Eight triflavonoids, selagintriflavonoids A-H, were isolated from whole herbs of Selaginella doederleinii. The structures of compounds selagintriflavonoids A-C consisted of three naringenin units, whereas those of selagintriflavonoids D-H consisted of apigenin and two naringenin moieties. The structures and absolute configurations of the compounds were determined based on NMR, HRESIMS, and experimental and calculated electronic circular dichroism (ECD) data. The ability of the compounds to inhibit β-secretase (BACE1) was also evaluated. All compounds exhibited BACE1 inhibition with IC50 values ranging from 0.75 to 46.99 μM. Selagintriflavonoid A exhibited the strongest inhibition (0.75 μM) and is thus a promising compound for treating Alzheimer's disease.

Five new carboxymethyl flavonoids named 5-carboxymethyl-3′, 4′, 7-trihydroxyflavone (1), (2S)- 5-carboxymethyl-3′, 4′, 7-trihydroxyflavonone (2a), (2R)-5-carboxymethyl-3′, 4′, 7-trihydroxyflavonone (2b), (2S)-5-carboxymethyl-4′, 7-dihydroxyflavonone (3), 5- carbomethoxymethyl-4′, 7-dihydroxyflavone (4), and a new chromone named 5-carboxymethyl-7-hydroxychromone (5), together with two known compounds 5-carboxymethyl-4′-hydroxyflavone-7-O-β-d-glucopyranoside (6), 5-carboxymethyl-4′, 7-dihydroxyflavone (7) were isolated from Selaginella moellendorffii Hieron. Their structures including absolute configuration were elucidated by extensive spectroscopic methods and experimental electronic circular dichroism (ECD) spectra. What's worth mentioning is that a carboxymethyl substituent appeared at the C-5 position of all isolated compounds, only recently discovered in genus Selaginella. Compounds 2a and 2b were identified as a pair of chiral isomers; compound 5 was discovered as the first chromone comprising a carboxymethyl side chain. Furthermore, all compounds were evaluated for their antibacterial activities against various Gram-positives and Gram-negatives, and compared to the reference drugs amoxicillin and norfloxacin. As a result, compounds 3 and 4 exhibited as potent antimicrobial agents with a broad spectrum, and compound 5 appeared as the most promising one to combat Gram-positives.

The overproduction of cortisol is associated with many severe and life-threatening diseases, such as Cushing's syndrome (CS) and chronic wound healing. 11β-Hydroxylase (CYP11B1) is considered as an attractive target for treating these diseases, since it is a key enzyme responsible for the last step in cortisol biosynthesis. Nowadays, medical therapy has become increasingly important for CS patients, especially for those who are in need of surgery or suffer from surgery failure and those in early phases of radiation therapy. In clinic, steroidogenesis blockers including CYP11B1 inhibitors are utilized most frequently. Nevertheless, drugs that inhibit CYP11B1 are inevitable with side effects due to lack of selectivity over other steroidogenesis enzymes. Recent advances in the development of novel CYP11B1 inhibitors might overcome these limitations. In addition, the beneficial effects of down-regulation of cortisol levels to wound closure have been recently disclosed and have stimulated topical application of CYP11B1 inhibitors as a novel therapeutic strategy for curing chronic wounds. Herein, we provide a review of the current CYP11B1 inhibitors in clinic combating CS and the latest development of novel CYP11B1 inhibitors for treating CS and chronic wounds.

Twenty-eight novel 1,5-disubstituted-2(1H)-pyridone derivatives were designed and synthesized for discovering more potent anti-lung cancer agents combined with anti-fibrotic profiles. The in vitro antiproliferative activities of the derivatives against A549 and NIH3T3 cell lines were tested by MTT assays. The majority of the tested analogues exhibited equivalent or an improved anti-lung cancer activity. Prominently, compound 4l displayed the best potency and selectivity toward A549 with an IC50 value of 20μM, nearly comparable to the positive control cisplatin (IC50=10μM) and even superior to the lead compound 22 (IC50=130μM). Simultaneously, compound 4l showed significant inhibitory activity against NIH3T3 (IC50=55μM), which may contribute to hindering the proliferation of lung cancer cells fundamentally. What is more, the 3D-QSAR models established on the activity data may provide new insights into the design of novel 2(1H)-pyridone derivatives and lay a theoretical foundation for further studies of promising anti-lung cancer activity with the maintenance of anti-fibrotic effect.

ABSTRACT CBR703 was reported to inhibit bacterial RNA polymerase (RNAP) and biofilm formation, considering it to be a good candidate for further optimization. While synthesized derivatives of CBR703 did not result in more-active RNAP inhibitors, we observed promising antibacterial activities. These again correlated with a significant cytotoxicity toward mammalian cells. Furthermore, we suspect the promising effects on biofilm formation to be artifacts. Consequently, this class of compounds can be considered unattractive as antibacterial agents.

Topical application of CYP11B1 inhibitors to reduce cutaneous cortisol is a novel strategy to promote healing of chronic wounds. Pyridyl substituted arylsulfonyltetrahydroquinolines were designed and synthesized resulting in a strong inhibitor 34 (IC50 = 5 nM). It showed no inhibition of CYP17 and CYP19 and no mutagenic effects. It exhibited inverse metabolic stability in plasma (t1/2 ≫ 150 min), which is similar to wound fluid in composition, and in liver S9 fractions (t1/2 = 16 min).

Weixing Zhu, Jörg Haupenthal, Matthias Groh, Michelle Fountain and Rolf W. 4 Hartmann* [a, b] 5 [a] Helmholtz Institute for Pharmaceutical Research Sa arland (HIPS), Department of Drug Design 6 and Optimization and [b] Pharmaceutical and Medicinal Chemistry, Saarland U iversity, Campus 7 C2_3, D-66123 Saarbrücken, Germany. [c] Helmholtz Centre for Infection Research, 8 Inhoffenstraße 7, Braunschweig 38124, Germany. 9 10

Chasing the active impurity: In the validation of a screening hit it was discovered that a polymeric trace impurity was responsible for the biological activity. Such a side product can be formed with similar compounds. During the investigations it was discovered that the negatively charged macromolecule interacts very efficiently with the protein surface of E. coli RNAP via electrostatic interactions.

Twenty‐seven 1,5‐disubstituted‐pyridin‐2(1H)‐one derivatives were synthesized and evaluated for their anti‐cancer and anti‐fibrosis activity by A549 and NIH3T3 cell viability assays, respectively. To study the selectivity between the cancer and fibrosis cell lines, pharmacophore models (F1–F4) were built in advance for compounds with pyridin‐2(1H)‐one scaffold, which revealed the relationship between the occupation of the aromatic sub‐site F4 and potent anti‐cancer activity. The relationship between structure and anti‐cancer activity for all target compounds is also reported herein: 1‐Phenyl‐5‐((m‐tolylamino)methyl)pyridine‐2(1H)‐one (22) displayed both potency and selectivity (IC50 = 0.13 mM) toward the A549 cell line through the inhibition of translation initiation, especially by eIF3a suppression, and can be treated as a lead for the design of novel eIF3a regulators and anti‐lung cancer agents.