Design, Synthesis and Cytotoxicity Evaluation of Novel Indole Derivatives Containing Benzoic Acid Group as Potential AKR1C3 Inhibitors.

Castration-resistant prostate cancer (CRPC) is a fatal, metastatic form of prostate cancer, characterized by reactivation of the androgen axis. Aldo-keto reductase 1C3 (AKR1C3) converts androstenedione (AD) and 5α-androstanedione to testosterone (T) and 5α-dihydrotestosterone (DHT), respectively. In CRPC, AKR1C3 is upregulated and implicated in drug resistance and has been regarded as a potential therapeutic target. Here we examined a series of indole derivatives containing benzoic acid or phenylhydroxamic acid and found that 4-({3-[(3,4,5-trimethoxyphenyl)sulfanyl]-1H-indol-1-yl}methyl)benzoic acid (3e) and N-hydroxy-4-({3-[(3,4,5-trimethoxyphenyl)sulfanyl]-1H-indol-1-yl}methyl)benzamide (3q) inhibited 22Rv1 cell proliferation with IC50 values of 6.37 µM and 2.72 µM, respectively. In enzymatic assay, compounds 3e and 3q exhibited potent inhibitory effect against AKR1C3 (IC50 =0.26 and 2.39 µM, respectively). These results indicated that compounds 3e and 3q might be useful leads for further investigation of more potential AKR1C3 inhibitors used for CRPC.

Three new sesquiterpene lactones from the whole plants of Elephantopus scaber.

Three new sesquiterpene lactones, named scabertopinolides H - J (1 - 3), along with four known ones, desacylisodeoxyelephantopin 2-methylbutyrate (4), iso-17,19-dihydrodeoxyelephantopin (5), scabertopinolide D (6) and (2R,6R,7R,8S)-8-tigloyloxy-1(10),4(5),11(13)-germacratrien-2,15,6,12-diolide (7) were isolated from the whole plants of Elephantopus scaber. Their structures were elucidated by extensive analysis of spectroscopic data (including IR, UV, HRESIMS, 1 D and 2 D NMR) and single-crystal X-ray. These isolated compounds showed effective anti-inflammatory effects on LPS-stimulated RAW 264.7 cells with IC50 values of 6.27 ± 0.18 to 18.31 ± 1.38 µM.

Crassifolins Q-W: Clerodane Diterpenoids From Croton crassifolius With Anti-Inflammatory and Anti-Angiogenesis Activities.

Seven new clerodane diterpenoids, crassifolins Q-W (1-7), along with five known analogues (8-12), were isolated from the roots of Croton crassifolius. Their structures were identified by comprehensive spectroscopic analysis (UV, IR, NMR, and HR-ESI-MS), and their absolute configurations were determined by ECD spectra and X-ray crystallography. The activities of compounds 1-5 against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were assessed, and compound 5 showed the most significant activity with the secretion levels of IL-6 and TNF-α at 32.78 and 12.53%, respectively. Moreover, compounds 1-5 were screened for their anti-angiogenesis using a human umbilical vein endothelial cells in vitro mode; the results showed all of them exhibited obvious anti-angiogenesis activities, in particular, compound 5 showed the strongest anti-angiogenesis effect in the range of 6.25-50 µM.

Five matrine-type alkaloids from Sophora tonkinensis.

Five matrine-type alkaloids (1‒5) including two new compounds (1 and 3) and a new natural product (2) were isolated from the roots of Sophora tonkinesis. Their structures were identified by extensive spectroscopic analysis (UV, IR, HRESIMS and NMR). The absolute configurations of 2 and 3 were determined by X-ray diffraction. Compounds 1‒5 were evaluated their activity against inflammatory cytokines TNF-α and IL-6 levels on LPS-induced RAW 264.7 macrophages, and compound 1 showed the most significant activity, potent than that of matrine, the representative ingredient from Sophora plants.