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Dehydroepiandrosterone (DHEA) is an important neurosteroid hormone to keep human hormonal balance and reproductive health. However, DHEA was always produced with impurities either by chemical or biological method and required high-cost purification before the medical use. To address this issue, a novel chemoenzymatic process was proposed and implemented to produce DHEA. An acetoxylated derivate of 4-androstene-3,17-dione (4-AD) was generated by chemical reaction and converted into DHEA by an enzyme cascade reaction combining a hydrolysis reaction with a reduction reaction. The hydrolysis reaction was catalyzed by a commercial esterase Z03 while the reduction reaction was catalyzed by E. coli cells co-expressing a 3β-hydroxysteroid dehydrogenase SfSDR and a glucose dehydrogenase BtGDH. After the condition optimization, DHEA was synthesized at a 100 mL scale under 100 mM of substrate loading and purified as white powder with the highest space-time yield (4.80 g/L/h) and purity (99 %) in the biosynthesis of DHEA. The successful attempt in this study provides a new approach for green synthesis of highly purified DHEA in the pharmaceutical industry., 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.)

Chagas disease is a health problem that affects millions of persons, currently Nifurtimox (Nfx) and Benznidazole (Bz) are the unique drugs to treat it. However, these drugs produce adverse effects and high toxicity, which has motivated the search for new candidate drugs. Based on reports about the extensive biological activity of steroidal nitrate esters, in this study three nitrate esters steroids (1b, 2b and 4b) were synthetized and characterized from Dehydroepiandrosterone (DHEA, 1a), 19-hydroxy-DHEA (2a), and Androst-5-en-3β,17β-diol (4a), respectively. In addition, compounds 3a and 3b were obtained by introducing an α-ethynyl and a β-hydroxyl groups at position 17 of 2b and further nitration of the hydroxyl group. The trypanocidal activity of these steroids was evaluated in vitro against the epimastigote stage of two T. cruzi strains, Ninoa and TH, and their cytotoxicity over J774.2 macrophage cell line was assayed. Compounds 3a, 3b, and 4a shown higher trypanocidal activity than Bz and Nfx against epimastigotes of Ninoa strain, whereas DHEA (1a) and its nitrate derivative 1b showed higher activity than the reference drugs against the TH strain epimastigote. None of the compounds showed activity in the ex vivo assays against the blood trypomastigote of both strains. Interestingly, the selectivity index of Androst-5-en-3β,17β-diol 4a was almost twice the value of Nfx and 50 times more than Bz, against Ninoa and TH strains, respectively. Therefore, compound 4a could represent a valuable starting point toward the optimization of steroid derivatives as trypanocidal agents., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Hybrid molecules consisting of steroid-imidazolium salts reveal interesting biological properties, especially regarding antimicrobial activities. Novel dehydroepiandrosterone derived imidazolium salts (11 salts) with side chains of different lengths were obtained in an efficient and straightforward synthetic route. Antimicrobial properties of new salts were examined by determining their minimum inhibitory concentrations (MICs). They were studied against several strains of bacteria, including clinical isolates of MRSA, and fungi. New compounds showed high activity against Gram-positive bacteria and Candida albicans as well as good compatibility with the representatives of the host cells when applied at concentrations corresponding to MIC value. The studies indicated high antimicrobial efficacy of imidazolium salts against the above-mentioned microorganisms with low hemolytic activity at a concentration that restricts the growth of the microorganisms. The interference of salts with the immune defense system, the influence on the biological activity of monocytes/macrophages measured by their viability and metabolic activity was also studied. The new compounds have shown immunoprotective properties., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A series of steroidal[17,16-d]pyrimidines derived from dehydroepiandrosterone were designed and prepared by a convenient heterocyclization reaction. The in vitro anticancer activities for these obtained compounds were evaluated against human cancer cell lines (HepG2, Huh-7, and SGC-7901), which demonstrated that some of these heterocyclic pyrimidine derivatives exhibited significantly good cytotoxic activities against all tested cell lines compared with 5-fluorouracil (5-FU), especially, compound 3b exhibited high potential growth inhibitory activities against all tested cell lines with the IC 50 values of 5.41 ± 1.34, 5.65 ± 1.02 and 10.64 ± 1.49 μM, respectively, which might be used as promising lead scaffold for discovery of novel anticancer agents.

