Cocrystallization improves the tabletability of ligustrazine despite a reduction in plasticity.

Cocrystallization is an effective method for altering the tableting performance of crystals by modifying their mechanical properties. In this study, cocrystals of ligustrazine (LIG) with malonic acid (MA) and salicylic acid (SA) were investigated to better understand how modifying crystal structure can affect tableting properties. LIG suffered from overcompression at high pressures despite its high plasticity. Both LIG-MA and LIG-SA displayed lower plasticity than LIG, which was confirmed by both an in-die Heckel and energy framework analyses. The LIG-MA cocrystal displayed slightly worse tabletability than LIG, as expected from its lower plasticity. However, LIG-SA surprisingly showed improved tabletability despite its lower plasticity. This was explained by the higher bonding strength of LIG-SA compared with LIG. This work not only provided new examples of tabletability modulation through crystal engineering but also highlighted the risk of failed tabletability predictions based on plasticity alone. Instead, more reliable tabletability predictions of different crystal forms must consider the bonding area - bonding strength interplay.

Improving the Physicochemical and Biopharmaceutical Properties of Active Pharmaceutical Ingredients Derived from Traditional Chinese Medicine through Cocrystal Engineering.

Active pharmaceutical ingredients (APIs) extracted and isolated from traditional Chinese medicines (TCMs) are of interest for drug development due to their wide range of biological activities. However, the overwhelming majority of APIs in TCMs (T-APIs), including flavonoids, terpenoids, alkaloids and phenolic acids, are limited by their poor physicochemical and biopharmaceutical properties, such as solubility, dissolution performance, stability and tabletability for drug development. Cocrystallization of these T-APIs with coformers offers unique advantages to modulate physicochemical properties of these drugs without compromising the therapeutic benefits by non-covalent interactions. This review provides a comprehensive overview of current challenges, applications, and future directions of T-API cocrystals, including cocrystal designs, preparation methods, modifications and corresponding mechanisms of physicochemical and biopharmaceutical properties. Moreover, a variety of studies are presented to elucidate the relationship between the crystal structures of cocrystals and their resulting properties, along with the underlying mechanism for such changes. It is believed that a comprehensive understanding of cocrystal engineering could contribute to the development of more bioactive natural compounds into new drugs.

Pesimquinolones produced by Penicillium simplicissimum and their inhibitory activity on nitric oxide production.

Eight undescribed quinolone alkaloids, pesimquinolones A-H, as well as six known compounds, were isolated from the solid culture broth of the fungus Penicillium simplicissimum. Their chemical structures were characterized by combined analyses of NMR spectroscopy and single-crystal X-ray crystallography. Pesimquinolones A-G are the first examples of naturally occurring quinolone alkaloids possessing a limonene moiety. Their anti-inflammatory activities on LPS-induced nitric oxide (NO) production in adherent cells were evaluated. Pesimquinolones A, E, G, and H showed promising suppressive effect on the production of NO with IC50 values of 1.94, 1.29, 1.20, and 1.23 µM, respectively.

Emeriones A-C: Three Highly Methylated Polyketides with Bicyclo[4.2.0]octene and 3,6-Dioxabicyclo[3.1.0]hexane Functionalities from Emericella nidulans.

Emeriones A-C (1-3), three highly methylated polyketides with bicyclo[4.2.0]octene and 3,6-dioxabicyclo[3.1.0]hexane functionalities, were isolated from Emericella nidulans. An additional peroxide bridge in compound 3 led to the construction of an unexpected 7,8-dioxatricyclo[4.2.2.02,5]decene scaffold. The structures of 1-3 were elucidated by comprehensive spectroscopic techniques, and their absolute configurations were confirmed by single-crystal X-ray crystallographic analyses and ECD calculations. Compound 1 shows weak inhibitory effects on NO production in LPS-induced RAW264.7 cells.

Butenolides from a marine-derived fungus Aspergillus terreus with antitumor activities against pancreatic ductal adenocarcinoma cells.

Chemical study on the extract of a marine-derived fungus Aspergillus terreus yielded twelve butenolide derivatives, including three new compounds, namely asperlides A-C (1-3) and nine known butenolides (4-12). The structures of 1-3 were confirmed by comprehensive spectroscopic analysis, including HRESIMS, NMR spectroscopy, and calculated electronic circular dichroism (ECD). The cytotoxicity of the compounds was evaluated using PANC-1, HCC1806, HepG2, BEAS-2B and HT-29 cancer cells. The results showed that (+)-3',3'-di-(dimethylallyl)-butyrolactone II (4) and versicolactone B (6) exhibited the most potent cytotoxin of PANC-1 cell line, with the IC50 values of 5.3 and 9.4 µM, respectively. Morphological features of apoptosis were observed in 4 and 6-treated PANC-1 cells, including apoptotic body formation, membrane blebbing, cell shrinkage and nuclear condensation. Cell cycle analysis with propidium iodide staining exhibited that 4 inhibits proliferation of PANC-1 cells via the induction of G2/M and S phase arrest, while 6 could retard the PANC-1 cells via the induction of S phase arrest. Flow cytometric analysis suggested that treatment with 4 and 6 significantly induced PANC-1 cells apoptosis. These findings indicated that 4 and 6 might serve as a starting point for the development of an anticancer drug for the treatment of pancreatic ductal adenocarcinoma.