A natural brassinosteroid and a series of synthetic derivatives were found to be good inhibitors of herpes simplex virus type 1 (HSV-1) and arenavirus replication in cell culture. The synthetic compounds tested were analogues of the 24(S) ethylbrassinone. Compounds (22R,23R,24S)-2α, 3α,5α,22,23-pentahydroxy-stigmastan-6-one and (22R,23R,24S)-3β-bromo-5α,22,23-trihydroxy stigmastan-6-one were cytotoxic at concentrations of 20–40 µM. (22S,23S,24S)-2α,3α,22,23-tetrahydroxy-5α,stigmastan-6-one, (22R,23R,24S)-3β-acetoxy-22,23-dihydroxy-5α-cholestan-6-one, (22S,23S,24S)-3β-bromo-22,23-dihydroxy-5α-cholestan-6-one and (22S,23S,24S)-3β-bromo-5α,22,23-trihydroxy-stigmastan-6-one were the most active of the series against HSV-1, with selectivity index (SI) values (CC₅₀/EC₅₀) ranging from 10.6 to 16.5. The majority of the compounds were potent inhibitors of arenaviruses, (22S,23S,24S)-3β-bromo-5α,22,23-trihydroxy-stigmastan-6-one being the most active, with SI values of 307.8 and 692.5 for Tacaribe and Junin viruses, respectively. The antiviral activity of brassinosteroid derivatives was not because of direct inactivation; time-of-addition experiments suggested that a late step in HSV-1 multiplication was affected, whereas arenaviruses remained susceptible to the compounds throughout the replicative cycle.

Twenty-seven brassinosteroid derivatives were tested for antiviral activity against measles virus (MV) via a virus-yield reduction assay. Compounds 6b [(22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one], 1d [(22R,23R)-2α,3α,22,23-tetrahydroxy-β-Homo-7-oxa-stigmastan-6-one], 8a [(22R,23R)-3β-fluoro-22,23-dihydroxystigmastan-6-one], 9b [(22S,23S)-3β-fluoro- 5α,22,23-trihydroxystigmastan-6-one] and 10b [(22S,23S)-5α-fluor-3β,22,23-trihydroxystigmastan-6-one], with selectivity indexes (SI) of 40, 57, 31, 37 and 53, are the derivatives with good antiviral activity against MV. These SI values are higher than those obtained with ribavirin (used as reference drug). A comparative analysis of 50% cytotoxic concentration (CC₅₀) values, using confluent non-growing cells, gives and indication of structure—activity relationship. According to their degree of cytotoxicity the compounds were divided in three groups: low, intermediate and high cytotoxicity. By observing the chemical structures of compounds belonging to the first group we can see that less cytotoxic activities are related to the presence of a 3β-hydroxy group on C-3 (ring A) and a double bond between C-22 and C-23 (side chain). The replacement of a 5α-hydroxy group by a 5α-fluoro group enhances cytotoxicity. Halogenated brassinosteroid derivatives in C-3 position are more cytotoxic than those with an acetoxy group in the same position. For compounds 1d, 6b, 10b and ribavirin, cytotoxicity measurements were also done with replicating cells; CC₅₀ values were low, but they still competed favourably with ribavirin against MV.

Reports on structural diversification of steroids by means of multicomponent reactions (MCRs) have significantly increased over the last decade. This review covers the most relevant strategies dealing with the use of steroidal substrates in MCRs, including the synthesis of steroidal heterocycles and macrocycles as well as the conjugation of steroids to amino acids, peptides and carbohydrates. We demonstrate that steroids are available with almost all types of MCR reactive functionalities, e.g., carbonyl, carboxylic acid, alkyne, amine, isocyanide, boronic acid, etc., and that steroids are suitable starting materials for relevant MCRs such as those based on imine and isocyanide. The focus is mainly posed on proving the amenability of MCRs for the diversity-oriented derivatization of naturally occurring steroids and the construction of complex steroid-based platforms for drug discovery, chemical biology and supramolecular chemistry applications.

The reaction of ergosterol (ERGO) with singlet oxygen in vitro was studied by using different combinations of the photosensitizers (i.e. rose Bengal and eosine) and solvents (i.e. pyridine, ethanol and methyl tert-butyl ether) and all the products obtained were isolated and fully characterized (mp, R_f, UV, ¹H-NMR, ¹³C-NMR, EI-MS, ESI-MS and HR-MS). In pyridine, together with the expected (22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol, EEP, the keto derivative (22E)-3β-hydroxyergosta-5,8(9),22-trien-7-one, KE, was obtained. In ethanol the expected EEP was obtained together with (22E)-5α,8α-epidioxyergosta-6,9,22-trien-3β-ol, EEP9(11), and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol, DHOE, as main products and (22E)-ergosta-5,7,9,22-tetraen-3β-ol, DHE, in trace amounts. In methyl tert-butyl ether, a complex mixture of EEP, KE, DHOE, EEP9(11), DHE, together with (22E)-7α-hydroperoxyergosta-5,8(9),22-trien-3β-ol, EHP, and (22E)-ergosta-5,8(9),22-triene-3β,7α-diol, EH, was obtained. The minor products were characterized and showed strong dependence on the reaction medium. The regioselective and stereoselective character of the singlet oxygen attack on the ERGO diene moiety is discussed in terms of ERGO HOMO's properties.