Much work has been dedicated to the quest to determine the structure–activity relationship in synthetic brassinosteroid (BR) analogs. Recently, it has been reported that analogs with phenyl or benzoate groups in the alkyl chain present activities comparable to those shown by natural BRs, depending on the nature of the substituent in the aromatic ring. However, as it is well known that the activity depends on the structure of the whole molecule, in this work, we have synthesized a series of compounds with the same substituted benzoate in the alkyl chain and a hydroxyl group at C3. The main goal was to compare the activities with analogs with -OH at C2 and C3. Additionally, a molecular-docking study and molecular dynamics simulations were performed to establish a correlation between the experimental and theoretical results. The synthesis of eight new BR analogs was described. All the analogs were fully characterized by spectroscopical methods. The bioactivity of these analogs was assessed using the rice lamina inclination test (RLIT) and the inhibition of the root and hypocotyl elongation of Arabidopsis thaliana. The results of the RLIT indicate that at the lowest tested concentration (1 × 10⁻⁸ M), in the BR analogs in which the aromatic ring was substituted at the para position with methoxy, the I and CN substituents were more active than brassinolide (50–72%) and 2–3 times more active than those analogs in which the substituent group was F, Cl or Br atoms. However, at the highest concentrations, brassinolide was the most active compound, and the structure–activity relationship changed. On the other hand, the results of the A. thaliana root sensitivity assay show that brassinolide and the analogs with I and CN as substituents on the benzoyl group were the most active compounds. These results are in line with those obtained via the RLIT. A comparison of these results with those obtained for similar analogs that had a hydroxyl group at C2 indicates the importance of considering the whole structure. The molecular-docking results indicate that all the analogs adopted a brassinolide-like orientation, while the stabilizing effect of the benzoate group on the interactions with the receptor complex provided energy binding values ranging between −10.17 and −13.17 kcal mol⁻¹, where the analog with a nitrile group was the compound that achieved better contact with the amino acids present in the active site.

Brassinosteroid analogs with heterocyclic rings in the side chain are interesting because important biological activity has been shown by these compounds. Thus, herein, five 23-24-dinorcholane BR analogs with a heterocyclic ester function at C-22 were synthesized and fully characterized by different spectroscopic techniques. The acylation reaction at C-22, which is a key synthetic step, was carried out by two different methods, namely acylation with heterocyclic acid chlorides and Steglich esterification reaction. In both cases, the acyl derivatives were obtained with good yields. Additionally, a preliminary molecular docking study of BRI1–BAK1 complexes formed by these analogs and brassinolide was performed to estimate what their biological activity would be. Results indicate that the complex formed by the analog 36, which has an indole group in the side chain, within the active site of BRI1–BAK1 is more stable than that formed by brassinolide. Additionally, molecular docking of a derivative having a benzoate function at C-22 and a F atom in the ortho position, 23, shows a similar pose and interactions at the active site but the highest binding energy. As 23 has shown similar activity to brassinolide in the Rice Lamina Inclination Test, it is expected that 36 will also exhibit similar behavior.

Herein, a new series of 3-DT analogs with benzoylated groups at C-23 are synthesized and characterized. The benzoylated groups carry the same substituents in the ortho- or para-positions. Thus, the effect of structure on activity, measured using the rice lamina inclination test (RLIT) and the bean second-internode assay (BSI), is evaluated. The RLIT results indicate that a benzoylate function at C-22 induces a strong increase in activity that depends on the position and nature of the substituent in the phenyl ring. For example, an analog with an -OAc group in the ortho-position is the most active derivative, and its activity is like that of brassinolide. A relative index is calculated using brassinolide as a positive control to compare the RLIT results with those reported previously. This analysis allows for the conclusion that benzoylated derivatives with a hydroxyl group at C-3 are much more active than the corresponding analogs with a carbonyl group in this position, and one extra alcohol group in the alkyl chain decreases RLIT activity. Finally, the results obtained with the BSI are clearly different to those obtained in the RLIT bioassay. Therefore, the application of any activity–structure relationship will always be dependent on the bioassay used to determine activity.

Recent studies have demonstrated the antiproliferative and cytotoxic effects of aza-steroids and steroidal sapogenins on human cancer cell lines. The scientific community has shown a growing interest in these compounds as drug candidates for cancer treatment. In the current work, we report the synthesis of new diosgenin oxime derivatives as potential antiproliferative agents. From (25 R)-5α-spirost-3,5,6-triol (1), a diosgenin derivative, ketones 2, 3, 4, and 9 were obtained and used as precursors of the new oximes. A condensation reaction was carried out between the steroidal ketones (2, 3, 4, and 9) with hydroxylamine hydrochloride in 2,4,6-trimethylpyridine to produce five spirostanic oximes (four of them are not reported before) with a 42–96% yield. Also, a new spirostanic α, β-unsaturated cyanoketone was synthesized via Beckmann fragmentation using thionyl chloride with a 62% yield. Furthermore, we proposed a reaction mechanism with the aim of explaining such transformation.