An Efficient Regioselective Synthesis of 8-Formylhomoisoflavonoids with Neuroprotective Activity by Enhancing Autophagy.

6-Formylisoophiopogonone B (7a) and 8-formylophiopogonone B (7b), two natural products isolated from Ophiopogon japonicus, represent a subgroup of rare 6/8-formyl/methyl-homoisoflavonoid skeletons. Herein we report an efficient method for the synthesis of these formyl/methyl-homoisoflavonoids. The synthesized compounds were evaluated for their neuroprotective effects on the MPP+-induced SH-SY5Y cell injury model and showed marked activity. Exploration of the neuroprotective mechanisms of compound 7b led to an increased expression of autophagy marker LC3-II and down-regulation of autophagy substrate p62/SQSTM1. Molecular docking studies showed that 7b may prevent the inhibition of the classic PI3K-AKT-mTOR signaling pathway by interfering with the human HSP90AA1.

New homoisoflavonoid analogues protect cells by regulating autophagy.

As a special group of naturally occurring flavonoids, homoisoflavonoids have been discovered as active components of several traditional Chinese medicines for nourishing heart and mind. In this study, twenty homoisoflavonoid analogues, including different substitution groups on rings A and B, as well as heteroaromatic B ring, were synthesized and evaluated for their cardioprotective and neuroprotective activities. In a H2O2-induced H9c2 cardiomyocytes injury assay, nine homoisoflavonoid analogues showed promising activities in the same level as the positive control, diazoxide. Six cardioprotective compounds with representative structure diversities were then evaluated for their neuroprotective effects on MPP+ induced SH-SY5Y cell injury model. Furthermore, autophagy inducing monodansylcadaverine (MDC) fluorescence staining methods and molecular docking studies indicated the action mechanism of these compounds may involve autophagy regulating via class I PI3K signaling pathway.

Design, synthesis, and antimicrobial activities of new tanshinone IIA esters.

Sixteen new ester derivatives with various partition coefficient (ClogP) values of tanshinone IIA (TSIIA), a major lipophilic component of Salvia miltiorrhiza, were designed and synthesised, including six aliphatic esters (3a-e, 5a), one phosphate ester (4c) and nine aromatic esters (5b-j). Their antimicrobial activities against three Gram-positive bacteria strains, Staphylococcus aureus, Bacillus subtilis, and Bacillus amyloliquefaciens, and two Gram-negative bacteria strains, Pseudomonas aeruginosa and Escherichia coli, as well as two fungi species, Candida albicans and Saccharomyces cerevisiae, were evaluated in vitro by broth microdilution susceptibility tests. The results showed that keeping ClogP values in a certain range is necessary for their antimicrobial activities. For those compounds with ClogP values between 5 and 10, their MIC values showed positive correlations with ClogP values. In particular, compound 3e exhibited fourfold and twofold higher potency than the standard drug amphotericin B against fungi C. albicans and S. cerevisiae with MIC values of 1.95 and 7.81 µg/mL, respectively.