. A trend for urolithin A to suppress VEGF production by HT1080 cancer cell line may also exist. Urolithin Acan suppress the production of various inflammatory factors by tumor cells, thereby reducing chronic inflammation and having the potential to reduce tumor-induced immunosuppression.
Current Trends in Steroid Chemistry Sokolov, M. N.; Rozhkov, V. V.; Trukhan, V. M. ...
Pharmaceutical chemistry journal,
06/2023, Letnik:
57, Številka:
3
Journal Article
Recenzirano
Literature data over the past 10 years on the search for new drugs based on synthetic steroids are summarized and reviewed. Modern achievements in improving the effectiveness of steroid compounds are ...described. Methods for improving and modulating their pharmacological profile and biological activity are considered. The main attention is paid to the dependence of biological activity on chemical modification of the steroid scaffold or side chains. The role of compounds containing a steroid scaffold in the therapy of hormone-dependent tumors is highlighted.
A compound with low toxicity and pronounced antidepressant activity upon single and long-term administration was discovered by us earlier among a series of new thietanylxanthine derivatives. The ...present article focused on the central mechanisms of action of 2-3-methyl-7-(thietan-3-yl)-1-ethylxanth-7-ylthioacetic acid hydrazide (laboratory code M-20). Neuropharmacological analysis showed that M-20 at doses of 0.97 and 12 mg/kg exhibited effects indicative of possible stimulatory action on adrenergic and inhibitory action on GABA-ergic neurotransmission in brains of outbred white mice. M-20 at a dose of 12 mg/kg produced an activating effect on the serotoninergic system in addition to action on the adrenergic and GABA-ergic systems and altered the activity of the cholinergic system. M-20 at doses of 0.97 and 12 mg/kg did not alter the effects of haloperidol and L-DOPA, which indicated that it did not influence dopaminergic neurotransmission and MAO-inhibiting activity. The results indicated that M-20 was promising (at the low dose) for use with depression associated with decreased activity of the serotoninergic system without side effects on the dopaminergic and cholinergic systems.
The modern clinical oncology key task is to increase the efficiency of anticancer chemical therapy. The main direction of provided investigations are to ensure targeted delivery of drugs to cancer ...cells with the minimization of the harmful effect to normal cells, as well as overcoming the multiple drug resistance of cancer cells. One of the possible solutions is to use nanoporous medium filled with non-wetting liquid (drug) as a carrier. Interest to such systems is caused by two effects observed for such systems: the effect of non-wetting liquid dispersion in pores and it's anomalously slow relaxation (outflow). It has also been shown that these effects are critically dependent on temperature. The work is present results of experimental study of the kinetics of model liquid outflow from nanoporous medium at the temperature range 20-40 °C. Results obtained for systems with different granule sizes and surface modifications.
Urolithin A is a polyphenolic metabolite of ellagic acid and ellagitannins that is produced by intestinal microbiota and has higher bioavailability than the parent polyphenols. Regarding acute ...inflammation modeling, urolithin A(5 μM) and a combination of urolithin Awith cholecalciferol (0.01 μM) were shown to reduce phytohemagglutinin-stimulated production of IFN-γ by peripheral blood mononuclear cells (PBMC) of healthy donors (by 19 and 27%, respectively). The ability of the growth medium obtained from cancer cell cultivation to reduce IFN-γ production by PBMC was used by us to evaluate the effect of urolithin A on the immunosuppressive effect of chronic inflammation. Addition to HeLa tumor cells (cervical adenocarcinoma) of urolithin A, which suppresses production of various immunoregulatory factors by tumor cells, reduced the ability of the medium in which the tumor cells were cultivated to suppress IFN-γ production by PBMC. Thus, it can be assumed that urolithin Adecreases the immunosuppressive potential of the tumor microenvironment.
Primary glucocorticoid resistance (OMIM 615962) is a rare endocrinologic condition caused by resistance of the human glucocorticoid receptor (hGR) to glucocorticoids (GR) and characterised by general ...or partial insensitivity of target organs to GK. Compensatory activation of hypothalamic-pituitary-andrenal axis results in development of a various pathological conditions caused by overstimulation of adrenal glands. Clinical spectrum may range from asymptomatic cases to severe cases of mineralocorticoid and/or androgen excess. At present time, primary generalized glucocorticoid resistance has been exclusively associated with defects in the NR3C1 gene. Here, we present a case report of an adolescent patient with clinical presentation of glucocorticoid resistance confirmed by detailed endocrinologic evaluation but no confirmed mutations in the NR3C1 gene.
Scanning probe microscopy is used to study the effect of cytotoxic agents on the biomechanical and physicochemical properties of tumor cells and tissues. The possibility of using quantitative data of ...atomic force and capillary microscopy in assessing the morphological characteristics of cells during carcinogenesis is considered. The prospects of using morphometric analysis in biomedicine, biomechanics, regenerative medicine, and drug testing are described. The roughness of the control sample of HeLa human cervical cancer cells in terms of the average (Ra) and root-mean-square values (Rq) was 35 ± 5/48 ± 6 nm upon subtraction of a spline and 33 ± 5/45 ± 6 nm upon subtraction of a parabola, respectively. The roughness remains almost the same under the impact of cisplatin whereas nocodazole significantly increases the roughness to 51 ± 5/68 ± 6 nm and 56 ± 6/72 ± 7 nm, respectively.
With the aim of clarifying the cytostatic effect of the Russian-made gestagen gestobutanoil (17α-acetoxy-3β-hydroxy-6-methylpregna-4,6-dien-20-one butyl ester), which is a member of an original group ...of transformed gestagens containing an ester substituent in place of the 3-keto group, the cytostatic activities of its metabolites (17α-acetoxy-3β-hydroxy-6-methylpregna-4,6-dien-20-one (AMP-17) and megestrol acetate) and a reference agent (progesterone) were studied in uterine cervical tumor line HeLa. Complex formation by these steroids with progesterone receptor binding sites was evaluated by computer modeling (docking) by determination of the interaction energy of the partner molecules. The cytostatic activity of gestobutanoil was greater than that of reference compound and may be associated with the formation of its active metabolites. Conformations of the gestobutanoil-receptor complex with binding energies significantly different from those of complexes with progesterone, AMP-17, and megestrol acetate were demonstrated; this may be the cause of changes in the affinity of gestobutanoil for progesterone receptors and modulation of its biological activity.
New mepregenol 17-acetate derivatives with potential cytotoxicity were synthesized. Mepregenol 17-acetate 3-acrylate (
III
) was shown to exhibit potent cytotoxicity although the ester of
N
...-benzylpyrrolidine-3-carboxylic acid (
IV
) had weaker activity that was comparable with those of megestrol acetate and progesterone. The IC
50
values for
III
,
IV
, progesterone, and megestrol acetate were 30, 200, 480, and 130 μMwith respect to native HeLa culture and 9.1, 180, 5.6, and 115 μm for an estradiol-stimulated culture of HeLa, respectively. The cytotoxicities of steroids
III
and
IV
correlated with their DNA-damaging effect in a DNA comet assay. Thus,
III
was promising for further research as an antitumor compound with respect to estradiol-dependent tumors.
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