Design, synthesis and anti-tumor efficacy evaluation of novel 1,3-diaryl propane-based polyphenols obtained from Claisen rearrangement reaction.

Polyphenols such as resveratrol, honokiol and nordihydroguaiaretic acid are widely existing in nature products or synthetic compounds with interesting biological activities. Inspired by their structural feature, a total of 49 1,3-diaryl propane-based polyphenols were designed and synthesized through Claisen rearrangement reaction. New compounds were initially assessed for their anti-proliferative activities against various cancer cell lines (PC-3, U87MG, U251, HCT116) at a concentration of 50 µM, and the results guided the SAR of this series of compounds. Further screening of selected compounds against seven cancer cell lines (three additional colon cancer cell lines namely COLO205, HT29 and SW480 were chosen) led to the identification of two advanced leads 2t and 3t with IC50 values ranging from 8.2 ± 0.1 to 19.3 ± 1.9 µM. Both compounds also showed promising anti-proliferative activities against COLO205 in dose- and time-dependent manners. Furthermore, 2t and 3t exhibited good anti-tumor efficacy in COLO205 xenografted mice model with TGI values ranging from 38% to 58%. These results warrant the further investigation of this series of compounds.

Design, synthesis and antitumor efficacy evaluation of a series of novel ß-elemene-based macrocycles.

ß-Elemene is the major constituent of the antitumor drugs elemene extract approved in China. By incorporating macrocyclization strategy into the ß-elemene skeleton, we designed a series of novel macrocycles retaining three key carbon-carbon double bonds. Four different methods have been successfully developed for these challenging ring systems. A total of twenty-eight 14- to 24-membered macrocycles were synthesized. Most of these macrocycles exhibited good antitumor activity against several cancer cell lines (PC-3, A549, U87MG, U251 and HCT116), with up to 40 folds improvement of activity comparing to ß-elemene. Additionally, X-ray single crystal structures of compounds Ic, Ip, and IIh were successfully solved as the proof of macrocycle formation. The results warrant the further investigation of this novel class macrocycles in pharmacokinetic and pharmacodynamics studies, which will be reported in due course.

Recent Progress in Fragmentation of Katritzky Salts Enabling Formation of C-C, C-B, and C-S Bonds.

Since their discovery in 1970s, Katritzky salts have emerged as one of the most important classes of building blocks for use in organic synthesis and drug discovery. These bulky pyridinium salts derived from alkylamine can readily generate alkyl radical and undergo a variety of organic transformation reactions such as alkylation, arylation, alkenylation, alkynylation, carbonylation, sulfonylation, and borylation. Through these transformations, complexed molecules bearing new C-C, C-B, or C-S bonds can be constructed in easy ways and in simple steps. This review aims to summarize recent advances in these versatile building blocks in well-classified categories. Representative examples and their reaction mechanisms are discussed. The hope is to provide the scientific community with convenient access to collective information and accelerate further research.

Recent Advances in Synergistic Antitumor Effects Exploited from the Inhibition of Ataxia Telangiectasia and RAD3-Related Protein Kinase (ATR).

As one of the key phosphatidylinositol 3-kinase-related kinases (PIKKs) family members, ataxia telangiectasia and RAD3-related protein kinase (ATR) is crucial in maintaining mammalian cell genomic integrity in DNA damage response (DDR) and repair pathways. Dysregulation of ATR has been found across different cancer types. In recent years, the inhibition of ATR has been proven to be effective in cancer therapy in preclinical and clinical studies. Importantly, tumor-specific alterations such as ATM loss and Cyclin E1 (CCNE1) amplification are more sensitive to ATR inhibition and are being exploited in synthetic lethality (SL) strategy. Besides SL, synergistic anticancer effects involving ATRi have been reported in an increasing number in recent years. This review focuses on the recent advances in different forms of synergistic antitumor effects, summarizes the pharmacological benefits and ongoing clinical trials behind the biological mechanism, and provides perspectives for future challenges and opportunities. The hope is to draw awareness to the community that targeting ATR should have great potential in developing effective anticancer medicines.

Races of small molecule clinical trials for the treatment of COVID-19: An up-to-date comprehensive review.

The coronavirus disease-19 (COVID-19) pandemic has become a global threat since its first outbreak at the end of 2019. Several review articles have been published recently, focusing on the aspects of target biology, drug repurposing, and mechanisms of action (MOAs) for potential treatment. This review gathers all small molecules currently in active clinical trials, categorizes them into six sub-classes, and summarizes their clinical progress. The aim is to provide the researchers from both pharmaceutical industries and academic institutes with the handful information and dataset to accelerate their research programs in searching effective small molecule therapy for treatment of COVID-19.

Nickel-catalyzed enantioselective 1,2-vinylboration of styrenes.

A novel nickel-catalyzed asymmetric 1,2-vinylboration reaction has been developed to afford benzylic alkenylboration products with high yields and excellent enantioselectivities by using a chiral bisoxazoline ligand. Under optimized conditions, a wide variety of chiral 2-boryl-1,1-arylvinylalkanes are efficiently prepared from readily available olefins and vinyl halides in the presence of bis(pinacolato)diboron as the boron source in a mild and easy-to-operate manner. This three-component cascade protocol furnishes exceptional chemo- and stereoselectivity, and its usefulness is illustrated by its application in asymmetric modifications of several structurally complex natural products and pharmaceuticals.

Establishment of predictive model for analyzing clinical pregnancy outcome based on IVF-ET and ICSI assisted reproductive technology.

In order to explore the predictive model for analyzing clinical pregnancy outcomes based on IVF-ET (in vitro fertilization and embryo transfer) and ICSI (Intracytoplasmic sperm injection) assisted reproductive technology (ART). METHODS: this study selected the embryo transfer (fresh) patients who received IVF-ET or ICSI treatment in the First Affiliated Hospital of Guangxi Medical University as the subjects. Moreover, the controlled ovarian stimulation (COS) and follow-up were conducted to collect relevant data for analysis, and finally a prediction model was established. RESULTS: The results showed that the patients were divided into different ovarian response groups at first. The age, bFSH and bFSH/bLH were the highest in the poor ovarian response group (POR), followed by the normal ovarian response group (NOR) and the lowest in the high ovarian response group (HOR). The area under the ROC curve was 0.669 according to the predictive model of pregnancy-related factors. The confidence interval of 94% was 0.629-0.697, with statistical significance (P = 0.000, P < 0.01). CONCLUSION: it can be concluded that in clinical pregnancy, for many related factors, regression equation can be used to establish a prediction model to diagnose the success rate of pregnancy. In conclusion, a prediction model can be built based on the relevant experimental results, to provide experimental reference ideas for increasing the success rate of ART in late clinical pregnancy, which is of great research significance.