Fusicoccane Diterpenes from Hypoestes forsskaolii as Heat Shock Protein 90 (Hsp90) Modulators

Abstract

Ten new (1–10) and six known (11–16) fusicoccane diterpenes were isolated from the roots of Hypoestes forsskaolii. The structural characterization of 1–10 was performed by spectroscopic analysis, including 1D and 2D NMR, ECD, and HRESIMS experiments. From a perspective of obtaining potential Hsp90α inhibitors, the isolates were screened by surface plasmon resonance measurements and their cytotoxic activity was assayed using Jurkat and HeLa cancer cells. Compound 6, 18-hydroxyhypoestenone, was shown to be the most active compound against Hsp90, and its interactions were studied also by biochemical and cellular assays and by molecular docking.

Long-Lasting Anti-Inflammatory and Antinociceptive Effects of Acute Ammonium Glycyrrhizinate Administration: Pharmacological, Biochemical, and Docking Studies

“…First, all missing hydrogen atoms were added, bond orders were properly assigned, partial charges calculated, water molecules were eliminated, and protein termini were capped. Glycyrrhizic acid was built with Maestro’s Build Panel (Maestro version 10.2, 2015), processed with LigPrep (LigPrep version 3.4, 2015) and, finally, minimized with the OPLS 2005 force field [76].…”

Evaluation of Antidiabetic and Antioxidant Activity of Leaf Extract and Solvent Fractions of Hypoestes forskaolii (Val) (Acanthaceae) in Mice

“…8,9 Of the phytochemical compounds identified, fusicoccane Diterpene compounds were previously isolated from the methanol root extract, and it has verified antioxidative and cytotoxic and genotoxic activities. 10 To the best of the authors' knowledge, there are no previous scientific reports on the antidiabetic activity of H. forskaolii. Therefore, this study aimed evaluation of antidiabetic and antioxidant activity of leaf extract and solvent fractions of hypoestes forskaolii (Val) (Acanthaceae) in mice.…”

A Two‐Phase Approach to Fusicoccane Synthesis To Uncover a Compound That Reduces Tumourigenesis in Pancreatic Cancer Cells

“…To examine divergence of “core” intermediate 3 towards C18‐α‐Me fusicoccanes, we chose 3(11)‐epoxyhypoestenone ( 2 ) as our target molecule. 3(11)‐Epoxyhypoestenone ( 2 ) was recently isolated from Hypoestes forsskaolii [3g] and Hypoestes verticillaris , [17] respectively and was reported to exhibit strong Hsp90α binding affinity [3g] . Structurally, it features a transannular oxa‐bridge.…”

“…Our group has a long‐standing interest in preparing sesquiterpenoids, diterpenoids, and their derivatives for anticancer medical purposes [16] . During the course of our efforts to develop a versatile platform for the synthesis of fusicoccane diterpenes, we accomplished the first total synthesis of alterbrassicicene D [2g] ( 1 ) and 3(11)‐epoxyhypoestenone ( 2 ) [3g, 17] . Herein, we report the initial results from these efforts, which resulted in unambiguous structural determination of 2 , and provided materials for preliminary anticancer evaluation.…”