5α-R isozymes (types 1 and 2) play an important role in prostate gland development because they are responsible for intraprostatic dihydrotestosterone (DHT) levels when the physiological serum testosterone (T) concentration is low. In this study, we synthesized seven novel dehydroepiandrosterone derivatives with benzimidazol moiety at C-17, and determined their effect on the activity of 5α-reductase types 1 and 2. The derivatives with an aliphatic ester at C-3 of the dehydroepiandrosterone scaffold induced specific inhibition of 5α-R1 activity, whereas those with a cycloaliphatic ester (cyclopropyl, cyclobutyl, or cyclopentyl ring) or an alcohol group at C-3 inhibited the activity of both isozymes. Derivatives with a cyclohexyl or cycloheptyl ester at C-3 showed no inhibitory activity. In pharmacological experiments, derivatives with esters having an alcohol or the aliphatic group or one of the three smaller cycloaliphatic rings at C-3 decreased the diameter of male hamster flank organs, with the cyclobutyl and cyclopentyl esters exhibiting higher effect. With exception of the cyclobutyl and cyclopentyl esters, these compounds reduced the weight of the prostate and seminal vesicles.

A series of novel peptidomimetics bearing dehydroepiandrosterone moiety were designed, synthesized, and evaluated for their inhibition activities against cell proliferation. According to the preliminary studies on inhibitory activities, some of the newly prepared compounds indicated significantly inhibition activities against human hepatoma cancer (HepG2), human lung cancer (A549), human melanoma (A875) cell lines compared with the control 5-fluorouracil. Especially, compounds Ii (IC50 < 14 μM) and Ik (IC50 < 13 μM) exhibited obvious inhibition activities against all tested cell lines. The highly potential compound Ik induced apoptosis in HepG2 cells were analyzed by flow cytometry, and the apoptotic effects of compound Ik were further evaluated using Annexin V-FITC/propidium iodide dual staining assay, which revealed these highly potential compounds induced cell death in HepG2 cells at least partly by apoptosis.

7-Oxygenated metabolites of dehydroepiandrosterone (DHEA) are known for their neuroprotective and immunomodulatory properties. These neuroactive steroids are currently predominately analysed by mass spectrometry, for which the use of internal deuterated standards is necessary. The aim of this study was to synthesize the deuterated derivatives of 7α-hydroxy-DHEA and 7-oxo-DHEA and test them in liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to enhance the performance characteristics of this method. Here we report the synthesis of 3α deuterium-labelled 7α-hydroxy-DHEA and 7-oxo-DHEA. Deuterium was introduced into the 3α position by reduction of the corresponding 3-ketone with a protected 17-carbonyl group using NaBD4. Our new procedure allows the easier synthesis of deuterated steroid labelled compounds. The use of these deuterated steroids enabled us to improve the human plasma LC-MS/MS analysis of 7α-hydroxy-DHEA and 7-oxo-DHEA in terms of sensitivity, precision and recovery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

As an extension of previously conducted studies on developing an anti-Alzheimer's disease agent, denosomin (1-deoxy-24-norsominone, an artificial inducer of neurite elongation), derivatives were designed and synthesized based on the hypothesis that our denosomin would exhibit axonal extension activity via a 1,25D(3)-membrane-associated, rapid response steroid-binding protein (1,25D(3)-MARRS) pathway. The biological assay revealed that the hybridization of characteristic δ-lactone in denosomin and the triene moiety in VD(3) was effective to enhance the nerve re-extension activity in amyloid β (Aβ)-damaged neurons.