Synthesis, biological evaluation, molecular docking studies and In-silico ADMET evaluation of pyrazines of pentacyclic triterpenes.

The semisynthesis of novel derivatives of lupeyl palmitate and 3ß-palmitoyloxy-olean-12-ene by introduction of a pyrazine at C-2 / C-3 and modifications of the relatively unexplored C-30 position of lupeol derivatives was conducted, and their cytotoxic and anti-inflammatory activities were evaluated. The derivatives 7, 10 and 11 significantly inhibited the tumor cell lines U251, K562, HCT-15, MCF-7 and SKLU-1, and compounds 7 and 11 were more active (IC50 25.4 ± 2.0 µM and 7.1 ± 0.4 µM, respectively) than the positive control (etoposide (IC50 31.5 ± 2.2 µM) in the tumor line PC-3. Introduction of the pyrazine at C-2 / C-3 in compounds 1 and 2 or modification at C-30 of compound 1 decreased the anti-inflammatory activity in the TPA-induced mouse ear edema. Following the results of the PASS online evaluation of the potential biological activity of the natural compounds and their derivatives, the inhibition of pNF-κB translocation to the prostate cancer (PC-3) cell nucleus was investigated and the binding mode of compounds 7, 10 and 11 with the human NF-κB receptor was explored by a molecular docking study. These derivatives bound directly or close to the amino acids that form the DNA recognition site. The ADMET physicochemical parameters of the fifteen compounds were further analyzed in silico using Molinspiration calculations indicating the potential of compounds 7, 10 and 11 for further investigation.

Structural Reassignment of rel-(3'Z,3R,6R,7R,3a'R,6'R)-3,8-Dihydrodiligustilide and the Activity of Diligustilide and 3,8-Dihydro- and 3,8,7',7a'-Tetrahydrodiligustilides as Progestins.

Several phthalides were semisynthesized, including a 3,8-dihydrodiligustilide with progesterone-like activity, previously isolated from Ligusticum chuanxiong, the structure of which was earlier assigned to a semisynthetic product with nonidentical spectroscopic constants. The structure of this natural phthalide was reassigned with a proposal of its absolute configuration. Phthalides acted as progestins in cell viability assays, immunofluorescence microscopy, and docking analysis. Therefore, the structures for natural and semisynthetic phthalides with potential use in hormone-related therapies were reassigned.