Green synthesis of bile acids derivatives and 5β-cholanic acid was achieved under microwave irradiation, and the binding affinity for the ligand binding domain of the glucocorticoid receptor was measured.

Human aldo‐keto reductase 1C isoforms (AKR1C1‐C4) catalyze reduction of endogenous and exogenous compounds, including therapeutic drugs, and are associated with chemotherapy resistance. AKR1C2 is involved in metastatic processes and is a target for the treatment of various cancers. Here we used molecular docking to explore the potential of a series of eleven bile acid methyl esters as AKR1C2 inhibitors. Autodock 4.2 ranked 10 of the 11 test compounds above a decoy set generated based on ursodeoxycholic acid, a known AKR1C2 inhibitor, while 5 of these 10 ranked above 94 % of decoys in Autodock Vina. Seven inactives reported in the literature not to inhibit AKR1C2 ranked below the decoy threshold: 5 of these are specific inhibitors of AKR1C3, a related isoform. Using the same parameters, Autodock Vina identified steroidal analogs of AKR1C substrates, bile acids, and AKR1C inhibitors in the top 5 % of a virtual screen of a natural product library. In experimental assays, 6 out of 11 of the tested bile acid methyl esters inhibited >50 % of AKR1C2 activity, while 2 compounds were strong AKR1C3 inhibitors. Potential off‐target interactions with the glucocorticoid receptor were measured using a yeast‐based fluorescence assay, where results suggest that the methyl ester could interfere with binding. The top ranking compound based on docking and experimental results showed dose‐dependent inhibition of AKR1C2 with an IC50 of ∼3.6 μM. Molecular dynamics simulations (20 ns) were used to explore potential interactions between a bile acid methyl ester and residues in the AKR1C2 active site. Our molecular docking results identify AKR1C2 as a target for bile acid methyl esters, which combined with virtual screening results could provide new directions for researchers interested in synthesis of AKR1C inhibitors.

Naphthenic acids were isolated from gas oil fractions (distillation interval 168-290 qC) of Vojvodina crude oil "Velebit", characterized and their biological activity evaluated by the biochemical changes in cuttings of Robinia pseudoacacia after treatment with naphthenate. The activities of IAA peroxidase, total peroxidases and amylase, as well as the contents of reducing sugars and total proteins, were determined in the basal parts of soft wood cuttings of black locust after treatment with sodium naphthenate or the sodium salt of 1-naphthaleneacetic acid (NAA), concentration 10 -7 mol dm -3 for 3 or 6 h. High activities of IAA oxidase and amylase, together with a low activity of peroxidase (which is known as being stimulatory for the initiation and activation of primordia) were obtained after the three-hour treatment with sodium naphthenate. Six-hour treatment had an inhibitory effect on the examined biochemical markers. The effects of three-and six-hour treatments with NAA were between those of the corresponding treatment with naphthenic acids.

Naphthenic acids (NAs) are complex mixtures of cycloaliphatic and alkyl-substituted acyclic carboxylic acids whose overall characteristics are determined by the composition of the mixture. A complex mixture of NAs from a commercial fraction of atmospheric oil of the Vojvodina naphthenic crude "Velebit" (Serbia) was separated into narrower fractions on the basis of their acidity. Electrospray ionization mass spectrometry analysis of the fractions showed the occurrence of structural differentiation of acids. By extraction at pH 3-5, about 50% of the total mass of acids was separated, consisting predominantly of tricyclic and bicyclic structures. Acids of lower acidity, (about 22%), separated at pH 9 and 10, and their dominant constituents were acids with three, four and five rings. A correlation was found between the dominant structure and the biological activity of NAs of the fractions. The fraction extracted at pH 8, also with dominant bicyclic and tricyclic structures, showed the highest auxin and gibberellin activities

The synthesis of esters of natural petroleum acids of the naphthenic type assisted with microwave irradiation under the conditions of acid catalysis was carried out with various alcohols: methanol, ethanol, n-butanol and tert-butyl alcohol. Microwave dielectric heating of the reaction mixture in an unmodified microwave oven with activation of the naphthenic acids with sulfuric and p-toluenesulfonic acid afforded the esters of the naphthenic acids. Depending on the catalyst and the steric and nucleophilic properties of the alcohols, the yield of naphthenic esters ranged from 31.25% to 88.90%. As a consequence of microwave dielectric heating, the esterification time was reduced from 6-10 h to 5 min. .