Synthesis of New Brassinosteroid Analogs with Androstane Skeleton and Heterocyclic Acyl Side Chains: Preliminary Molecular Docking Studies

TL;DR

Scientists synthesized new brassinosteroid analogs with heterocyclic side chains and found some may have better biological activity than natural brassinolide.

Contribution

New brassinosteroid analogs with androstane skeletons and heterocyclic acyl side chains were synthesized and evaluated via molecular docking.

Findings

Analog 36 with an indole group forms a more stable complex with BRI1–BAK1 than brassinolide.

Derivative 23 with a benzoate function and F atom shows high binding energy and similar interactions.

Molecular docking suggests analogs like 36 may exhibit biological activity comparable to brassinolide.

Abstract

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.

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